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Nickel oxide nanoparticles induce cytotoxicity, oxidative stress and apoptosis in cultured human cells that is abrogated by the dietary antioxidant curcumin
... Nickel nanoparticles (NiNPs) are used in catalysts for hydrogenation of dietary fats, in cosmetics, insecticides, preparations for theranostics in medicine [1][2][3][4], and can also expose people occupationally in the metallurgy and mining industry [5]. According to multiple studies, in vitro NiNPs possess pro-oxidant, pro-inflammatory, genotoxic and carcinogenic activity [6][7][8]. At inhalation or intratracheal instillation in experimental animals, different adverse effects of Ni-containing NPs have been detected including general toxicity, immunotoxicity and reproductive toxicity [9]. ...
... Ten groups of 12 male Wistar rats received a balanced semisynthetic diet (AIN93M) either without additions (Control group 1), or supplemented with Ni carbonate basic salt (Ni salt) at doses of 0.1, 1 and 10 mg/kg b.w. as Ni (groups 2-4), NiNPs preparation 1 (NiNP1) (groups [5][6][7] or NiNPs preparation 2 (NiNP2) (groups 8-10) at the same doses as Ni, respectively, for 92 days. At the end of the feeding period, biochemical, immunological and morphological endpoints were studied. ...
... (NiNP1) (groups [5][6][7] or NiNPs preparation 2 (NiNP2) (groups 8-10) at the same doses as Ni, respectively, for 92 days. At the end of the feeding period, biochemical, immunological and morphological endpoints were studied. ...
... Nanomaterials can be easily absorbed and react with the vital organs (Shaw and Handy, 2011). Nickel oxide NPs (NiO-NPs) are one of the most utilized NPs in a variety of consumer goods such as solid oxide fuel cells, nanowires, catalysts, electrochromic coatings, ceramics, sensors, paints, and storage batteries (Mu et al., 2011), (Siddiqui et al., 2012). The increasing application of NiO-NPs has led to an increase in the environmental load and a dangerous hazard to human and animal health (Cao et al., 2016). ...
... Recently, NiO-NPs are used in many industrial and biomedical fields (Mu et al., 2011), (Siddiqui et al., 2012). Occupational exposure to NiO-NPs could cause inflammation and injury to multiple organs and tissues (Phillips et al., 2010). ...
Background: Nickel oxide nanoparticles (NiO-NPs) have recently been utilized in various advanced industrial fields like lithium-ion micro batteries, nanofibers, electrochromic devices, and several biomedical applications. NiO-NPs are classified as extremely toxic substances as they can cause long-term harm to the environment and aquatic life. Moreover, frequent and prolonged exposure can affect human and animal health, causing skin allergies and major toxic consequences, such as hepatorenal toxicity. Hesperidin (HSP) has been proven to possess anti-inflammatory, antioxidant, and free radical scavenging activities.
Objective: This study aimed to investigate the underlying protective mechanisms and effects of HSP against NiO-NPs-induced hepatorenal toxicities in rats.
Materials and Methods: Forty male Wistar rats were randomly divided into four groups (n = 10 in each). The first group served as a Control group. For 8 weeks, the second group was administered NiO-NPs (100 mg/kg/day), and the third group was given HSP (100 mg/kg/day) via oral gavage for both groups. The fourth group received NiO-NPs and HSP concurrently in the same oral daily doses and duration as the second and third groups.
Results: NiO-NPs administration revealed a significant increase in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (ALT, AST) in NiO-NPs group compared to Control group ( p < 0.05). In addition, NiO-NPs administration resulted in a substantial increase in malondialdehyde levels with a significant drop in catalase activity and GSH content in Group II. Also, a significant decreased expression of Nrf-2 and Bcl-2 mRNA levels and upregulation of TNF-α, NF-kβ and BAX in the liver and kidney of NiO-NPs group were also detected. Histologically, the liver and kidney of rats of NiO-NPs group showed significant histopathological disturbances, with a substantial increase in the proliferating cell nuclear antigen (PCNA) positive hepatocytes and renal tubular cells in the NiO-NPs group compared to Control and HSP groups ( p < 0.05). In contrast, concomitant administration of HSP with NiO-NPs in group IV showed a significant biochemical, histopathological, and immunohistochemical improvement compared to NiO-NPs group.
Conclusion: Co-administration of HSP with NiO-NPs significantly ameliorated most of the NiO-NPs-induced hepatorenal toxicities in male rats.
... It is proven that released Ni can store up in the human body reaching 20 to 1000 µM [27], so all these concentrations used for further study are all within ambient or in vivo concentrations, and even less than concentrations that can be attained in vivo [28]. Data suggested the LC 50 of Ni in MCF-7 cells, Hep-2 cells, and HepG2 cells range from 10 to 100 µg/mL [22,29], which revealed that HCEC were relatively sensitive to Ni compared to other cell species. Given that, exploring Ni-induced cytotoxicity of human corneal epithelial cells is needed. ...
... Evidence suggests that Ni and its compounds can be dissolved or acidified in cells, then produce superoxide anion free radicals and lipid peroxidation, which are considered to work in disrupting the activities of various antioxidant enzymes in cells, they directly stimulate cells to produce ROS. Eventually, these reactions lead to oxidative damage [22,33]. ...
Nickel (Ni) is ubiquitous in the environment and evidence has suggested that Ni can cause ocular surface inflammation, especially in fine particulate matter and personal products. Continuous daily exposure to Ni-containing dust may adversely impact the human cornea, whereas the un-derlying mechanism of this phenomenon remains not fully understood. Here, human corneal epithelial cells (HCEC) were employed to analyze the toxicity of Ni via detections of cell mor-phology, cell viability, reactive oxygen species production, cell apoptosis rate, and apoptotic gene expression levels after exposure for 24 h to uncover the damage of Ni to the cornea. A concentra-tion-dependent inhibition of HCECs’ viability and growth was observed. In particular, Ni at 100 μM significantly decreased cell viability to 76%, and many cells displayed an abnormal shape and even induced oxidative damage of HCEC by increasing ROS to 1.2 times, and further led to higher apoptosis (24%), evidenced by up-regulation of apoptotic genes Caspase-8, Caspase-9, NF-κB, IL-1β, and Caspase-3, posing a risk of dry eye. Our study suggested that Ni induces apoptosis of HCEC through oxidative damage. Therefore, Ni pollution should be comprehensively considered in health risks or toxic effects on the ocular surface.
... Moreover, it has been suggested that NPs induce oxidative stress that leads to DNA damage and apoptosis [63]. Siddiqui et al. (2012) [64] found that NiO-NPs increased apoptosis in MCF-7 and HEp-2 cells in vitro. The inhibition of APOX activities in the study might be an outcome of structural alterations of proteins, damage, and finally deactivation of the enzymes [65][66][67]. ...
... Moreover, it has been suggested that NPs induce oxidative stress that leads to DNA damage and apoptosis [63]. Siddiqui et al. (2012) [64] found that NiO-NPs increased apoptosis in MCF-7 and HEp-2 cells in vitro. The inhibition of APOX activities in the study might be an outcome of structural alterations of proteins, damage, and finally deactivation of the enzymes [65][66][67]. ...
The present study evaluates the effect of nickel oxide nanoparticles on some biochemical parameters and midgut tissues in the ground beetle Blaps polychresta as an indicator organism for nanotoxicity. Serial doses of the NiO-NPs colloid (0.01, 0.02, 0.03, 0.04, 0.05, and 0.06 mg/g) were prepared for injecting into the adult beetles. Insect survival was reported daily for 30 days, and the sublethal dose of 0.02 mg/g NiO-NPs was selected for the tested parameters. After the treatment, nickel was detected in the midgut tissues by X-ray microanalysis. The treated group demonstrated a significant increase in aspartate ami-notransferase (AST) and alanine aminotransferase (ALT) activities when compared to the untreated group. However, the treated group demonstrated a significant decrease in ascor-bate peroxidase (APOX) activity when compared to the untreated group. Histological and ultrastructural changes in the midgut tissues of treated and untreated beetles were also observed. The current findings provide a precedent for describing the physiological and his-tological changes caused by NiO-NPs in the ground beetle B. polychresta.
... Exposure to nickel causes a variety of toxic effects on cells, animals, and humans [22,[26][27][28]. Studies showed that nickel inhibits the proliferation of several kinds of cells. ...
... These results indicated that autophagy seems to be a survival mechanism, protecting thyroid cells from Ni 2+ mediated apoptosis. Apoptosis is the major form of cell death induced by NiSO 4 , this is consistent with other studies that Ni 2+ -induced apoptosis in NIH/3T3 cells, human bronchoalveolar carcinoma A549 cells, human airway epithelial HEp-2 cells, and human breast cancer MCF-7 cells [26,27,29]. Recently, it has been reported that excess iodine suppressed the expression of autophagy-related proteins and promoted the expression of apoptosis-related proteins in human thyroid follicular epithelial cells [20]. ...
Nickel is an industrial and environmental toxic metal, which is toxic to humans in certain forms at high doses. Here, we investigated the cytotoxic effects of nickel sulfate (NiSO4) exposure on the human thyroid follicular epithelial cells (Nthy-ori 3-1) and its underlying toxicological mechanisms. The results showed that NiSO4 reduced the cell viability of Nthy-ori 3-1 cells in a dose- and time-dependent manner, inducing S and G2/M phases cell-cycle arrest and apoptosis. Electron microscopy demonstrated that abundant autophagic vacuoles were found in Nthy-ori 3-1 cells after NiSO4 treatment. Accordingly, exposure of Nthy-ori 3-1 cells to NiSO4 resulted in a dose-dependent increase of LC3II/I ratio, an induction of Beclin-1 expression, and a decrease in p62 levels. Blockade of autophagy with 3-methyladenine (3-MA) potentiated the NiSO4-induced apoptotic cell death, while induction of autophagy significantly alleviated toxicity of NiSO4. From a molecular standpoint, NiSO4 markedly promoted the activation of p38 and IKKβ by increasing their phosphorylation. In conclusion, we showed that autophagy was induced to protect thyroid cells from Ni²⁺ mediated apoptosis, thus providing rational strategy to prevent against nickel toxicity in the thyroid.
... Intracellular (biotic) ROS can have origin in the endoplasmic reticulum, peroxisomes and in electron transport processes in mitochondria and chloroplasts (in eukaryotic photosynthetic organisms) (Lesser 2006; del Rio and Lopez-Huertas 2016) (Fig. 1E, bottom). MOx NPs, even containing redoxinactive metals, such as NiO (Siddiqui et al. 2012;Ahamed et al. 2013;Oukarroum et al. 2017;Sousa et al. 2018c;Sousa et al. 2018b) and ZnO NPs (De Berardis et al. 2010;Kumar et al. 2011;Alarifi et al. 2013;Lu et al. 2015;Ng et al. 2017) can induce intracellular ROS and oxidative stress. It was shown that P. subcapitata algal cells exposed to NiO NPs presented a reduced activity of the photosystem II (ɸPSII) and a decreased electron flow in the electron transport chain (ETC). ...
... The sequence of events associated with the induction of cell death in S. cerevisiae by NiO NPs was described (Sousa et al. 2019c). Other studies also indicated a cell dead apoptotic pathway in human cell lines exposed to CuO (Siddiqui et al. 2013), NiO (Siddiqui et al. 2012), ZnO (Keerthana and Kumar 2020), or binary mixtures of Al 2 O 3 and ZnO NPs (Koerich et al. 2020). ...
The incorporation of nanomaterials (NMs), including metal(loid) oxide (MOx) nanoparticles (NPs), in the most diversified consumer products, has grown enormously in recent decades. Consequently, the contact between humans and these materials increased, as well as their presence in the environment. This fact has raised concerns and uncertainties about the possible risks of NMs to human health and the adverse effects on the environment. These concerns underline the need and importance of assessing its nanosecurity. The present review focuses on the main mechanisms underlying the MOx NPs toxicity, illustrated with different biological models: release of toxic ions, cellular uptake of NPs, oxidative stress, shading effect on photosynthetic microorganisms, physical restrain and damage of cell wall. Additionally, the biological models used to evaluate the potential hazardous of nanomaterials are briefly presented, with particular emphasis on the yeast Saccharomyces cerevisiae, as an alternative model in nanotoxicology. An overview containing recent scientific advances on cellular responses (toxic symptoms exhibited by yeasts) resulting from the interaction with MOx NPs (inhibition of cell proliferation, cell wall damage, alteration of function and morphology of organelles, presence of oxidative stress bio-indicators, gene expression changes, genotoxicity and cell dead) is critically presented. The elucidation of the toxic modes of action of MOx NPs in yeast cells can be very useful in providing additional clues about the impact of NPs on the physiology and metabolism of the eukaryotic cell. Current and future trends of MOx NPs toxicity, regarding their possible impacts on the environment and human health, are discussed.
Key points
• The potential hazardous effects of MOx NPs are critically reviewed.
• An overview of the main mechanisms associated with MOx NPs toxicity is presented.
• Scientific advances about yeast cell responses to MOx NPs are updated and discussed.
... According to previous studies, NiO-NPs induced cellular death in different human cell lines such as neuron, liver, lung, airway epithelial, and breast cells and rat kidney epithelial cells. 4,7,[23][24][25][26][27] Our results could indicate that the Caco-2 cell line was more vulnerable than other previously studied cell lines to NiO-NP-induced cytotoxic effects. ...
... Previously, changes in mRNA levels in the genes related to the apoptosis pathway were reported. 27,29,34 Duan et al. 35 studied the role of apoptosis in NiO-NP-induced toxicity in human bronchial epithelial cells (BEAS-2B) by investigating the impacts of NiO-NPs on sirtuin 1, a NAD-dependent deacetylase. NiO-NPs (5-20 µg/cm 2 ) caused cytotoxicity by an apoptotic process, and showed a suppression effect on sirtuin 1, which could underlie the NiO-NP-induced apoptosis via tumor protein p53 and bcl-2-associated X protein. ...
Objectives:
The superior properties of nickel oxide-nanoparticles (NiO-NPs) have led to their wide use in various fields. However, there is little comprehensive knowledge about their toxicity, especially after oral exposure. The toxic effect of NiO-NPs of mean size 15.0 nm was investigated in Caco-2 (human intestinal epithelial) cells as no study has been performed on their intestinal toxicity.
Materials and methods:
Following identification of their particle size distribution and cellular uptake potential, the risk of exposure to NiO-NPs was evaluated by cellular morphologic changes, cyto- and genotoxic potentials, oxidative damage, and apoptotic induction.
Results:
NiO-NPs induced a 50% reduction in cell viability at 351.6 μg/mL and caused DNA damage and oxidative damage at 30-150 μg/mL. It appears that apoptosis might be a main cell death mechanism in NiO-NP-exposed intestinal cells.
Conclusion:
NiO-NPs might be hazardous to the gastrointestinal system. The results should raise concerns about using NiO-NPs in food-contact appliances and about NiO-NP-containing wastes. Further in vivo and in vitro research should be conducted to explain the specific toxicity mechanism of these particles and reduce their risk to humans.
... [87] In Raw 264.7 cells, exposure to subtoxic concentrations of NiO NPs decreased cell viability and the production of ROS [88•]. Another study demonstrated the toxic effects on HEp-2 and MCF-7 cells exposed to NiO NPs [89]. NiO NPs induced cell death and cell proliferation in A549 and HepG2 cells [90]. ...
Purpose of Review
Nickel oxide nanoparticles (NiO NPs) have attracted considerable interest in multiple industries because of their distinct properties and wide range of potential applications. However, concerns regarding their potential adverse health effects have prompted extensive research efforts to understand their toxicity and develop appropriate safety guidelines.
Recent Findings
Recent studies have demonstrated that exposure to NiO NPs can induce harm in a variety of animal models, plants, ecological systems, and in vitro cell models. Research on the mechanism of signaling pathways implicated in respiratory system toxicity and hepatotoxicity has shown that NiO NPs can lead to organ damage by triggering downstream signaling through the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK)/Smad, phosphoinositide 3-kinase (PI3K/AKT), and hedgehog signaling pathways. High-throughput RNA sequencing has been used in toxicity studies to detect important changes in the transcriptome at the mRNA and pathway levels. Additionally, NiO NPs have been found to cause NiO NPs induce neurotoxicity, genotoxicity, and ecotoxicity in plants and earthworms, potentially through mechanisms involving oxidative stress and inflammatory factors.
Summary
This review provides a comprehensive summary of current research progress on the health effects of NiO NPs, focusing on their application, routes of exposure, and potential toxicity mechanisms. The study also evaluates evidence on the impact of NiO NPs on organ systems, including the respiratory, liver, nervous, genotoxic, reproductive and developmental effects. Lastly, the review suggests further research directions to improve understanding of the toxic effects and mechanisms of NiO NPs for safer application.
... In our recent study, the cytotoxicity effect of SnO 2 / calcite against HepG2 cells was explored [29]. A significant reduction of cell viability in up to 40% of HEp-2 and MCF-7 cancer cells exposed to NiO nanoparticles was reported [30]. In our study, cellulose-clay-NiO nanocomposite was used as an anticancer agent against cervical cancer cells using viability assay. ...
Cervical cancer is known as the fourth most common case among women worldwide. Despite several treatments, still cervical cancer is a significant cause of health problems in women. Nowadays, nanotechnology has been used to increase cancer treatment efficacy. So, the study aims to synthesize the natural nanocomposite and evaluate its anticancer activity, cell membrane fluidity, and morphology changes against HeLa cancer cells. Cellulose was extracted from bare wastes. NiO nanoparticles and clay were added to it to have cellulose-clay-NiO nanocomposite. This novel nanocomposite was characterized using Fourier transform infrared, scanning electron microscopy, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDAX), X-ray diffraction (XRD), and elemental analysis. TEM images show a spherical shape with an average size of 19 nm. EDAX and elemental analysis show C, O (cellulose), Si, Al (SiO2 and Al2O3 of clay), and Ni (NiO) confirming the successful synthesis of the nanocomposite. XRD pattern of nanocomposite shows the presence of cellulose, NiO, and clay. Cell viability, reactive oxygen species (ROS), membrane fluidity and apoptosis assay were estimated upon treatment with nanocomposite on HeLa cancer cell lines. The MTT assay of nanocomposite displayed concentration-dependent cytotoxicity. The half-maximal inhibitory concentration was found to be 106.9 µg/mL. The enhanced level of ROS in the treated cells caused a decline in cell membrane fluidity and finally induced apoptosis in HeLa cells. So, exposure to nanocomposite resulted in decreased cell viability and excitation of apoptosis. Therefore, it can be used as a biodegradable, cost-effective drug for cancer treatment.
... Nickel compounds can cause histone hyperphosphorylation, hypermethylation, and hyperubiquitination [180][181][182]. In vitro studies demonstrated Ni sulphate's ability to cause apoptosis in human hepatoma cells, human T hybridoma cells, and human breast cancer [183][184][185]. It also affects intestinal microbiota and increases the chances of gastric diseases [186]. ...
Introduction: Drinking water contaminated with heavy metals like arsenic, cadmium, nickel, mercury, chromium, zinc, lead, etc. is becoming a major health concern. Some trace elements have been linked to neurotoxic effects and an increased risk of neurodevelopmental disorders, although there is still an area for further investigations on how they may affect neurological and psychiatric illnesses. It is widely acknowledged that the generation of reactive oxygen species causes oxidative damage and other detrimental health effects, and is the main mechanism underlying heavy metal-induced toxicity in contaminated drinking water. The aim: The main objective of this narrative review was to summarize the current knowledge regarding the concentrations of chosen trace elements in drinking water and their possible relationship with neurological and psychiatric disorders. Material and method: The available literature was reviewed using PubMed, Scopus, and Web of Sciences platforms. The analysis included both reviews and original studies. Discussion: Some elements such as aluminum, arsenic, lithium, or nickel have been suggested to be risk factors for psychoneurological disorders. Further, studies suggest that some neurobehavioral disorders might be due to the collective action of metals in drinking water. Keywords: trace elements; drinking water; contamination; neurological disorder; psychiatric disorder
... Nickel compounds can cause histone hyperphosphorylation, hypermethylation, and hyperubiquitination [180][181][182]. In vitro studies demonstrated Ni sulphate's ability to cause apoptosis in human hepatoma cells, human T hybridoma cells, and human breast cancer [183][184][185]. It also affects intestinal microbiota and increases the chances of gastric diseases [186]. ...
Introduction: Drinking water contaminated with heavy metals like arsenic, cadmium, nickel, mercury, chromium, zinc, lead, etc. is becoming a major health concern. Some trace elements have been linked to neurotoxic effects and an increased risk of neurodevelopmental disorders, although there is still an area for further investigations on how they may affect neurological and psychiatric illnesses. It is widely acknowledged that the generation of reactive oxygen species causes oxidative damage and other detrimental health effects, and is the main mechanism underlying heavy metal-induced toxicity in contaminated drinking water. The aim: The main objective of this narrative review was to summarize the current knowledge regarding the concentrations of chosen trace elements in drinking water and their possible relationship with neurological and psychiatric disorders. Material and method: The available literature was reviewed using PubMed, Scopus, and Web of Sciences platforms. The analysis included both reviews and original studies. Discussion: Some elements such as aluminum, arsenic, lithium, or nickel have been suggested to be risk factors for psychoneurological disorders. Further, studies suggest that some neurobehavioral disorders might be due to the collective action of metals in drinking water. Keywords: trace elements; drinking water; contamination; neurological disorder; psychiatric disorder
... Same is true for nano NiO that are used in bulks as photo-catalyst, electrocatalyst, in energy devices and in gas sensors due to their semiconductor nature (Zaitseva et al., 2016;Cao et al., 2019). A couple of in vitro studies have already reported that NiO NPs are e toxic for mammalian cells (Siddiqui et al., 2012;Ahamed et al., 2013) but in vivo studies were lacking for NiO NPs. We hypothesized that people working in industries where NiO NPs are used as raw material and the end users of these products are seriously exposed to hazards of these O n l i n e F i r s t A r t i c l e materials. ...
early access) Authors' Contribution FI designed and supervised the project and revised the final manuscript. MNA and LN synthesized and characterized the Ni oxide nanoparticles. MFH, AA and MA maintained the mice colony and performed all mentioned experiments. All data were generated in-house and that no paper mill was used. Ni oxide nanoparticles (NiO NPs) are extensively used in industries dealing with welding, electroplating and in production of alloys but despite of their large scale uses, it is expected that they might have lot more drawbacks than their bulky counter parts. Present investigation was aimed to document the effect of two different doses of NiO NPs on behavior of albino mice in a sex specific manner. Five weeks old albino mice (N = 48) of both sex were intraperitoneally injected with either low dose (20 mg) or high dose (50mg/ ml saline/ Kg body weight) of NiO NPs (average particle size 43 nm) for 14 days. Control groups were treated with saline solution. A series of behavioral tests were conducted in all subjects. Both low and high dose of NiO NPs treated male mice, during rota rod test, spent significantly less time on rotating rod than controls. Male mice treated with both doses of NiO NPs performed more stretch attend reflex than control. Female mice injected with high dose of NiO NPs had significantly reduced mobile and immobile episodes during open field test than mice exposed to low dose and control group. High dose of NiO NPs treated females had reduced line crossing, stretch attend reflex, number of approaches to familiar and novel objects than low dose NiO NPs and saline treated female mice. No change in body weight was observed when this parameter was compared between NiO NPs and saline injected albino mice of both sexes. In conclusion, we are reporting that NiO NPs can affect the muscular activity, object recognition capacity and exploratory behaviour of albino mice. The effects were more pronounced at higher dose and in female mice.
... Same is true for nano NiO that are used in bulks as photo-catalyst, electrocatalyst, in energy devices and in gas sensors due to their semiconductor nature (Zaitseva et al., 2016;Cao et al., 2019). A couple of in vitro studies have already reported that NiO NPs are e toxic for mammalian cells (Siddiqui et al., 2012;Ahamed et al., 2013) but in vivo studies were lacking for NiO NPs. We hypothesized that people working in industries where NiO NPs are used as raw material and the end users of these products are seriously exposed to hazards of these O n l i n e F i r s t A r t i c l e materials. ...
... However, at high dosages (160 and 320 lg/ml) curcumin induces moderate toxicity to GC-1 spg cells. Cytocompatibility of curcumin in these concentrations was also observed by other investigators (Ahamed et al., 2022;Ghosh et al., 2020;Siddiqui et al., 2012). ...
Current research focuses on the effects of nanomaterials on the human reproductive system. Nanostructures can cross the epithelial and blood-testicular barriers and pose risks to the reproductive organs. Oxidative stress has been proposed as a possible mechanism of reproductive toxicity caused by nanomaterials. Dietary curcumin could be a therapeutic drug for nanomaterial-induced reproductive toxicity. Studies on effect of commonly used nickel (II) oxide nanoparticle (NiO NPs) on male reproductive organs and their attenuation by natural antioxidant curcumin is scarce. This work intended to study the attenuating potential of curcumin against NiO NPs-induced toxicity in mouse spermatogonia GC-1 spg cells. Plausible mechanisms of alleviating effect curcumin against NiO induced reproductive toxicity was explored through oxidative stress pathway. NiO NPs was synthesized via chemical co-precipitation route and characterized by SEM, TEM, and XRD. NiO NPs was found to induce dose-dependent cytotoxicity in GC-1 spg cells (10–320 µg/ml for 24 h) whereas curcumin did not exert any effect in concentration range of 1–80 µg/ml. Interestingly, cytotoxic response of NiO NPs in GC-1 spg cells was significantly attenuated by curcumin. The higher expression of caspase-3 gene and loss of mitochondrial membrane potential after treatment with NiO NPs were effectively alleviated by curcumin. The increase in intracellular pro-oxidant levels (hydrogen peroxide, malondialdehyde, and reactive oxygen species) after exposure to NiO NPs was also mitigated by curcumin. Moreover, glutathione depletion and lower activity of several antioxidant enzymes (GPx, SOD, and CAT) after NiO NPs were further almost reverted by curcumin. We believe, this is the first preliminary study showing that NiO NPs induced cytotoxicity in mouse spermatogonia cells was mitigated by curcumin via oxidative stress. The therapeutic effect of dietary antioxidant curcumin against nanomaterial-induced reproductive toxicity is warranted further research.
... Наблюдалась активация каспазы-3, фрагментация ДНК, экспрессия маркеров апоптоза. Действие НЧ на клетки могло быть блокировано добавлением куркумина [22]. В клетках легочного эпителия хомяка V79 при действии НЧ NiO размером 30 нм в концентрации 250 и 2500 мкг/мл наблюдали появление микроядер. ...
Nanoparticles of nickel (Ni) and its compounds attract a lot of attention bearing in mind their promising innovative properties allowing their use as catalysts, components in electrical appliances, electronic devices and photonic appliances, and materials used in producing medications, diagnostic preparations, and pesticides. Production volumes of these materials in their nano-form are likely to grow rapidly in the nearest future and it involves greater loads created by these nanomaterials on a human body. And we should remember that Ni and its compounds are highly toxic for humans even in their traditional disperse forms. Their toxicity induces oxidative stress, cellular membranes and mitochondria dysfunction, expression of nuclear transcription factors that are responsible for apoptosis, caspases, as well as proto-oncogenes. Leading role in toxicity of Ni-containing nanomaterials obviously belongs to ions of heavy Ni++ being emitted from them since this heavy metal has pro-oxidant properties and influences enzyme activity and gene expression. Cytotoxic effects produced by Ni-containing nanomaterials were revealed in Model experiments in vitro performed with suing cellular cultures that were morphologically and functionally similar to epithelial cells of respiratory and gastrointestinal tract, liver, kidneys, and nervous system; these materials were able to stimulate oxidant stress, influence expression of apoptosis proteins and nuclear transcription factors, induce apoptosis and necrosis. There are data indicating that Ni-containing nanomaterials can produce malignant transforming effects in vitro. All the above mentioned proves that nickel compounds in their nanoform are a new hazardous factor that requires assessing related risks for workers, consumer, and population in general. Our review focuses on analyzing literature sources on cytotoxicity of Ni-containing nanomaterials and their effects produced on molecular-genetic and cellular levels taken over a period starting from 2011.
... As we can see in Figure 4A, curcumin did not cause cytotoxicity to BeWo cells up to 100 µg/mL. Earlier studies have also observed the biocompatibility of curcumin in different types of mammalian cell lines such as human airway epithelial (HEp-2), human breast cancer (MCF-7), and embryonic rat heart-derived (H9c2) cells [44,45]. ...
The placenta is an important organ that maintains a healthy pregnancy by transporting nutrients to the fetus and removing waste from the fetus. It also acts as a barrier to protect the fetus from hazardous materials. Recent studies have indicated that nanoparticles (NPs) can cross the pla-cental barrier and pose a health risk to the developing fetus. The high production and widespread application of copper oxide (CuO) NPs may lead to higher exposure to humans, raising concerns of health hazards, especially in vulnerable life stages, e.g., pregnancy. Oxidative stress plays a crucial role in the pathogenesis of adverse pregnancy outcomes. Due to its strong antioxidant activity, dietary curcumin can act as a therapeutic agent for adverse pregnancy. There is limited knowledge on the hazardous effects of CuO NPs during pregnancy and their mitigation by curcumin. This study aimed to investigate the preventive effect of curcumin against CuO NP-induced toxicity in human placental (BeWo) cells. CuO NPs were synthesized by a facile hydrothermal process and characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and photoluminescence techniques. We observed that curcumin did not induce toxicity in BeWo cells (1-100 µg/mL for 24 h), whereas CuO NPs decreased the cell viability dose-dependently (5-200 µg/mL for 24 h). Interestingly, CuO NP-induced cytotoxicity was effectively mitigated by curcumin co-exposure. The apoptosis data also exhibited that CuO NPs modulate the expression of several genes (p53, bax, bcl-2, casp3, and casp9), the activity of enzymes (caspase-3 and-9), and mitochon-drial membrane potential loss, which was successfully reverted by co-treatment with curcumin. The mechanistic study suggested that CuO-induced reactive oxygen species generation, lipid peroxida-tion, and higher levels of hydrogen peroxide were significantly alleviated by curcumin co-exposure. Moreover, glutathione depletion and the lower activity of antioxidant enzymes (superoxide dis-mutase, glutathione peroxidase, and catalase) were effectively mitigated by curcumin. We believe this is the first report exhibiting that CuO-induced toxicity in BeWo cells can be effectively alleviated by curcumin. The pharmacological potential of dietary curcumin in NP-induced toxicity during pregnancy warrants further investigation.
... 39 Also, in cultured human cells, nickel oxide NPs cause cytotoxicity, oxidative stress, and apoptosis, which is inhibited by the dietary antioxidant curcumin. 40 Our findings indicate that the oral intake of AL 2 O 3 -NP decreases bw and increases oxidative stress and toxicity, leading to apoptosis in the livers of mice, by the following mechanisms: (A) the regulation of P53 appears to be dependent on NRf2 and the level of Hsp70. (B) An increase in NRf2 is considered to be a non-defense system against oxidative stress, decreasing the endogenous antioxidant defense system and accelerating the increase in cytochrome C-induced apoptosis. ...
The potential influence of nanoparticles (NPs) on the liver and bone marrow has received attention. The aim of this work was to evaluate the effect of nanocurcumin on the oxidative stress, apoptosis, and toxicity induced by Al2O3 and its NPs. The experimental animals (n = 72 mice) were divided into the following groups: group I, as a control; groups II and III, as aluminum oxide and its NPs (6 mg/kg); group IV, as aluminum oxide + nanocurcumin (Al2O3 + N-Cur, 20 mg/kg); and group V, as aluminum oxide NPs + nanocurcumin (Al2O3-NP + N.Cur., 20 mg/kg). Al2O3 and its NP groups significantly increased p53, Nrf2 levels, and the white blood cell count. They also decreased the Hsp70 level, antitrypsin, immunoglobulin G, and the red blood cell count. In addition, they significantly decreased the total and differential bone marrow cell counts and the maturation index ratio (MIR). Nanocurcumin (N.Cur.) reverted the previous proteins, blood parameters, total bone marrow cell count, and the MIR as M/E, I/Mg, MMI, I/Me, and EMI to normal. Furthermore, N.Cur. prevented apoptosis and reduced the histopathological score and collagen fiber percentage caused by Al2O3 and its NPs in the liver. Nanotechnology was used to increase the therapeutic efficiency of curcumin against the harmful effects of oxidative stress associated with Al2O3 NPs.
... glutathione peroxidase, catalase, and superoxide dismutase and induce cytotoxicity in cultured human cells. Abrogation of cytotoxicity by an established antioxidant, curcumin, further supports this conclusion (Siddiqui et al., 2012). Complexes formed between NPs and enzyme proteins are known to affect the skeleton and secondary structure of these enzymes (Zhao et al., 2019). ...
Increased application of engineered nanoparticles in different sectors viz. agriculture, commerce, industry, and medicine has raised serious public health issues. Nanoparticles of nickel have been increasingly used as catalysts, conductive pastes, adhesives, nanowires, and nanofilters. Human and animal exposure to these particles may cause toxicity in different organs/systems. Studies made in the past had demonstrated their toxicity in liver, kidney, and lungs. However, their reproductive effects remain poorly understood. Therefore, the present study on reproductive toxicity of nickel nanoparticles (<30 nm) was executed in female Wistar rats. A comparison of results obtained in nickel microparticle-treated rats was also made. Rats were administered nano and microparticles through gavage at a dosage of 5 mg/kg body weight each for two exposure periods; that is, 15 and 30 days. Ovaries removed from these rats were analyzed to study the effects of nickel bioaccumulation on synthesis of steroid hormones, lipid peroxidation, apoptosis, and oxidative stress. Structural changes were monitored through histopathological and ultrastructural observations. The present study showed exposure time-dependent differences in the toxicity of nickel nano and microparticles in the ovary of rats. Nano nickel was cumulative in the ovaries. It affected steroidogenesis. Further, increased generation of reactive oxygen species and enhanced oxidative stress may have contributed to cytotoxicity. It was concluded that exposure to nano nickel might induce irreversible damage in the ovaries of rat.
... [43][44][45] The contribution of ROS in NiONP induced renal cell injury has also been reported earlier by a few investigations. [24,46] In general NPs can generate ROS through multiple mechanisms. These include creation of acidic environment in the cell , [47] interaction with microsomes and mitochondria, [48] interaction with redox active proteins [49] and activation of intracellular signaling pathways. ...
A comparative and time dependent study on the effects of nickel oxide nano and nickel oxide microparticles (5 mg/kg body weight) each, has been performed in the kidney of male Wistar rats at two intervals of 15 and 30 days. Morphological, functional changes and effects on antioxidant enzymes in the kidney were studied. Exposure to both, NiONPs and NiOMPs significantly enhanced the generation of reactive oxygen species viz. malondialdehyde, hydrogen peroxide and nitric oxide in rat kidney. However, increase was higher in NiONPs treated rats than NiOMPs treated rats. Diminished values for reduced glutathione and enzymes, that is, superoxide dismutase, glutathione peroxidise and catalase confirmed the role of oxidative stress in NiONPs induced nephrotoxicity. Increased oxidative DNA damage and histopathological changes further supported this hypothesis. Present results suggest that nanoparticles of nickel are more toxic to kidney than nickel metal ions. Reactive oxygen species are a critical factor in NiONPs induced renal toxicity in rat.
... Same is true for nano NiO that are used in bulks as photo-catalyst, electrocatalyst, in energy devices and in gas sensors due to their semiconductor nature (Zaitseva et al., 2016;Cao et al., 2019). A couple of in vitro studies have already reported that NiO NPs are e toxic for mammalian cells (Siddiqui et al., 2012;Ahamed et al., 2013) but in vivo studies were lacking for NiO NPs. We hypothesized that people working in industries where NiO NPs are used as raw material and the end users of these products are seriously exposed to hazards of these materials. ...
... Curcumin (Figure 2), the main phenolic compound in spice turmeric, is reported as a natural antioxidant supplement against NiO-NPs, TiO 2 -NPs, and ZnO-NPs. Siddiqui et al. [130] reported that curcumin reduces ROS and lipid peroxidation levels, as well as increases the GSH level in NiO-NP-induced toxicity in human airway epithelial (HEp-2) and breast cancer (MCF-7) cells. Another in vitro study showed antioxidant protective effects of curcumin on DNA damage induced by TiO 2 -NPs in lymphocytes [132]. ...
Nanoparticles (NPs) are used in many products and materials for humans such as electronics, in medicine for drug delivery, as biosensors, in biotechnology, and in agriculture, as ingredients in cosmetics and food supplements. Besides that, NPs may display potentially hazardous properties on human health and the environment as a consequence of their abundant use in life nowadays. Hence, there is increased interest of researchers to provide possible therapeutic agents or dietary supplements for the amelioration of NP-induced toxicity. This review summarizes the new findings in the research of the use of antioxidants as supplements for the prevention and alleviation of harmful effects caused by exposure of organisms to NPs. Also, mechanisms involved in the formation of NP-induced oxidative stress and protective mechanisms using different antioxidant substances have also been elaborated. This review also highlights the potential of naturally occurring antioxidants for the enhancement of the antioxidant defense systems in the prevention and mitigation of organism damage caused by NP-induced oxidative stress. Based on the presented results of the most recent studies, it may be concluded that the role of antioxidants in the prevention and treatment of nanoparticle-induced toxicity is unimpeachable. This is particularly important in terms of oxidative stress suppression.
... There was caspases-3 activation, DNA fragmentation, and apoptosis markers expression. Effects produced by NPs on cells could be blocked by adding curcumin [22]. Micronucleuses appeared in lung epithelial cells of V79 hamster under exposure to NiO NPs sized 30 nm in concentrations equal to 250 and 2,500 µg/ml. ...
Nanoparticles of nickel (Ni) and its compounds attract a lot of attention bearing in mind their promising innovative properties allowing their use as catalysts, components in electrical appliances, electronic devices and photonic appliances, and materials used in producing medications, diagnostic preparations, and pesticides. Production volumes of these materials in their nano-form are likely to grow rapidly in the nearest future and it involves greater loads created by these nanomaterials on a human body. And we should remember that Ni and its compounds are highly toxic for humans even in their traditional disperse forms. Their toxicity induces oxidative stress, cellular membranes and mitochondria dysfunction, expression of nuclear transcription factors that are responsible for apoptosis, caspases, as well as proto-oncogenes. Leading role in toxicity of Ni-containing nanomaterials obviously belongs to ions of heavy Ni++ being emitted from them since this heavy metal has pro-oxidant properties and influences enzyme activity and gene expression. Cytotoxic effects produced by Ni-containing nanomaterials were revealed in Model experiments in vitro performed with suing cellular cultures that were morphologically and functionally similar to epithelial cells of respiratory and gastrointestinal tract, liver, kidneys, and nervous system; these materials were able to stimulate oxidant stress, influence expression of apoptosis proteins and nuclear transcription factors, induce apoptosis and necrosis. There are data indicating that Ni-containing nanomaterials can produce malignant transforming effects in vitro. All the above mentioned proves that nickel compounds in their nanoform are a new hazardous factor that requires assessing related risks for workers, consumer, and population in general. Our review focuses on analyzing literature sources on cytotoxicity of Ni-containing nanomaterials and their effects produced on molecular-genetic and cellular levels taken over a period starting from 2011.
... Arrow: degeneration in the epidermis oxidative stress in the body, and eventually activate the mitochondrial pathway of apoptosis [60,61]. Previous studies have reported that nickel nanoparticles induce intracellular ROS production in a dose-dependent manner [56,62,63]. In the highest nanoparticle exposure groups (2000 mg/L), the increase in ROS level at the end of the experiment was determined to be higher in PdCu/MWCNT NPs (527.65 fluorescence intensity/mg protein) than in PdNi/MWCNT NPs (460.10 fluorescence intensity/mg protein) (Fig. 10). ...
Bimetallic nanoparticles are synthesized using two different metal elements and used recently in many fields. However, limited studies related to the ecotoxic effects of nanoparticles available in the literature. The purpose of this study is to synthesize and characterize bimetallic PdCu/MWCNT and PdNi/MWCNT NPs and investigate their ecotoxic effects on earthworms. For this purpose, we injected approximately 20 µL of various concentrations of bimetallic PdCu/MWCNT and PdNi/MWCNT NPs (1, 10, 100, 1000, and 2000 mg/L) into the coelomic space of earthworms. We evaluated survival rate, malformations, reactive oxygen species (ROS) level, 8-OHdG content, and histopathological changes in earthworms at the 48th hour after exposure. PdCu/MWCNT and PdNi/MWCNT NPs were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) pattern, and Raman-scattering spectroscopy. Toxicological examinations showed that PdCu/MWCNT NPs reduced the survival rate of earthworms (2000 mg/L, 84%) and caused various malformations (various lesions, thinning, swelling, and rupture), but nonsignificant effects of survival rate and malformations were observed in earthworms using PdNi/MWCNT NPs. The histopathological examinations of earthworm tissues exposed with PdNi/MWCNT determined that tissues in all treatment groups had a normal histological appearance. However, at a concentration of 2000 mg/L of PdCu/MWCNT NPs, atrophy in the longitudinal muscle layer and less degenerative cells in the epidermis layer were observed in earthworm tissues. It was determined that PdNi/MWCNT and PdCu/MWCNT NPs caused significant increases in ROS levels and 8-OHdG activity in earthworm tissues after 48 h. Finally, our results demonstrated that the toxicity of PdNi/MWCNT NPs was detected to be lower than PdCu/MWCNT NPs. However, both nanoparticles may pose a toxicological risk at high concentrations (1000 and 2000 mg/L). These findings will provide valuable information to studies on the use of PdNi/MWCNT NPs in wastewater treatment systems, industrial and medical fields, which have been determined to have less ecotoxicological risk.
... Another study investigated that nickel oxide (NiO) induced cytotoxicity and apoptosis in cultured human airway epithelial (HEp-2) and human breast cancer (MCF-7) cells. NiO was also found to induce oxidative stress in dose-dependent manner indicated by glutathione depletion, ROS induction, and lipid peroxidation [24]. These metallic ions induce innate immune system activation, primarily via monocyte or macrophage activation [25]. ...
Orthopedic devices are used in pathologic disorder as an adjunct to bone grafts to provide immediate structural stability. Unfortunately, the use of metallic devices has some complications. This study aimed to characterize the oxidative stress biomarker and the anti-oxidant enzyme profiles during bone regeneration. New Zealand White rabbits were divided into 4 groups: Group (
... The intratracheal instillation of Ni-NPs (0.2 mg) in rats also increased the levels of interleukin (IL)-1, monocyte chemotactic protein-1, and IL-1 in BALF of lung tissues (Morimoto et al., 2010). Ni-NPs treatments in human breast carcinoma (MCF-7) and human airway epithelial cell line induced oxidative stress markers that triggered caspase-3 activity and depleted GSH level in dose-response relation (Ahamed and Alhadlaq, 2014; Siddiqui et al., 2012). The cell viability assay showed increased viability (> 80%) in human fibroblasts at 0.22 mg and 2.25 mg when incubated for 24 h. ...
Nickel nanoparticles (Ni-NPs) are widely used for multiple purposes in industries. Ni-NPs exposure is det-
rimental to ecosystems owing to widespread use, and so their toxicity is important to consider for real-world
applications. This review mainly focuses on the significant pathophysiological activities of Ni-NPs in various
research models. Ni-NPs are stated to be more toxic than bulk forms because of their larger surface area to
volume ratio and are reported to provoke toxicity through reactive oxygen species generation, which leads
to the upregulation of nuclear factor--
B and promotes further signaling cascades. Ni-NPs may contribute to
provoking oxidative stress and apoptosis. Hypoxia-inducible factor 1� and mitogen-activated protein kinases
pathways are involved in Ni-NPs associated toxicity. Ni-NPs trigger the transcription factors p-p38, p-JNK,
p-ERK1/2, interleukin (IL)-3, TNF-�, IL-13, Fas, Cyt c, Bax, Bid protein, caspase-3, caspase-8, and caspase-9.
Moreover, Ni-NPs have an occupational vulnerability and were reported to induce lung-related disorders
owing to inhalation. Ni-NPs may cause serious effects on reproduction as Ni-NPs induced deleterious effects
on reproductive cells (sperm and eggs) in animal models and provoked hormonal alteration. However, recent
studies have provided limited knowledge regarding the important checkpoints of signaling pathways and less focused on the toxic limitation of Ni-NPs in humans, which therefore needs to be further investigated.
... Furthermore, the extensive use of synthesized nanoparticles warrants a safety evaluation by toxicologists. Different studies conducting in vitro tests of NiO NPs on mammalian cells documented a toxicological response (Horie et al. 2009(Horie et al. , 2011Siddiqui et al. 2012;Ahamed et al. 2013). When the nanoparticles are ingested, they are distributed to various regions because of their small size. ...
The green synthesized nanoparticles have been determined as a novel pesticide against arthropod pests. This study was designed to evaluate the in vitro acaricidal activity of green synthesized nickel oxide nanoparticles (NiO NPs) using aqueous extract of Melia azedarach ripened fruits against different developmental stages of the camel tick Hyalomma dromedarii in addition to their toxic effect on laboratory animals. The synthesized NiO NPs were characterized by UV–visible (UV–Vis) spectroscopy, Fourier transforms infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). The UV–Vis spectra of the NiO NPs showed an absorption peak at 307 nm. FTIR analysis showed the possible functional groups used for capping and stabilization of NiO NPs with strong bands at 3416.2 and 1626.6 cm−1. The SEM images of the NiO NPs exhibited a size ranging from 21 to 35 nm. The immersion test was used for the in vitro application of the synthesized NiO NPs on the various tick stages (egg, nymph, larva, and adult). Mortality percentages and LC50 values of each tick stage were calculated. The oviposition and hatchability of the engorged females were monitored for the survived tick after treatment. The LC50 values for NiO NPs on embryonated eggs, larvae, and engorged nymphs were 5.00, 7.15, and 1.90 mg/mL, respectively. The egg productive index (EPI), egg number, and hatchability (%) were lower in females treated with the NiO NPs than in control ticks. The toxicity of the NiO NPs on laboratory animals was also investigated using Swiss albino mice by oral dose of 500 mg/kg/day administration for five consecutive days. The hematological, biochemical, and histopathological changes were evaluated. The hematological analysis showed significant increase in the level of white blood cells (WBC) and hemoglobin (Hb). Biochemical analysis showed non-significant decrease in alkaline phosphatase (ALP) and alanine amino transferase (ALT). We concluded that NiO NPs have a significant acaricidal activity as demonstrated on eggs, larvae, engorged nymphs, and fully fed females of H. dromedarii. From a toxicological point of view further in vivo investigations are needed to determine the mechanism of toxic effect of NiO NPs.
... Previous in vitro studies have demonstrated that Ni compounds trigger the apoptotic process through caspase-3 activation in cultured cells. The release of caspase-3 is triggered by cytochrome c release from the mitochondria (Ahamed et al., 2011;Siddiqui et al., 2012). Also, increase in pro-apoptotic protein Bax, and a simultaneous decrease in anti-apoptotic protein Bcl-2 was shown to have triggered the intrinsic apoptotic mechanisms following Ni treatment (Guo et al., 2016;Huang et al., 2013) (Fig. 4). ...
Nickel (Ni) is a ubiquitous metal with extensive industrial and nonindustrial applications. The increasing application of Ni has made it an unavoidable environmental pollutant; hence an increase in human overexposure and accumulation. Over-exposure to Ni results in hematotoxicity, immunotoxicity, genotoxicity, hepatotoxic, carcinogenicity and more notably, neurotoxicity. The neurological impact of Ni has garnered global concern and has made it subject to numerous investigations and published reports. Thus, this chapter discusses the neurologic impact of Ni overexposure such as behavioral, neurochemical and structural alterations, as well as addresses potential mechanism of Ni neurotoxicity. Additionally, the chapter highlights several potential therapeutic neuroprotective agents able to mitigate Ni-induced neurotoxicity.
... They also have been extensively applied in battery electrodes, sensor magnetic materials, diesel-fuel, additives, and catalyzers, which has increased the probability of human exposure (Magaye et al. 2016). NiONPs can suppress the viability of human breast cancer (Siddiqui et al. 2012). Unfortunately, severe injuries in the lung and liver of rats following exposure to NiONPs were documented (Horie et al. 2011;Liu et al. 2017). ...
Nickel oxide nanoparticles (NiONPs) are involved in several applications but still have some adverse effects. Apigenin (APG) is a widespread natural product with antioxidative, anticancer, and anti-inflammatory properties. The present work aimed to study the protective role of APG against the NiONP-induced toxicity in male Wistar rats. Rats were randomly distributed to one control group and three treated groups. The treated groups were orally administered NiONPs (100 mg/kg) alone, APG (25 mg/kg) alone, or APG 1 h before NiONPs, once daily for 28 days. Blood, liver, and kidney were collected after 7, 14, and 28 days of administration for Ni accumulation, hematological, biochemical, histological, and transmission electron microscopy (TEM) investigations. As compared to the controls, the administration of NiONPs alone significantly elevated the levels of Ni, malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, creatinine, urea, blood urea nitrogen, and the activity of alanine and aspartate aminotransferases as well as the count of white blood cells. Besides, marked reductions in the activity of superoxide dismutase, and the levels of glutathione, high-density lipoprotein cholesterol, total proteins, albumin, globulin, hemoglobin, packed cell volume, and red blood cell count were reported. Histologically, the liver and kidney of rats administered NiONPs alone showed remarkable disturbances. According to TEM, subcellular alterations were observed in the liver and kidney of rats administered NiONPs alone. In contrast, APG administering before NiONPs substantially alleviated all the studied parameters. In conclusion, APG can ameliorate the NiONP-induced hepatotoxicity and nephrotoxicity in male Wistar rats.
... This may result in ROS production and subsequently in oxidative stress . Wise Sr et al. (2010) and Siddiqui et al. (2012) reported that oxidative stress is the important mechanism of NP toxicity. The level of antioxidant defense mechanism was found to be changed when oxidative stress is induced (Nel et al. 2006;AshaRani et al. 2008). ...
In the course of time, there has been an increased usage of commercial products containing nanoparticles formulated from tin oxide (TNPs), cerium oxide (CNPs), aluminum oxide (ANPs), and zinc oxide (ZNPs). Despite the wide use of metal oxide nanoparticles (MONPs), understanding about their toxicity and mechanism of action are still unclear. In the present study, TNPs, CNPs, ANPs, and ZNPs were produced by the method of chemical synthesis and characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. The effect of these MONPs on human red blood cells (RBCs) and human skin cells (HaCaT) was investigated. In skin cells, these MONPs showed concentration-dependent cytotoxicity. ZNPs downregulated the glutathione and upregulated lipid peroxidation and lactate dehydrogenase activity which correlates with the increased reactive oxygen production in cells. Genotoxic effect of ZNPs was measured by comet tail assay that showed increased DNA damage in skin cells. Upregulation of Hsp70, Grp 78, and CYP1A1 was observed following ZNPs and ANPs treatment with skin cells. In the case of CNPs and TNPs, the changes were not significant. This study demonstrates the toxic effects of ZNPs and ANPs on skin cells, suggesting caution must be exercised in their use which may be restricted in the cosmetics industry and also products related to human use.
... NiO NPs are supposed to damage cells by generating oxidative stress (Ahmad et al. 2015). They are known to induce DNA damage (Abudayyak et al. 2017), inflammation, cell degeneration (Razavipour et al. 2015), cell cycle arrest (Ahmad et al. 2015) and cytogenetic alterations (Siddiqui et al. 2012, Saquib et al. 2017. ...
Introduction
This study was designed to report the biological effect of nickel oxide nanoparticles (NiO NPs) in albino mice.
Material and methods
Five weeks old albino mice of both sex were intraperitoneally injected either with 20 mg (low dose) or 50 mg/mL saline/kg body weight (high dose) of NiO NPs for 14 days. Saline-treated controls were maintained in parallel. Complete blood count, selected serum biochemical parameters and oxidative stress biomarkers from vital organs were determined in all subjects.
Results
Male mice treated with NiO NPS had increased blood urea nitrogen, elevated superoxide dismutase (SOD) in liver elevated MDA in liver, kidney and heart and reduced catalase activity in heart and kidney. Female mice treated with NiO NPs had significantly reduced serum albumin and total proteins, SOD in lungs and elevated MDA in liver.
Discussion
We are reporting that intraperitoneal injections of NiO NPs for 14 days drastically affect blood serum parameters and oxidative stress biomarkers from vital organs of albino mice.
Conclusion
Toxic effects of NiO NPs were dose and sex dependent and they were more pronounced at higher dose and in male mice.
With the exponential growth of the nanotechnology field, the global nanotechnology market is on an upward track with fast-growing jobs. Nickel (Ni)-containing nanoparticles (NPs), an important class of transition metal...
The use of nanotechnology in medical applications is increasing day by day. Thanks to their unique physical, chemical, mechanical, electronic, and magnetic properties, nanoparticles are successfully used in the diagnosis, treatment, and prevention of many diseases. Today, metallic nanoparticles constitute one of the most important instruments of nanotechnological approaches. It has been proven by previous studies that metallic nanoparticles show extremely strong antibacterial, antiviral, and anticancer activity. It is known that the presence of microorganisms and cancer cells that are resistant to current conventional drug applications is one of the biggest obstacles in preventing the spread of diseases in large geographies and their development in the human body. For this reason, there is a great need to develop new-generation treatment applications. The fact that metallic nanoparticles are effective on drug-resistant microorganisms and show a much higher inhibitory activity than current treatment applications has increased the importance of these agents in the field of medicine. However, the biggest obstacle to the application of metallic nanoparticles on living things is the toxicity of these agents. Today, various methods are being developed to reduce the toxicity of metallic nanoparticles and to apply them to humans. The biological production of nanoparticles by green synthesis method instead of chemical synthesis is the most important of these advanced methods. Within the scope of this review, different production methods of nickel oxide (NiO) nanoparticles, the importance of which has been increasing in recent years, and the factors that change the efficiency of the produced nanoparticles in biological applications are discussed, and recent studies on antimicrobial applications of NiO nanoparticles have been brought together.
Confronting the profound public health concern of alcohol-induced liver damage calls for inventive therapeutic measures. The social, economic, and clinical ramifications are extensive and demand a comprehensive understanding. This thorough examination uncovers the complex relationship between alcohol intake and liver damage, with a special emphasis on the pivotal roles of the Toll-like receptor 4 (TLR4)/NF-κB p65 and CYP2E1/ROS/Nrf2 signalling networks. Different alcohol consumption patterns, determined by a myriad of factors, have significant implications for liver health, leading to a spectrum of adverse effects. The TLR4/NF-κB p65 pathway, a principal regulator of inflammation and immune responses, significantly contributes to various disease states when its balance is disrupted. Notably, the TLR4/MD-2-TNF-α pathway has been linked to non-alcohol related liver disease, while NF-κB activation is associated with alcohol-induced liver disease (ALD). The p65 subunit of NF-κB, primarily responsible for the release of inflammatory cytokines, hastens the progression of ALD. Breakthrough insights suggest that curcumin, a robust antioxidant and anti-inflammatory compound sourced from turmeric, effectively disrupts the TLR4/NF-κB p65 pathway. This heralds a new approach to managing alcohol-induced liver damage. Initial clinical trials support curcumin's therapeutic potential, highlighting its ability to substantially reduce liver enzyme levels. The narrative surrounding alcohol-related liver injury is gradually becoming more intricate, intertwining complex signalling networks such as TLR4/NF-κB p65 and CYP2E1/ROS/Nrf2. The protective role of curcumin against alcohol-related liver damage marks the dawn of new treatment possibilities. However, the full realisation of this promising therapeutic potential necessitates rigorous future research to definitively understand these complex mechanisms and establish curcumin's effectiveness and safety in managing alcohol-related liver disorders.
The advancement in drug delivery systems in recent times has significantly enhanced therapeutic effects by enabling site-specific targeting through nanocarriers. These nanocarriers serve as invaluable tools for pharmacotherapeutic advancements against various disorders that enhance the effectiveness of encapsulated drugs by reducing their toxicity and increasing the efficacy of less potent drugs, thereby improving the therapeutic index. Inflammasomes, protein complexes located in the activated immune cell cytoplasm, regulate the activation of caspases involved in inflammation. However, aberrant activation of inflammasomes can result in uncontrolled tissue responses, contributing to the development of various diseases. Therefore, achieving a precise balance between inflammasome inhibition and activation is crucial for effectively treating inflammatory disorders through targeted functionalized nanocarriers. Despite the wealth of available data on the relevance of functionalized nanocarriers in inflammatory disorders, the nanotechnological potential to modulate inflammasomes has not been adequately explored. In this comprehensive review, we highlight the latest research on the modulation of the inflammasome cascade, both upregulating and downregulating its function, using nanocarriers in the context of inflammatory disorders. The utilization of nanocarriers as a therapeutic strategy holds immense potential for researchers aiming to effectively target and modulate inflammasomes in the treatment of inflammatory disorders, thus improving disease severity outcomes.
Nanotechnology has emerged in different fields of biomedical application, including lifestyle diseases like diabetes, hypertension, and chronic kidney disease, neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease, and different types of cancers. Metal nanoparticles are one of the most used drug delivery systems due to the benefits of their enhanced physicochemical properties as compared to bulk metals. Neurodegenerative diseases are the second most cause affecting mortality worldwide after cancer. Hence, they require the most specific and targeted drug delivery systems for maximum therapeutic benefits. Metal nanoparticles are the preferred drug delivery system, possessing greater blood-brain barrier permeability, biocompatibility, and enhanced bioavailability. But some metal nanoparticles exhibit neurotoxic activity owing to their shape, size, surface charge, or surface modification. This review article has discussed the pathophysiology of AD. The neuroprotective mechanism of gold, silver, selenium, ruthenium, cerium oxide, zinc oxide, and iron oxide nanoparticles are discussed. Again, the neurotoxic mechanisms of gold, iron oxide, titanium dioxide, and cobalt oxide are also included. The neuroprotective and neurotoxic effects of nanoparticles targeted for treating AD are discussed elaborately. The review also focusses on the biocompatibility of metal nanoparticles for targeting the brain in treating AD. The clinical trials and the requirement to develop new drug delivery systems are critically analyzed. This review can show a path for the researchers involved in the brain-targeted drug delivery for AD.
Use of nanoparticles have established benefits in a wide range of applications, however, the effects of exposure to nanoparticles on health and the environmental risks associated with the production and use of nanoparticles are less well-established. The present study addresses this gap in knowledge by examining, through a scoping review of the current literature, the effects of nanoparticles on human health and the environment. We searched relevant databases including Medline, Web of Science, ScienceDirect, Scopus, CINAHL, Embase, and SAGE journals, as well as Google, Google Scholar, and grey literature from June 2021 to July 2021. After removing duplicate articles, the title and abstracts of 1495 articles were first screened followed by the full-texts of 249 studies, and this resulted in the inclusion of 117 studies in the presented review.
In this contribution we conclude that while nanoparticles offer distinct benefits in a range of applications, they pose significant threats to humans and the environment. Using several biological models and biomarkers, the included studies revealed the toxic effects of nanoparticles (mainly zinc oxide, silicon dioxide, titanium dioxide, silver, and carbon nanotubes) to include cell death, production of oxidative stress, DNA damage, apoptosis, and induction of inflammatory responses. Most of the included studies (65.81%) investigated inorganic-based nanoparticles. In terms of biomarkers, most studies (76.9%) used immortalised cell lines, whiles 18.8% used primary cells as the biomarker for assessing human health effect of nanoparticles. Biomarkers that were used for assessing environmental impact of nanoparticles included soil samples and soybean seeds, zebrafish larvae, fish, and Daphnia magna neonates.
From the studies included in this work the United States recorded the highest number of publications (n = 30, 25.64%), followed by China, India, and Saudi Arabia recording the same number of publications (n = 8 each), with 95.75% of the studies published from the year 2009. The majority of the included studies (93.16%) assessed impact of nanoparticles on human health, and 95.7% used experimental study design. This shows a clear gap exists in examining the impact of nanoparticles on the environment.
Breast cancer is the second leading cause of death all over the world and is not only limited to females but also affects males. For estrogen receptor-positive breast cancer, tamoxifen has been considered the gold-line therapy for many decades. However, due to the side effects associated with the use of tamoxifen, its use is only limited to individuals in high-risk groups and limits its clinical application to moderate and/or lower-risk groups. Thus, there is a necessity to decrease the dose of tamoxifen, which can be achieved by targeting the drug to breast cancer cells and limiting its absorption to other body parts.
Artificial antioxidants used in the formulation preparation are assumed to upsurge the risk of cancer and liver damage in humans. The need of the hour is to explore bioefficient antioxidants from natural plant sources as they are safer and additionally possess antiviral, anti-inflammatory, and anticancer properties.
The objective of this hypothesis is to prepare tamoxifen-loaded PEGylated NiO nanoparticles using green chemistry, tumbling the toxic effects of the conventional method of synthesis for targeted delivery to breast cancer cells.
The significance of the work is to hypothesize a green method for the synthesis of NiO nanoparticles that are eco-friendly, cost-effective, decrease multidrug resistance, and can be used for targeted therapy. Garlic extract contains an organosulfur compound (Allicin) which has drug-metabolizing, anti-oxidant, and tumour growth inhibition effects. In breast cancer, allicin sensitizes estrogen receptors, increasing the anticancer efficacy of tamoxifen and reducing offsite toxicity. Thus, this garlic extract would act as a reducing agent and a capping agent. The use of nickel salt can help in targeted delivery to breast cancer cells and, in turn, reduces drug toxicity in different organs.
This novel strategy may aim for cancer management with less toxic agents acting as an apt therapeutic modality.
Nickel and its compounds are widely used in industrial and manufacturing processes. NiCl 2 and Ni(NO 2 ) 2 are two common soluble salts of nickel, and both are toxic to living organisms. In this study, we examined and compared the cytotoxic effects of NiCl 2 and Ni(NO 2 ) 2 on the HEK293T cell line by evaluating cell viability and determining the half-maximal inhibitory concentration (IC 50 ) for each compound. The results of our study indicate that both NiCl2 and Ni(NO 2 ) 2 are cytotoxic to the HEK293T cell line in a dose-dependent manner, and the (IC 50 = 60.484 μg/ml) for nickel chloride and (IC 50 =55.652 μg/ml) for nickel nitrate. Nickel nitrate was slightly more toxic than nickel chloride. Increased cytotoxicity of Ni(NO 2 ) 2 and NiCl 2 should be considered in the assessment of the toxicity of nickel compounds on other cell lines in future studies.
Currently, research on toxic effects of PCP Na is greatly insufficient. The aim of this study is to explore the toxic effects of PCP-Na for better conducting future work on PCP-Na toxicology. For this purpose, S. constricta adults were exposed to PCP-Na for toxicity testing. The results showed that PCP-Na could easily bioaccumulate in S. constricta and significantly affected both phrase I and II metabolism enzymes. Meanwhile, PCP-Na strongly activated antioxidant system and caused PC, LPO and DNA damage. In addition, neurotoxicity and immunotoxicity of PCP-Na was demonstrated in this study. Interestingly, we observed that PCP-Na significantly affected the expression of genes of electron transport chain and induced key enzymes of glycolysis, indicating that PCP-Na may act as an uncoupler of oxidative phosphorylation, interfering with energy supply and causing energy compensation. This study is the first to fully analyze and provide a new perspective on the toxicity of PCP-Na.
Novel breakthroughs and innovative applications of nanotechnology have revolutionized the industrial innovations of the twenty-first century. The exciting potential of nanomaterials continues to fascinate people from all walks of life. Various types of nanomaterials are used in different applications and are currently applied in almost all areas, such as electronics, cosmetics, medical purposes, sporting goods, sunscreens, tires, paints, and aviation, among many others. Therefore, the exposure of humans and all fauna and flora to nanoparticles is inevitable. Nanomaterials, including metal nanoparticles, are being increasingly used for different biological and medical applications. Plasmon-resonant nanoparticles in which free electrons collectively oscillate at the metal surface have been recently used in biological imaging. Metal nanoparticles are potential candidates for novel biocides and antibiotic treatments. The novel properties of nanoparticles, especially the physical properties of size and shape, enable them to penetrate all living organisms easily. The widespread use of nanotechnology raises many serious concerns, such as toxicity and the environmental impact of nanomaterials. More work is required to fully understand the basis of nanoparticle toxicity and ameliorate its adverse effect. This review summarizes the biomedical applications and the molecular mechanisms of nanoparticle toxicity in general and the metal nanoparticles in particular.
In the biomedical area, the interdisciplinary field of nanotechnology has the potential to bring numerous unique applications, including better tactics for cancer detection, diagnosis, and therapy. Nanoparticles (NPs) have been the topic of many research and material applications throughout the last decade. Unlike small-molecule medications, NPs are defined by distinct physicochemical characteristics, such as a large surface-to-volume ratio, which allows them to permeate live cells with relative ease. The versatility of NPs as both therapeutics and diagnostics makes them ideal for a broad spectrum of illnesses, from infectious diseases to cancer. A significant amount of data has been participated in the current scientific publications, emphasizing the concept that NPs often produce reactive oxygen species (ROS) to a larger degree than micro-sized particles. It is important to note that oxidative stress governs a wide range of cell signaling cascades, many of which are responsible for cancer cell cytotoxicity. Here, we aimed to provide insight into the signaling pathways triggered by oxidative stress in cancer cells in response to several types of nanomaterials, such as metallic and polymeric NPs and quantum dots. We discuss recent advances in developing integrated anticancer medicines based on NPs targeted to destroy malignant cells by increasing their ROS setpoint.
Metal oxides (MOs) possess several unique physicochemical properties, including structural, chemical, magnetic, electrical, and thermal characteristics. The versatility of these properties make them potential candidates for several industrial and consumer products. Additionally, due to their excellent bioactivity and biocompatibility, the use of MOs such as TiO2, ZnO, Fe2O3, and CeO2 is currently undergoing a dramatic expansion in biomedical applications. Dental implants, drug delivery, bioimaging, biosensor, and antimicrobial agents are just a few examples of their diverse applications. This chapter emphasizes the mechanisms of bioactivity, biocompatibility, and biomedical applications of MOs. Furthermore, MO nanoparticles are the most produced nanoparticles industrially. The extensive utilization of MO nanoparticles confers a potential risk of human exposure and environmental release that clearly raises health concerns. Nanoparticles have higher chemical and physical activities than their bulk states, such as adsorption ability, ion release, and reactive oxygen species production, which could include toxic effects on biological systems. Therefore an overview of the toxicity (in vitro and in vivo) of some of the most important MOs has also been discussed here.
Targeted drug delivery is an advanced method that increases the concentration of drug in the specific targeted area in the body. It improves efficacy of treatment and reduces the side effects in drug administration. The use of nanoparticles enhances the bioavailability, in vivo stability, intestinal absorption, solubility, sustained and targeted delivery. Quercetin (Q) is an anticancer agent used in cancer models due to its antioxidant and antitumor properties. Folic acid (FA) is the ligand used to activate receptor mediated endocytosis for targeted delivery of Quercetin. Polydopamine (PD) is pH sensitive and also inhibits angiogenesis. The quinones of PD serves as anchoring points for FA conjugation. In this work, honeycomb structured Nickel oxide (NiO) nanoparticles loaded with quercetin, surface modified with FA and PD was synthesized to target triple negative breast cancer cells. NiO was characterized by XRD, FTIR, Raman Spectroscopy, BET analysis and Zeta Potential. The honeycomb structure was confirmed by SEM. NiO size and morphology was analyzed by TEM. The porous structure of NiO enabled the efficient loading of Quercetin. Hemolysis analysis showed NiO has good hemocompatibility. The drug release profile confirmed a pH sensitive and controlled delivery of Quercetin. The drug release profile expressed higher release at lower pH. The drug release kinetic profile unveils the primary release mechanism to be diffusion controlled. MTT assay were performed against Vero cell line and MDA-MB-231 breast cancer cell line. The nanoformulation showed reduced cytotoxicity and good biocompatibility on Vero cells and appreciable anti-cancer activity on MDA-MB-231 breast cancer cell line.
Background and Objectives: Despite the many applications of nickel oxide nanoparticles (Nio NPs) in industry and biomedicine, limited studies have been performed in the case of the cytotoxicity of these nanoparticles onnervous system yet. In many neurobiological studies, the human neuroblastoma cells (SH-SY5Y) wich have the ability to become adult human neurons have been used. The aim of the present study was to evaluate the cytotoxicity effects of nickel oxide nanoparticles on human neuroblastoma cell line (SH-SY5Y) in vitro.
Methods: The effect of different doses of NiO NPs (0, 1, 10, 20, 50, 100 μg/ml) on SH-SY5Y cell line was determined by MTT, lactate dehydrogenase (LDH), and caspase-3 activity tests. Statistical analysis was performed by using SPSS software and student t-test.
Results: Based on the results of MTT test, the viability rate of SH-SY5Y cells were decreased dose dependently after 24 hours treatment with NiO NPs, compared with control group. While there was no significant increase in levels of LDH enzyme compared with control group. The activity of caspase-3 enzyme was also significantly increased in a dose dependent pattern of nanoparticles.
Conclusion: The results of the present study showed that the Nickel oxide nanoparticles do not cause membrane damage in SH-SY5Y cells. While these nanoparticles induce their toxic effects by damaging the mitochondrial membrane, increasing the caspase 3 activity, and activating the apoptotic pathway.
Objective
Multiple applications of nickel nanoparticles in industrial, commercial and pharmaceutical processes raise serious health concerns. Although nanomedicine-based therapies directed towards liver have been successfully developed, information on its system toxicity is yet to be gathered. The purpose of present study is to determine and compare hepatotoxicity of nickel oxide nanoparticles and microparticles in rats.Methods
Male Wistar rats were subjected to 5mg/kg/bw of NiONP and NiOMP for two time periods, i.e. 15 and 30 days. Liver function changes (serum enzymes), histopathological observations and parameters of oxidative stress (MDA, H2O2, NO, GSH, catalase and glutathione peroxidase) were studied in respective groups of rats.ResultsOverall results indicated that toxic effects of NiONPs were significantly different and severe than those obtained in NiOMP-treated rats. Further longer exposure induced much severe effects than the shorter exposure.Conclusion
Internalization, accumulation, consequent generation of ROS, oxidative stress and fibrosis manifested into hepatotoxicity of NiONPs. These effects need to be considered whilst making chemotherapeutic use of nickel nanoparticles.
Pacific abalone, Haliotis discus hannai (mean length 2.92 ± 0.5 cm, and mean weight 2.63 ± 0.4 g) were exposed to different concentrations of waterborne nickel (0, 100, 200, and 400 μg/L) at 18, 22, and 26 °C for 2 weeks. The exposure concentration of Ni induced a significant Ni accumulation in specific tissues of H. discus hannai depending on water temperature. The order of nickel accumulation in tissues was hepatopancreas > gill ≈ digestive gland > muscle. Regarding antioxidant response indicators, the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in the hepatopancreas and gill tissues of H. discus hannai was significantly increased by the waterborne nickel exposure depending on water temperature. These results suggest that waterborne nickel exposure can induce a considerable nickel accumulation in specific tissues and stimulation of enzymatic antioxidant systems in Pacific abalone, H. discus hannai Ino, 1953 depending on water temperature.
The exceptional physical and chemical properties of nickel nanomaterials have been exploited in a range of applications such as electrical conductors, batteries, and biomaterials. However, it has been suggested that these unique properties may allow for increased bioavailability, bio-reactivity, and potential adverse health effects. Thus, the purpose of this review was to critically evaluate data regarding the toxicity of oxidic nickel nanoparticles (nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) nanoparticles) with respect to: (1) physico-chemistry properties; (2) nanomaterial characterization in the defined delivery media; (3) appropriateness of model system and translation to potential human effects; (4) biodistribution, retention, and clearance; (5) routes and relevance of exposure; and (6) current research data gaps and likely directions of future research. Inhalation studies were prioritized for review as this represents a potential exposure route in humans. Oxidic nickel particle size ranged from 5 to 100 nm in the 60 studies that were identified. Inflammatory responses induced by exposure of oxidic nickel nanoparticles via inhalation in rodent studies was characterized as acute in nature and only displayed chronic effects after relatively large (high concentration and long duration) exposures. Furthermore, there is no evidence, thus far, to suggest that the effects induced by oxidic nickel nanoparticles are related to preneoplastic events. There are some data to suggest that nano- and micron-sized NiO particles follow a similar dose response when normalized to surface area. However, future experiments need to be conducted to better characterize the exposure–dose–response relationship according to specific surface area and reactivity as a dose metric, which drives particle dissolution and potential biological responses.
The present study, evaluate the anti-cancer properties of nickel oxide nanoparticles functionalized by glutamic acid and conjugated with thiosemicarbazide (NiO@Glu/TSC). First, the NiO@Glu/TSC nanoparticles were prepared using co-condensation reaction. Different techniques were achieved for confirming the synthesized nanoparticles such as Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and energy-dispersive X-ray spectroscopy (EDS), DLS (dynamic light scattering) and ZP (zeta potential) analysis. Interestingly, the transmission electron microscopy (TEM) and scanning electron microscopy (SEM) results indicated that the structure and size of NiO@Glu/TSC nanoparticles were spherical ranging from 20 to 80 nm. NiO@Glu/TSC nanoparticles revealed significant growth inhibition of MCF-7 (human breast cancer) cells with IC50 values of 298.33 μg/mL, while no significant toxicity was evaluated in HEK293 (normal human embryonic kidney) cells after using in vitro toxicity method. Compared with HEK293 cells, MCF-7 cells elucidated a higher sensitivity to NiO@Glu/TSC nanoparticles. To determine the induction of apoptosis or necrosis, cells were double stained with fluorescein isothiocyanate (FITC)-Annexin V and Propidium Iodide (PI) and assessed by flow cytometry. Moreover, to elucidate the nuclear change through apoptosis, Hoechst 33258 staining was examined to investigate morphological features in the nuclei of MCF-7 cells. The results firmly suggest that NiO@Glu/TSC nanoparticles can be as a potential therapeutic agent for cancer treatment.
Nanomaterials (NMs) generally display fascinating physical and chemical properties
that are not always present in bulk materials; therefore, any modification to their size,
shape, or coating tends to cause significant changes in their chemical/physical and
biological characteristics. The dramatic increase in efforts to use NMs renders the risk
assessment of their toxicity highly crucial due to the possible health perils of this
relatively uncharted territory. The different sizes and shapes of the nanoparticles are
known to have an impact on organisms and an important place in clinical applications.
The shape of nanoparticles, namely, whether they are rods, wires, or spheres, is a
particularly critical parameter to affect cell uptake and site-specific drug delivery,
representing a significant factor in determining the potency and magnitude of the
effect. This review, therefore, intends to offer a picture of research into the toxicity
of different shapes (nanorods, nanowires, and nanospheres) of NMs to in vitro and
in vivo models, presenting an in-depth analysis of health risks associated with exposure to such nanostructures and benefits achieved by using certain model organisms
in genotoxicity testing. Nanotoxicity experiments use various models and tests, such
as cell cultures, cores, shells, and coating materials. This review article also attempts
to raise awareness about practical applications of NMs in different shapes in biology,
to evaluate their potential genotoxicity, and to suggest approaches to explain underlying mechanisms of their toxicity and genotoxicity depending on nanoparticle shape.
In order to investigate whether or not dispersed nanoparticles have an effect of inflammation and fibrosis on animals, we developed a nanoparticle generation system and examined the gene expression of matrix metalloproteinase (MMP) and tissue inhibitor matrix proteinase (TIMP) in rat lung containing inhaled nickel oxide (NiO) or titanium dioxide (TiO(2)) nanoparticles. In both experiments, Wistar male rats were exposed to NiO or TiO(2) nanoparticles for 4 wk (6 h/day). The geometric mean diameters of NiO and TiO(2) in the chamber were 139 ± 12 nm and 51 ± 9 nm, respectively. The average concentration of the particle number of NiO and TiO(2) was 1.0E+05 /cm(3) and 2.8E+05 /cm(3), respectively. At 4 d, 1 and 3 months after the end of the inhalation, the rats exposed to these particles were sacrificed and the gene expressions of MMP-2, TIMP-2 and type I collagen were measured using RT-PCR. Pathological finding revealed that there was minimum inflammation with nickel oxide only at 4 d and no change with titanium oxide. However, there were no changes of the gene expression of MMP-2, TIMP-2, and type I collagen in either the NiO or TiO(2) exposure groups. In this study, inhalation of nickel oxide and titanium dioxide nanoparticles did not induce the gene expression of MMP-2 and TIMP-2 mRNA in rat lungs.
Cholangiocarcinoma (CCA) is a tumor with poor prognosis that is resistant to all currently available treatments. Whether curcumin, a nutraceutical derived from turmeric (Curcuma longa), has potential therapeutic activity against human CCA was investigated using three CCA cell lines (KKU100, KKU-M156 and KKU-M213). Examination of mitochondrial dehydrogenase activity, phosphatidylserine externalization, esterase staining, caspase activation and poly-adenosine diphosphate ribose polymerase cleavage demonstrated that curcumin inhibited proliferation of and induced apoptosis in these biliary cancer cells. Colony-formation assay confirmed the growth-inhibitory effect of curcumin on CCA cells. When examined for the mechanism, curcumin was found to activate multiple cell signaling pathways in these cells. First, all CCA cells exhibited constitutively active nuclear factor (NF)-κB, and treatment with curcumin abolished this activation as indicated by DNA binding, nuclear translocation and p65 phosphorylation. Second, curcumin suppressed activation of signal transducer and activator of transcription-3 as indicated by decreased phosphorylation at both tyrosine(705) and serine(727) and inhibition of janus kinase-1 phosphorylation. Third, curcumin induced expression of peroxisome proliferator-activated receptor gamma. Fourth, curcumin upregulated death receptors, DR4 and DR5. Fifth, curcumin suppressed the Akt activation pathway. Sixth, curcumin inhibited expression of cell survival proteins such as B-cell lymphoma-2, B-cell leukemia protein xL, X-linked inhibitor of apoptosis protein, c-FLIP, cellular inhibitor of apoptosis protein (cIAP)-1, cIAP-2 and survivin and proteins linked to cell proliferation, such as cyclin D1 and c-Myc. Seventh, the growth inhibitory effect of curcumin was enhanced in the IκB kinase-deficient cells, the enzyme required for nuclear factor-kappaB activation. Overall, our results indicate that curcumin mediates its antiproliferative and apoptotic effects through activation of multiple cell signaling pathways, and thus, its activity against CCA should be further investigated.
Nickel oxide (NiO) is an important industrial material, and it is also a harmful agent. The toxicity of NiO is size-related: nanoparticles are more toxic than fine-particles. The toxic mechanism induced by NiO nanoparticles remains unexplained, and the relationship between in vitro and in vivo NiO toxicity results is unclear. In the present study, we focused on the oxidative stress caused by NiO nanoparticles by examining and comparing in vitro and in vivo acute responses induced by NiO nanoparticles.
Cellular responses induced by black NiO nanoparticles with a primary particle size of 20 nm, were examined in human lung carcinoma A549 cells. In vivo responses were examined by instillation of NiO nanoparticles into rat trachea. Bronchoalveolar lavage fluid (BALF) was collected after intratracheal instillation at different time points, and concentrations of lipid peroxide heme oxygenase-1 (HO-1), surfactant protein-D (SP-D) and lactate dehydrogenase (LDH) in BALF were measured.
The levels of intracellular reactive oxygen species and lipid peroxidation in A549 cells increased with increasing exposure to NiO nanoparticles, and increases in gene expressions of HO-1 and SP-D were observed in A549 cells. The lipid peroxide level in BALF significantly increased after 24 h instillation but decreased three days later. LDH leakage was also observed three days later.
NiO nanoparticles induce oxidative stress-related lung injury. In vivo and in vitro oxidative stress was induced resulting in activation of antioxidant systems. Based on these responses, we conclude that the results of the in vivo and in vitro studies tend to correspond.
Adverse effects of manufactured nickel oxide nanoparticles on the microalgae Chlorellavulgaris were determined by algal growth-inhibition test and morphological observation via transmission electron microscopy (TEM). Results showed that the NiO nanoparticles had severe impacts on the algae, with 72 h EC(50) values of 32.28 mg NiOL(-1). Under the stress of NiO nanoparticles, C. vulgaris cells showed plasmolysis, cytomembrane breakage and thylakoids disorder. NiO nanoparticles aggregated and deposited in algal culture media. The presence of algal cells accelerated aggregation of nanoparticles. Moreover, about 0.14% ionic Ni was released when NiO NPs were added into seawater. The attachment of aggregates to algal cell surface and the presence of released ionic Ni were likely responsible for the toxic effects. Interestingly, some NiO nanoparticles were reduced to zero valence nickel as determined by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analysis. The maximum ratios of nickel reduction was achieved at 72 h of exposure, in accordance with the time-course of changes in soluble protein content of treated C. vulgaris, implying that some proteins of algae are involved in the process. Our results indicate that the toxicity and bioavailability of NiO nanoparticles to marine algae are reduced by aggregation and reduction of NiO. Thus, marine algae have the potential for usage in nano-pollution bio-remediation in aquatic system.
Development of fast and sensitive sensors for glucose determination is important in food industry, clinic diagnostics, biotechnology and many other areas. In these years, considerable attention has been paid to develop non-enzymatic electrodes to solve the disadvantages of the enzyme-modified electrodes, such as instability, high cost, complicated immobilization procedure and critical operating situation et al. Nano nickel oxide (NiO) modified non-enzymatic glucose sensors with enhanced sensitivity were investigated. Potential scanning nano NiO modified carbon paste electrodes up to high potential in alkaline solution greatly increases the amount of redox couple Ni(OH)(2)/NiOOH derived from NiO, and thus improves their electrochemical properties and electrocatalytical performance toward the oxidation of glucose. The non-enzymatic sensors response quickly to glucose and the response time is less than 5s, demonstrating excellent electrocatalytical activity and assay performance. The calibration plot is linear over the wide concentration range of 1-110 μM with a sensitivity of 43.9 nA/μM and a correlation coefficient of 0.998. The detection limit of the electrode was found to be 0.16 μM at a signal-to-noise ratio of 3. The proposed non-enzymatic sensors can be used for the assay of glucose in real sample.
Extensive research during the past 2 decades has revealed the mechanism by which continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer, diabetes, and cardiovascular, neurological, and pulmonary diseases. Oxidative stress can activate a variety of transcription factors including NF-κB, AP-1, p53, HIF-1α, PPAR-γ, β-catenin/Wnt, and Nrf2. Activation of these transcription factors can lead to the expression of over 500 different genes, including those for growth factors, inflammatory cytokines, chemokines, cell cycle regulatory molecules, and anti-inflammatory molecules. How oxidative stress activates inflammatory pathways leading to transformation of a normal cell to tumor cell, tumor cell survival, proliferation, chemoresistance, radioresistance, invasion, angiogenesis, and stem cell survival is the focus of this review. Overall, observations to date suggest that oxidative stress, chronic inflammation, and cancer are closely linked.
Oxidative stress regulates dysfunction and senescence of vascular endothelial cells. The DNA damage response and its main signaling pathway involving ataxia telangiectasia mutated (ATM) have been implicated in playing a central role in mediating the actions of oxidative stress; however, the role of the ATM signaling pathway in vascular pathogenesis has largely remained unclear. Here, we identify ATM to regulate oxidative stress-induced endothelial cell dysfunction and premature senescence. Oxidative stress induced senescence in endothelial cells through activation/phosphorylation of ATM by way of an Akt/p53/p21-mediated pathway. These actions were abrogated in cells in which ATM was knocked down by RNA interference or inhibited by specific inhibitory compounds. Furthermore, the in vivo significance of this regulatory pathway was confirmed using ATM knock-out mice in which induction of senescent endothelial cells in the aorta in a diabetic mouse model of endothelial dysfunction and senescence was attenuated in contrast to pathological changes seen in wild-type mice. Collectively, our results show that ATM through an ATM/Akt/p53/p21-dependent signaling pathway mediates an instructive role in oxidative stress-induced endothelial dysfunction and premature senescence.
In this work we describe the synthesis, micro structure (XRD, SEM) and EPR of NiO nanoparticles synthesized by urea-based combustion method using Ni nitrate as the source of Ni. We used fuel-to-oxidizer ratio (psi) as a control parameter to investigate how lattice parameter, particle size and EPR susceptibility vary with psi = 0.25 to 2. Earlier we have studied NiO as a substitutional solute in MgO. The average particle size of NiO was estimated from the full width half maximum (gaussian and lorentzian fits) of the X-ray diffraction peaks of powders using Sherrer's formula and Williamson-Hall plot. The particle size varies from 7 nm to 38 nm as psi is varied systematically. The surface areas were measured using BET method. FT-IR confirms the Ni-O crystalline bond formation. We also calculated porosity and strain in the NiO nanoparticles with varying psi. EPR spectra have yielded the susceptibility of the NiO nanoparticles. Band gap of NiO was determined by UV-visible absorption edge.
Members of the caspase family of cysteine proteases play central roles in coordinating the stereotypical events that occur during apoptosis. Because the major executioner caspases, caspase-3 and caspase-7, exhibit almost indistinguishable activity toward certain synthetic peptide substrates, this has led to the widespread view that these proteases occupy functionally redundant roles within the cell death machinery. However, the distinct phenotypes of mice deficient in either of these caspases, as well as mice deficient in both, is at odds with this view. These distinct phenotypes could be related to differences in the relative expression levels of caspase-3 and caspase-7 in vivo, or due to more fundamental differences between these proteases in terms of their ability to cleave natural substrates. Here we show that caspase-3 and caspase-7 exhibit differential activity toward multiple substrate proteins, including Bid, XIAP, gelsolin, caspase-6, and cochaperone p23. Caspase-3 was found to be generally more promiscuous than caspase-7 and appears to be the major executioner caspase during the demolition phase of apoptosis. Our observations provide a molecular basis for the different phenotypes seen in mice lacking either caspase and indicate that these proteases occupy nonredundant roles within the cell death machinery.
• apoptosis
• caspase substrates
• proteolysis
Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly
being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and
drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions
with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same
composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable
results of these capabilities are harmful interactions with biological systems and the environment, with the potential to
generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials
in the marketplace is urgently required and achievable.
The present study investigates the protective effects of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity using various animal models with biochemical parameters like serum marker enzymes and antioxidants in target tissues. In addition, liver and cardiac histoarchitecture changes were also studied. Curcumin treatment inhibited carrageenin and albumin induced edema, cotton pellet granuloma formation. The increased relative weight of liver and heart in CCl(4) induced liver injury and isoproterenol induced cardiac necrosis were also reduced by curcumin treatment. Elevated serum marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) increased lipid peroxidation, decreased gluthione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in edematous, granulomatus, liver and heart tissues during inflammation, liver injury and cardiac necrosis, respectively. Curcumin treatment reversed all these above mentioned biochemical changes significantly in all animal models studied. Even histoarchitecture alterations observed in liver injury and cardiac necrosis observed were partially reversed (improved) by curcumin treatments. In in vitro experiments too curcumin inhibited iron catalyzed lipid peroxidation in liver homogenates, scavenged nitric oxide spontaneously generated from nitroprusside and inhibited heat induced hemolysis of rat erythrocytes. The present in vitro and in vivo experimental findings suggest the protective effect of curcumin on experimentally induced inflammation, hepatotoxicity, and cardiotoxicity in rats.
Oxidative stress (OS) has been implicated in various degenerative diseases in aging. In an attempt to quantify OS in a cell model, we examined OS induced by incubating for 30 min with various free radical generators in PC12 cells by using the dichlorofluorescein (DCF) assay, modified for use by a fluorescent microplate reader. The nonfluorescent fluorescin derivatives (dichlorofluorescin, DCFH), after being oxidized by various oxidants, will become DCF and emit fluorescence. By quantifying the fluorescence, we were able to quantify the OS. Our results indicated that the fluorescence varied linearly with increasing concentrations (between 0.1 and 1 mM) of H2O2 and 2,2′-azobios(2-amidinopropane) dihydrochloride (AAPH; a peroxyl radical generator). By contrast, the fluorescence varied as a nonlinear response to increasing concentrations of 3-morpholinosydnonimine hydrochloride (SIN-1; a peroxynitrite generator), sodium nitroprusside (SNP; a nitric oxide generator), and dopamine. Dopamine had a biphasic effect; it decreased the DCF fluorescence, thus acting as an antioxidant, at concentrations
A sensitive quantitative procedure for assaying viable cells in monolayer cultures is described. The two-component test involves (a) microscopic screening for morphological alterations after an experimental protocol for cytotoxicity studies and (b) quantitation of surviving cells by incubation with the supravital dye neutral red, followed by colorimetric analysis of the dye extracted from the lysosomes of the viable cells. Both assays, conveniently carried out within the same culture, have been standardized for use with 96-well microtiter plates and automatic reading with a Dynatech spectrophotometric microplate reader. The test can be adapted for use with conventional spectrophotometers.
Metal oxide nanoparticles are often used as industrial catalysts and elevated levels of these particles have been clearly demonstrated at sites surrounding factories. To date, limited toxicity data on metal oxide nanoparticles are available. To understand the impact of these airborne pollutants on the respiratory system, airway epithelial (HEp-2) cells were exposed to increasing doses of silicon oxide (SiO2), ferric oxide (Fe2O3) and copper oxide (CuO) nanoparticles, the leading metal oxides found in ambient air surrounding factories. CuO induced the greatest amount of cytotoxicity in a dose-dependent manner; while even high doses (400 μg/cm2) of SiO2 and Fe2O3 were non-toxic to HEp-2 cells. Although all metal oxide nanoparticles were able to generate ROS in HEp-2 cells, CuO was better able to overwhelm antioxidant defenses (e.g. catalase and glutathione reductase). A significant increase in the level of 8-isoprostanes and in the ratio of GSSG to total glutathione in cells exposed to CuO suggested that ROS generated by CuO induced oxidative stress in HEp-2 cells. Co-treatment of cells with CuO and the antioxidant resveratrol increased cell viability suggesting that oxidative stress may be the cause of the cytotoxic effect of CuO. These studies demonstrated that there is a high degree of variability in the cytotoxic effects of metal oxides, that this variability is not due to the solubility of the transition metal, and that this variability appears to involve sustained oxidative stress possibly due to redox cycling.
Due to the interesting magnetic and electrical properties with good chemical and thermal stabilities, nickel ferrite nanoparticles are being utilized in many applications including magnetic resonance imaging, drug delivery and hyperthermia. Recent studies have shown that nickel ferrite nanoparticles produce cytotoxicity in mammalian cells. However, there is very limited information concerning the toxicity of nickel ferrite nanoparticles at the cellular and molecular level. The aim of this study was to investigate the cytotoxicity, oxidative stress and apoptosis induction by well-characterized nickel ferrite nanoparticles (size 26 nm) in human lung epithelial (A549) cells. Nickel ferrite nanoparticles induced dose-dependent cytotoxicity in A549 cells demonstrated by MTT, NRU and LDH assays. Nickel ferrite nanoparticles were also found to induce oxidative stress evidenced by generation of reactive oxygen species (ROS) and depletion of antioxidant glutathione (GSH). Further, co-treatment with the antioxidant L-ascorbic acid mitigated the ROS generation and GSH depletion due to nickel ferrite nanoparticles suggesting the potential mechanism of oxidative stress. Quantitative real-time PCR analysis demonstrated that following the exposure of A549 cells to nickel ferrite nanoparticles, the level of mRNA expressions of cell cycle checkpoint protein p53 and apoptotic proteins (bax, caspase-3 and caspase-9) were significantly up-regulated, whereas the expression of anti-apoptotic proteins (survivin and bcl-2) were down-regulated. Moreover, activities of caspase-3 and caspase-9 enzymes were also significantly higher in nickel ferrite nanoparticles exposed cells. To the best of our knowledge this is the first report showing that nickel ferrite nanoparticles induced apoptosis in A549 cells through ROS generation and oxidative stress via p53, survivin, bax/bcl-2 and caspase pathways.
Nickel nanoparticle (Ni NP) is increasingly used in modern industries such as catalysts, sensors and electronic applications. Due to wide-spread industrial applications the inhalation is the primary source of exposure to Ni NPs. However, data demonstrating the effect of Ni NPs on the pulmonary system remain scarce. The present study was designed to examine the toxic effect of human lung epithelial A549 cells treated with well characterized Ni NPs at the concentrations of 0, 1, 2, 5, 10 and 25 μg/ml for 24 and 48 h. Mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH), reactive oxygen species (ROS), membrane lipid peroxidation (LPO) and caspase-3 activity were assessed as toxicity end points. Results showed that Ni NPs reduced mitochondrial function and induced the leakage of LDH in dose and time-dependent manner. Ni NPs were also found to induce oxidative stress in dose and time-dependent manner indicated by depletion of GSH and induction of ROS and LPO. Further, activity of caspase-3 enzyme, marker of apoptosis was significantly higher in treated cells with time and Ni NPs dosage. The results exhibited significant toxicity of Ni NPs in human lung epithelial A549 cells which is likely to be mediated through oxidative stress. This study warrants more careful assessment of Ni NPs before their industrial applications.
In this study, the microbial toxicities of metal oxide nanoparticles were evaluated for Escherichia coli, Bacillus subtilis, and Streptococcus aureus in laboratory experiments. The nanoparticles tested were CuO, NiO, ZnO, and Sb(2)O(3). The metal oxide nanoparticles were dispersed thoroughly in a culture medium, and the microorganisms were cultivated on Luria-Bertani agar plates containing different concentrations of metal oxide nanoparticles. The bacteria were counted in terms of colony forming units (CFU). The CFU was reduced in a culture medium containing metal oxide NP, and the dose-response relationship was characterized. CuO nanoparticles were found to be the most toxic among the tested nanoparticles, followed by ZnO (except S. aureus), NiO, and Sb(2)O(3) nanoparticles. We determined that the intrinsic toxic properties of heavy metals are also associated with the toxicity of metal oxide nanoparticles. Ion toxicity was also evaluated to determine the effects of metal ions dissolved from metal oxide NPs, and the toxicity induced from the dissolved ions was determined to be negligible herein. To the best of our knowledge, this is the first study of the toxicity of NiO and Sb(2)O(3) NPs on microorganisms. We also discuss the implications of our findings regarding the effects of the intrinsic toxic properties of heavy metals, and concluded that the apparent toxicities of metal oxide NPs can largely be understood as a matter of particle toxicity.
Doxorubicin (DOX) is a widely used chemotherapy agent. The major adverse effect of DOX treatment in cancer patients is the onset of cardiomyopathy and heart failure. Reactive oxygen species (ROS) are proposed to be responsible for DOX cardiotoxicity. Curcumin, a natural compound extracted from Curcuma Longa L., is known for its anti-oxidant properties. It has been identified as increased apoptosis in several cancer cell lines in combination with doxorubicin, but there are few studies about the effect of curcumin and doxorubicin on normal cardiac cells. Therefore, we evaluated the effects of curcumin on apoptosis induced by DOX in cardiac muscle cells. Pretreatment with curcumin significantly increased DOX-induced apoptosis of cardiac muscle cells through down regulation of Bcl-2, up-regulation of caspase-8 and caspase-9. The Bax/Bcl-2 ratio increased significantly after 1h pretreatment with curcumin. As well, curcumin increases ROS generation by DOX. In response to DOX, NF-κB was activated. However, curcumin was able to inhibit NF-κB activation. In conclusion, our results indicated that pretreatment with nontoxic concentrations of curcumin sensitized H9c2 cells to DOX-mediated apoptosis by generation of ROS.
Nanotechnology is rapidly growing with nanoparticles produced and utilized in a wide range of commercial products throughout the world. For example, silver nanoparticles (Ag NP) are used in electronics, bio-sensing, clothing, food industry, paints, sunscreens, cosmetics and medical devices. These broad applications, however, increase human exposure and thus the potential risk related to their short- and long-term toxicity. A large number of in vitro studies indicate that Ag NPs are toxic to the mammalian cells derived from skin, liver, lung, brain, vascular system and reproductive organs. Interestingly, some studies have shown that this particle has the potential to induce genes associated with cell cycle progression, DNA damage and apoptosis in human cells at non-cytotoxic doses. Furthermore, in vivo bio-distribution and toxicity studies in rats and mice have demonstrated that Ag NP administered by inhalation, ingestion or intra-peritoneal injection were subsequently detected in blood and caused toxicity in several organs including brain. Moreover, Ag NP exerted developmental and structural malformations in non-mammalian model organisms typically used to elucidate human disease and developmental abnormalities. The mechanisms for Ag NP induced toxicity include the effects of this particle on cell membranes, mitochondria and genetic material. This paper summarizes and critically assesses the current studies focusing on adverse effects of Ag NPs on human health.
Copper oxide nanoparticles (CuO NPs) are increasingly used in various applications. Recent studies suggest that oxidative stress may be the cause of the cytotoxicity of CuO NPs in mammalian cells. However, little is known about the genotoxicity of CuO NPs following exposure to human cells. This study was undertaken to investigate CuO NPs induced genotoxic response through p53 pathway in human pulmonary epithelial cells (A549). In addition, cytotoxicity and oxidative stress markers were also assessed. Results showed that cell viability was reduced by CuO NPs and degree of reduction was dose dependent. CuO NPs were also found to induce oxidative stress in dose-dependent manner indicated by depletion of glutathione and induction of lipid peroxidation, catalase and superoxide dismutase. The expression of Hsp70, the first tier biomarker of cellular damage was induced by CuO NPs. Further, CuO NPs up-regulated the cell cycle checkpoint protein p53 and DNA damage repair proteins Rad51 and MSH2 expression. These results demonstrate that CuO NPs possess a genotoxic potential in A549 cells which may be mediated through oxidative stress. Our short-term exposure study of high level induction of genotoxic response of CuO NPs will need to be further investigated to determine whether long-term exposure consequences may exist for CuO NPs application.
Toxicological studies at environmentally relevant concentrations are essential for understanding ecotoxic and health risks of pollutants such as polybrominated diphenyl ethers (PBDEs). However, no information is available on what exposure levels of PBDEs in vitro studies are environmentally relevant. We exposed MCF-7, HepG2, H295R and PC12 cells to BDE-47, and measured BDE-47 concentrations in the cells after exposure. We also used the percentile method to summarize literature data on environmental exposure levels of biotic tissues to PBDEs. The exposure concentration that resulted in a BDE-47 burden in cells close to the 90th percentile of PBDEs levels in tissues was assigned as the upper limit for the environmentally relevant concentration. Exposure to 1nM BDE-47 resulted in PBDEs burdens in MCF-7, HepG2 and H295R cells close to the 90th percentile but PBDEs burdens in PC12 cells were higher than the 90th percentile. In consideration of the high exposure levels in PBDE-polluted areas, we concluded that the highest environmentally relevant exposure concentration of PBDEs in culture media should be approximately 10nM for MCF-7, HepG2 and H295R cells, and<10nM for PC12 cells. These results provide an approximate reference for setting environmentally relevant exposure concentrations of PBDEs for studies in vitro.
Nanoparticles are being widely investigated for a range of applications due to their unique physical properties. For example, silver nanoparticles are used in commercial products for their antibacterial and antifungal properties. Some of these products are likely to result in silver nanoparticles reaching the aquatic environment. As such, nanoparticles pose a health concern for humans and aquatic species. We used a medaka (Oryzias latipes) cell line to investigate the cytotoxicity and genotoxicity of 30nm diameter silver nanospheres. Treatments of 0.05, 0.3, 0.5, 3 and 5microg/cm(2) induced 80, 45.7, 24.3, 1 and 0.1% survival, respectively, in a colony forming assay. Silver nanoparticles also induced chromosomal aberrations and aneuploidy. Treatments of 0, 0.05, 0.1 and 0.3microg/cm(2) induced damage in 8, 10.8, 16 and 15.8% of metaphases and 10.8, 15.6, 24 and 24 total aberrations in 100 metaphases, respectively. These data show that silver nanoparticles are cytotoxic and genotoxic to fish cells.
Due to the intensive commercial application of silver nanoparticles (Ag NPs), risk assessment of this nanoparticle is of great importance. Our previous in vitro study demonstrated that Ag NPs caused DNA damage and apoptosis in mouse embryonic stem cells and fibroblasts. However, toxicity of Ag NPs in vivo is largely lacking. This study was undertaken to examine the toxic effects of well-characterized polysaccharide coated 10 nm Ag NPs on heat shock stress, oxidative stress, DNA damage and apoptosis in Drosophila melanogaster. Third instar larvae of D. melanogaster were fed a diet of standard cornmeal media mixed with Ag NPs at the concentrations of 50 and 100 microg/ml for 24 and 48 h. Ag NPs up-regulated the expression of heat shock protein 70 and induced oxidative stress in D. melanogaster. Malondialdehyde level, an end product of lipid peroxidation was significantly higher while antioxidant glutathione content was significantly lower in Ag NPs exposed organisms. Activities of antioxidant enzyme superoxide dismutase and catalase were also significantly higher in the organisms exposed to Ag NPs. Furthermore, Ag NPs up-regulated the cell cycle checkpoint p53 and cell signaling protein p38 that are involved in the DNA damage repair pathway. Moreover, activities of caspase-3 and caspase-9, markers of apoptosis were significantly higher in Ag NPs exposed organisms. The results indicate that Ag NPs in D. melanogaster induce heat shock stress, oxidative stress, DNA damage and apoptosis. This study suggests that the organism is stressed and thus warrants more careful assessment of Ag NPs using in vivo models to determine if chronic exposure presents developmental and reproductive toxicity.
Stable lyophilisomes of fibrinogen at pH 7.5 have been prepared by the method of a rapid freezing-heating and annealing sequence. Reduction of the lyophilisomes of the nickel-fibrinogen complex coated on solid substrates and subsequent heating showed formation of nickel hydroxide and finally nickel oxide. Ultraviolet-visible spectroscopy has been used to monitor the thin films of pure fibrinogen microcapsules, as well as the subsequent nucleation and growth of nanoparticles within the supramolecular structure. Transmission electron microscopy showed initially a thread-like structure which disappeared on continued heating, resulting in nanoparticles ranging from 10 to 50 nm. Particle-size distribution of product was analyzed by using X-ray diffraction (XRD), transmission electron microscopy (TEM) and the corresponding selected area electron diffraction (SAED), and Brunauer-Emmett-Teller (BET) N(2) adsorption. The results suggest that the NiO particles have a body-centered cubic structure and are well dispersed. The particle-size distribution ranges from 10 to 50 nm with an average particle size about 28 nm, and the specific surface area is 34 m(2)/g. Magnetic study carried out on the prepared nanoparticles showed a ferromagnetic behavior.
Oxidative stress has been implicated in the degeneration of dopaminergic neurons in the substantia nigra of Parkinson's disease patients, and several anti-oxidants have been shown to be effective on the treatment of Parkinson's disease. Curcumin has been previously reported to possess radical scavenger, iron chelating, anti-inflammatory properties in different tissues. The aim of present study is to explore the cytoprotection of curcumin against 6-hydroxydopamine (6-OHDA)-induced neuronal death, as well as the underlying mechanisms in MES23.5 cells. Our results showed that 6-OHDA significantly reduced the cell viability of MES23.5 cells. Curcumin protected MES23.5 cells against 6-OHDA neurotoxicity by partially restoring the mitochondrial membrane potential, increasing the level of Cu-Zn superoxide dismutase and suppressing an increase in intracellular reactive oxygen species. Furthermore, curcumin pretreatment significantly inhibited 6-OHDA induced nuclear factor-kappaB translocation. These results suggest that the neuroprotective effects of curcumin are attributed to the antioxidative properties and the modulation of nuclear factor-kappaB translocation.
With the rapid expansion in the nanotechnology industry, it is essential that the safety of engineered nanomaterials and the factors that influence their associated hazards are understood. A vital area governing regulatory health risk assessment is genotoxicology (the study of genetic aberrations following exposure to test agents), as DNA damage may initiate and promote carcinogenesis, or impact fertility. Of late, considerable attention has been given to the toxicity of engineered nanomaterials, but the importance of their genotoxic potential on human health has been largely overlooked. This comprehensive review focuses on the reported abilities of metal nanoparticles, metal-oxide nanoparticles, quantum dots, fullerenes, and fibrous nanomaterials, to damage or interact with DNA, and their ecogenotoxicity is also considered. Many of the engineered nanomaterials assessed were found to cause genotoxic responses, such as chromosomal fragmentation, DNA strand breakages, point mutations, oxidative DNA adducts and alterations in gene expression profiles. However, there are clear inconsistencies in the literature and it is difficult to draw conclusions on the physico-chemical features of nanomaterials that promote genotoxicity, largely due to study design. Hence, areas that require that further attention are highlighted and recommendations to improve our understanding of the genotoxic potential of engineered nanomaterials are addressed.
Silver nanoparticles (Ag-np) are being used increasingly in wound dressings, catheters, and various household products due to their antimicrobial activity. The toxicity of starch-coated silver nanoparticles was studied using normal human lung fibroblast cells (IMR-90) and human glioblastoma cells (U251). The toxicity was evaluated using changes in cell morphology, cell viability, metabolic activity, and oxidative stress. Ag-np reduced ATP content of the cell caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. DNA damage, as measured by single cell gel electrophoresis (SCGE) and cytokinesis blocked micronucleus assay (CBMN), was also dose-dependent and more prominent in the cancer cells. The nanoparticle treatment caused cell cycle arrest in G(2)/M phase possibly due to repair of damaged DNA. Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis. The transmission electron microscopic (TEM) analysis indicated the presence of Ag-np inside the mitochondria and nucleus, implicating their direct involvement in the mitochondrial toxicity and DNA damage. A possible mechanism of toxicity is proposed which involves disruption of the mitochondrial respiratory chain by Ag-np leading to production of ROS and interruption of ATP synthesis, which in turn cause DNA damage. It is anticipated that DNA damage is augmented by deposition, followed by interactions of Ag-np to the DNA leading to cell cycle arrest in the G(2)/M phase. The higher sensitivity of U251 cells and their arrest in G(2)/M phase could be explored further for evaluating the potential use of Ag-np in cancer therapy.
TNF-alpha and NF-kappaB play important roles in the development of inflammation in chronic renal failure (CRF). In hepatic cells, curcumin is shown to antagonize TNF-alpha-elicited NF-kappaB activation. In this study, we hypothesized that if inflammation plays a key role in renal failure then curcumin should be effective in improving CRF. The effectiveness of curcumin was compared with enalapril, a compound known to ameliorate human and experimental CRF. Investigation was conducted in Sprague-Dawley rats where CRF was induced by 5/6 nephrectomy (Nx). The Nx animals were divided into untreated (Nx), curcumin-treated (curcumin), and enalapril-treated (enalapril) groups. Sham-operated animals served as a control. Renal dysfunction in the Nx group, as evidenced by elevated blood urea nitrogen, plasma creatinine, proteinuria, segmental sclerosis, and tubular dilatation, was significantly reduced by curcumin and enalapril treatment. However, only enalapril significantly improved blood pressure. Compared with the control, the Nx animals had significantly higher plasma and kidney TNF-alpha, which was associated with NF-kappaB activation and macrophage infiltration in the kidney. These changes were effectively antagonized by curcumin and enalapril treatment. The decline in the anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARgamma) seen in Nx animals was also counteracted by curcumin and enalapril. Studies in mesangial cells were carried out to further establish that the anti-inflammatory effect of curcumin in vivo was mediated essentially by antagonizing TNF-alpha. Curcumin dose dependently antagonized the TNF-alpha-mediated decrease in PPARgamma and blocked transactivation of NF-kappaB and repression of PPARgamma, indicating that the anti-inflamatory property of curcumin may be responsible for alleviating CRF in Nx animals.
Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, 1) is a yellow ingredient isolated from turmeric (curcumin longa). Many health benefits have been claimed for curcumin, and these have generally been ascribed to its radical-trapping antioxidant properties. In order to find more active antioxidants with 1 as the lead compound, we synthesized curcumin analogues, i.e., 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (2), 1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (4), 1,7-bis (4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (5), 1,7-bis(3,4-dimethoxyphenyl)-1,6-heptadiene-3,5-dione (6), 1,7-bis(4-methoxyphenyl)-1,6-heptadiene-3,5-dione (7), and 1,7-diphenyl-1,6-heptadiene-3,5-dione (8). Antioxidative effects of curcumin and these analogues against the peroxidation of linoleic acid were studied in sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) micelles. The peroxidation was initiated thermally by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), and reaction kinetics were monitored by the formation of linoleic acid hydroperoxides. Kinetic analysis of the antioxidation process demonstrates that these compounds, except 6, 7 and 8, are effective antioxidants in micelles by H-atom abstraction from the phenolic groups. Compounds 2 and 3, which bear ortho-diphenoxyl functionality, possess significantly higher antioxidant activity than curcumin and other analogues, and the 4-hydroxy-3-methoxyphenyl group also plays an important role in the antioxidative activity. In addition, the synergistic antioxidant effect of these compounds with alpha-tocopherol (vitamin E) in micelles was also studied by following the formation of linoleic acid hydroperoxides and the consumption of alpha-tocopherol. It was found that these compounds could not synergistically interact with alpha-tocopherol in micelles.
Silver nanoparticles (Ag NPs) have recently received much attention for their possible applications in biotechnology and life sciences. Ag NPs are of interest to defense and engineering programs for new material applications as well as for commercial purposes as an antimicrobial. However, little is known about the genotoxicity of Ag NPs following exposure to mammalian cells. This study was undertaken to examine the DNA damage response to polysaccharide surface functionalized (coated) and non-functionalized (uncoated) Ag NPs in two types of mammalian cells; mouse embryonic stem (mES) cells and mouse embryonic fibroblasts (MEF). Both types of Ag NPs up-regulated the cell cycle checkpoint protein p53 and DNA damage repair proteins Rad51 and phosphorylated-H2AX expression. Furthermore both of them induced cell death as measured by the annexin V protein expression and MTT assay. Our observations also suggested that the different surface chemistry of Ag NPs induce different DNA damage response: coated Ag NPs exhibited more severe damage than uncoated Ag NPs. The results suggest that polysaccharide coated particles are more individually distributed while agglomeration of the uncoated particles limits the surface area availability and access to membrane bound organelles.
Publisher Summary This chapter discusses microsomal lipid peroxidation. Lipid peroxidation is a complex process known to occur in both plants and animals. It involves the formation and propagation of lipid radicals, the uptake of oxygen, a rearrangement of the double bonds in unsaturated lipids, and the eventual destruction of membrane lipids, producing a variety of breakdown products, including alcohols, ketones, aldehydes, and ethers. Biological membranes are often rich in unsaturated fatty acids and bathed in an oxygen-rich, metal-containing fluid. Lipid peroxidation begins with the abstraction of a hydrogen atom from an unsaturated fatty acid, resulting in the formation of a lipid radical. The formation of lipid endoperoxides in unsaturated fatty acids containing at least 3 methylene interrupted double bonds can lead to the formation of malondialdehyde as a breakdown product. Nonenzymic peroxidation of microsomal membranes also occurs and is probably mediated in part by endogenous hemoproteins and transition metals. The direct measurement of lipid hydroperoxides has an advantage over the thiobarbituric acid assay in that it permits a more accurate comparison of lipid peroxide levels in dissimilar lipid membranes.
A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
Oxidative stress (OS) has been implicated in various degenerative diseases in aging. In an attempt to quantify OS in a cell model, we examined OS induced by incubating for 30 min with various free radical generators in PC12 cells by using the dichlorofluorescein (DCF) assay, modified for use by a fluorescent microplate reader. The nonfluorescent fluorescin derivatives (dichlorofluorescin, DCFH), after being oxidized by various oxidants, will become DCF and emit fluorescence. By quantifying the fluorescence, we were able to quantify the OS. Our results indicated that the fluorescence varied linearly with increasing concentrations (between 0.1 and 1 mM) of H2O2 and 2,2'-azobios(2-amidinopropane) dihydrochloride (AAPH; a peroxyl radical generator). By contrast, the fluorescence varied as a nonlinear response to increasing concentrations of 3-morpholinosydnonimine hydrochloride (SIN-1; a peroxynitrite generator), sodium nitroprusside (SNP; a nitric oxide generator), and dopamine. Dopamine had a biphasic effect; it decreased the DCF fluorescence, thus acting as an antioxidant, at concentrations <500 microM in cells, but acted as a pro-oxidant by increasing the fluorescence at 1 mM. While SNP was not a strong pro-oxidant, SIN-1 was the most potent pro-oxidant among those tested, inducing a 70 times increase of fluorescence at a concentration of 100 microM compared with control. Collectively, due to its indiscriminate nature to various free radicals, DCF can be very useful in quantifying overall OS in cells, especially when used in conjunction with a fluorescent microplate reader. This method is reliable and efficient for evaluating the potency of pro-oxidants and can be used to evaluate the efficacy of antioxidants against OS in cells.
Curcumin, a widely used spice and coloring agent in food, has been shown to possess potent antioxidant, antitumor promoting and anti-inflammatory properties in vitro and in vivo. The mechanism(s) of such pleiotropic action by this yellow pigment is unknown; whether induction of distinct antioxidant genes contributes to the beneficial activities mediated by curcumin remains to be investigated. In the present study we examined the effect of curcumin on endothelial heme oxygenase-1 (HO-1 or HSP32), an inducible stress protein that degrades heme to the vasoactive molecule carbon monoxide and the antioxidant biliverdin. Exposure of bovine aortic endothelial cells to curcumin (5-15 microM) resulted in both a concentration- and time-dependent increase in HO-1 mRNA, protein expression and heme oxygenase activity. Hypoxia (18 h) also caused a significant (P < 0.05) increase in heme oxygenase activity which was markedly potentiated by the presence of low concentrations of curcumin (5 microM). Interestingly, prolonged incubation (18 h) with curcumin in normoxic or hypoxic conditions resulted in enhanced cellular resistance to oxidative damage; this cytoprotective effect was considerably attenuated by tin protoporphyrin IX, an inhibitor of heme oxygenase activity. In contrast, exposure of cells to curcumin for a period of time insufficient to up-regulate HO-1 (1.5 h) did not prevent oxidant-mediated injury. These data indicate that curcumin is a potent inducer of HO-1 in vascular endothelial cells and that increased heme oxygenase activity is an important component in curcumin-mediated cytoprotection against oxidative stress.
To examine the role of calcium-dependent and -independent proteolytic activity in the globulization of isolated fiber cells and glucose-induced lens opacification.
Fiber cells from rat lens cortex were isolated, and the [Ca(2+)](i) and protease activity in the isolated fibers were determined by using a calcium binding dye and the protease substrate t-butoxycarbonyl-Leu-Met-7-amino-4-chloromethylcoumarin (BOC-Leu-Met-CMAC). The activity of calpain in the lens cortex homogenate was determined with fluorescein-casein in the presence of Ca(2+) and that of fiber cell globulizing aminopeptidase (FCGAP) with BOC-Leu-Met-CMAC and reduced glutathione (GSH) in the absence of Ca(2+). The lens proteases-calpain and the novel aminopeptidase FCGAP were partially purified by diethylaminoethyl (DEAE) gel column chromatography. Single fiber cells were isolated from rat lens, plated on coverslips, and placed in a temperature-controlled chamber. Their globulization time was determined by the appearance of light-scattering globules in the absence and the presence of protease inhibitors including the aminopeptidase inhibitor bestatin. To investigate the effect of the protease inhibitors E-64 and bestatin on the prevention of hyperglycemic cataract, the rat lenses were cultured in medium 199 in the presence of 5.5 and 50 mM glucose and in the absence and the presence of protease inhibitors. Changes in light transmission by the lenses were determined by digital image analysis.
Normal levels of lens fiber cell [Ca(2+)](i), determined by using a cell-permeable dye were approximately 100 nM, and the protease activity determined with BOC-Leu-Met-CMAC was maximum at [Ca(2+)](i) of approximately 500 nM. A large fraction of the FCGAP that cleaves BOC-Leu-Met-CMAC was separated from calpain, which cleaves fluorescein-casein, by diethylaminoethyl (DEAE) gel column chromatography. The FCGAP did not bind to the column, whereas calpain bound to the column and was eluted by approximately 180 mM NaCl. Unlike calpain, the FCGAP did not require calcium for activation and did not cleave fluorescein-casein. However, the Ca(2+)-dependent calpain activated FCGAP, indicating that the latter may exist in pro-protease form. The FCGAP was selectively inhibited by the specific aminopeptidase inhibitor bestatin, indicating that FCGAP could be an aminopeptidase. However, the FCGAP was found to be immunologically distinct from leucine aminopeptidase and calpain. Perfusion of the isolated rat lens fiber cells with Ringer's solution led to their globulization in 30 +/- 3 minutes. Addition of 0.5 mM of the protease inhibitors E-64 and leupeptin increased the globulization time to 60 and 100 minutes, respectively, whereas no globulization of the fiber cells was observed for 4 hours in the presence of 0.05 mM bestatin. In rat lens cultured in medium containing 50 mM glucose, both E-64 and bestatin (0.05 mM each) significantly reduced the extent of opacification, indicating that an aminopeptidase, downstream to a Ca(2+)-dependent protease, may be involved in mediating cataractogenic changes.
In addition to calpain, a Ca(2+)-independent novel protease, FCGAP, a novel aminopeptidase, represents a significant fraction of the total proteolytic activity in the lens. Inhibition of FCGAP by bestatin attenuates Ca(2+)-induced globulization of the isolated fiber cells in vitro and hyperglycemia-induced opacification of cultured rat lens.
The present work is aimed at evaluating the radioprotective effect of curcumin, a naturally occurring phenolic compound on gamma-radiation induced toxicity. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analysed by using cytokinesis blocked micronucleus assay and dicentric aberration (DC). The gamma-radiation at different doses (1, 2 and 4Gy) were found to significantly increase micronuclei (MN), DC frequencies and TBARS level whereas the levels of GSH and antioxidant enzymes were significantly decreased. The maximum damage to lymphocytes was observed at 4Gy irradiation. Curcumin pretreatment (1, 5 and 10microg/ml) significantly decreased the frequency of MN and DC. The levels of TBARS decreased and activities of SOD, CAT and GPx significantly increased along with GSH levels. At 1Gy irradiation all the concentrations of curcumin (1, 5 and 10microg/ml) significantly protected the lymphocytes from radiation damage. At 2Gy irradiation, 5 and 10microg/ml of curcumin showed significant radioprotection. Since the highest damage was observed at 4Gy irradiation both 1 and 5microg/ml of curcumin pretreatment were not sufficient to protect the lymphocytes from radiation damage but 10microg/ml of curcumin significantly protected the cultured lymphocytes from radiation damage. Thus, pretreatment with curcumin gives protection to lymphocytes against gamma-radiation induced cellular damage.
Tardive dyskinesia (TD) is a motor disorder of the orofacial region resulting from chronic neuroleptic treatment. A high incidence and irreversibility of this hyperkinetic disorder has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism related to the pathophysiology of tardive dyskinesia is not completely known. Various animal studies have demonstrated an enhanced oxidative stress and increased glutamatergic transmission as well as inhibition in the glutamate uptake after the chronic administration of haloperidol. The present study investigated the effect of curcumin, an antioxidant, in haloperidol-induced tardive dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypy, locomotor activity, % retention), biochemical (lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase) and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements (VCM's), tongue protrusions, facial jerking in rats which was dose-dependently inhibited by curcumin. Chronic administration of haloperidol also resulted in increased dopamine receptor sensitivity as evident by increased locomotor activity and stereotypy and also decreased % retention time on elevated plus maze paradigm. Pretreatment with curcumin reversed these behavioral changes. Besides, haloperidol also induced oxidative damage in all major regions of brain which was attenuated by curcumin, especially in the subcortical region containing striatum. On chronic administration of haloperidol, there was a decrease in turnover of dopamine, serotonin and norepinephrine in both cortical and subcortical regions which was again dose-dependently reversed by treatment with curcumin. The findings of the present study suggested for the involvement of free radicals in the development of neuroleptic-induced tardive dyskinesia and point to curcumin as a possible therapeutic option to treat this hyperkinetic movement disorder.
Alzheimer's disease (AD) is associated with beta-amyloid accumulation, oxidative stress and mitochondrial dysfunction. However, the effects of genetic mutation of AD on oxidative status and mitochondrial manganese superoxide dismutase (MnSOD) production during neuronal development are unclear. To investigate the consequences of genetic mutation of AD on oxidative damages and production of MnSOD during neuronal development, we used primary neurons from new born wild-type (WT/WT) and amyloid precursor protein (APP) (NLh/NLh) and presenilin 1 (PS1) (P264L) knock-in mice (APP/PS1) which incorporated humanized mutations in the genome. Increasing levels of oxidative damages, including protein carbonyl, 4-hydroxynonenal (4-HNE) and 3-nitrotyrosine (3-NT), were accompanied by a reduction in mitochondrial membrane potential in both developing and mature APP/PS1 neurons compared with WT/WT neurons suggesting mitochondrial dysfunction under oxidative stress. Interestingly, developing APP/PS1 neurons were significantly more resistant to beta-amyloid 1-42 treatment, whereas mature APP/PS1 neurons were more vulnerable than WT/WT neurons of the same age. Consistent with the protective function of MnSOD, developing APP/PS1 neurons have increased MnSOD protein and activity, indicating an adaptive response to oxidative stress in developing neurons. In contrast, mature APP/PS1 neurons exhibited lower MnSOD levels compared with mature WT/WT neurons indicating that mature APP/PS1 neurons lost the adaptive response. Moreover, mature APP/PS1 neurons had more co-localization of MnSOD with nitrotyrosine indicating a greater inhibition of MnSOD by nitrotyrosine. Overexpression of MnSOD or addition of MnTE-2-PyP(5+) (SOD mimetic) protected against beta-amyloid-induced neuronal death and improved mitochondrial respiratory function. Together, the results demonstrate that compensatory induction of MnSOD in response to an early increase in oxidative stress protects developing neurons against beta-amyloid toxicity. However, continuing development of neurons under oxidative damage conditions may suppress the expression of MnSOD and enhance cell death in mature neurons.
Several micronutrients present in fruits and vegetables exhibit anticancer activity as a result of their actions on molecular targets involved in carcinogenesis and tumor progression. Curcumin, a phenolic phytochemical derived from the rhizome of Curcuma longa, exhibits both cancer-preventative activity and growth inhibitory effects on neoplastic cells. Several studies report that curcumin inhibits cancer cell proliferation and induces apoptosis in cancer cells through p21-mediated cell cycle arrest. Cancer cells that are deficient in p21 are also reported to be more prone to undergo apoptosis in response to a variety of cytotoxic agents. In this study, we determined whether curcumin-induced cytotoxicity in cultures of HCT-116 human colon cancer cells was dependent on p21 status. Curcumin killed wild-type HCT-116 cells in a dose- and time-dependent manner, as measured in an MTT cell viability assay. Moreover, an equivalent cytotoxic effect by curcumin was observed in both p21(+/+) and p21(-/-)HCT-116 cells, indicating that curcumin-induced cytotoxicity was p21-independent. Primary cultures of human dermal fibroblasts were less sensitive than HCT-116 colon cancer cells to lower doses of curcumin, suggesting a degree of selectivity for neoplastic cells. Western blot analysis showed that cell death in curcumin-treated cultures of p21(+/+) and p21(-/-) HCT-116 cells was associated with a reduction in pro-caspase-3 and PARP-1 cleavage, which are indicative of apoptosis. We conclude that curcumin-induced apoptosis in HCT-116 colon cancer cells does not depend on p21 status.
ZnO nanorod induced apoptosis via p53, survivin and bax/bcl-2 pathways mediated by oxidative stress in human alveolar adenocarcinoma cells
- M Ahamed
- M J Akhtar
- M Raja
- I Ahmad
- M K J Siddiqui
- M S Alsalhi
- S A Alrokayan
Ahamed, M., Akhtar, M.J., Raja, M., Ahmad, I., Siddiqui, M.K.J., AlSalhi, M.S.,
Alrokayan, S.A., 2011c. ZnO nanorod induced apoptosis via p53, survivin and
bax/bcl-2 pathways mediated by oxidative stress in human alveolar
adenocarcinoma cells. Nanomedicine: NBM 7, 904-913.
Curcumin attenuates 6
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Evaluation of acute oxidative stress induced by NiO nanoparticles in Vivo and in Vitro Curcumin potentiates doxorubicin-induced apoptosis in H 9 c 2 cardiac muscle cells through generation of reactive oxygen species
- M Horie
- H Fukui
- K Nishio
- S Endoh
- H Kato
- K Fujita
Horie, M., Fukui, H., Nishio, K., Endoh, S., Kato, H., Fujita, K., et al., 2011. Evaluation of acute oxidative stress induced by NiO nanoparticles in Vivo and in Vitro. J. Occup. Health. doi:10.1539/joh.L10121. Hosseinzadeh, L., Behravan, J., Mosaffa, F., Bahrami, G., Bahrami, A., Karimi, G., 2011. Curcumin potentiates doxorubicin-induced apoptosis in H 9 c 2 cardiac muscle cells through generation of reactive oxygen species. Food Chem. Toxicol. 49, 1102–1109.
A simple quantitative procedure using Microsomal lipid peroxidation
- E Borenfreund
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