Article

Ultrahigh reactivity provokes nanotoxicity: Explanation of oral toxicity of nano-copper particles

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  • changqing oilfield company
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Abstract

Recently, studies on the biological effects of nanomaterials show signs that some of the manufactured nanoparticles exhibit unexpected toxicity to living organisms. It has previously been reported that the copper particles possess size-depended toxicity. In this paper, we propose that the ultrahigh chemical reactivity of nano-copper results in the specific nanotoxicity which is fully proved by in vitro and in vivo experiment. Using chemical kinetics study (in vitro) and blood gas and plasma electrolytes analysis (in vivo), we found that high reactivity cause the big toxicological difference between small size (23.5 nm) and big size (17 microm). The result is also consistent with biochemistry assay, pathological examination and copper content measurement in renal tissue in vivo. For chemical reactive nanoparticles, metallic nano-copper for instance, both the particles themselves and the resulting product (copper ion) should be fully explored. The nano-copper particles may not compromise the mice directly, however, they lead to the accumulation of excessive alkalescent substance and heavy metal ions (copper ions) culminating the metabolic alkalosis and copper ion overload.

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... of copper under the current evaluation. 29 30 Adequate information on various aspects both for the nanomaterial characterisation and the 31 toxicological evaluation including experiment performance and experimental data obtained 32 ...
... ( should be explored (Meng et al., 2007). 30 No information on long-term repeated dose toxicity of Cu-NPs is available. ...
... ( should be explored (Meng et al., 2007). 30 No information on long-term repeated dose toxicity of Cu-NPs is available. 31 32 In conclusion, oral exposure to Cu NPs may induce systemic toxicity depending on the dose, 33 and part of that toxicity maybe due to release of Cu ions. ...
Book
"SCCS OPINION ON Copper (nano) and Colloidal Copper (nano)" SCCS/1621/20 - Preliminary Opinion U. Bernauer, L. Bodin, Q. Chaudhry, P.J. Coenraads, M. Dusinska, E. Gaffet, E. Panteri, C. Rousselle, M. Stepnik, S. Wijnhoven, W.H. de Jong, N. von Götz The SCCS adopted this document at its plenary meeting on on 27-28 October 2020 (49 Pages) On line 9 November 2020 https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_245.pdf Conclusion of the opinion: 1. In view of the above, and taking into account the scientific data provided, does the SCCS consider the nanomaterials Copper and Colloidal Copper safe when used in leave-on and rinse-off dermal and oral cosmetic products including: skin, nail and cuticle, hair and scalp and oral hygiene products, at a maximum concentration of 1 % (for both Copper and Colloidal Copper) and with specifications as reported in the attached list, taking into account reasonably foreseeable exposure conditions? The SCCS has considered all the information provided by the Notifiers and is of the opinion that it is not possible to carry out safety assessment of the nanomaterials Copper and Colloidal Copper due to the limited or missing essential information. Much of the information provided on toxicity relates to copper as such, and in the absence of full study reports, it is not possible to determine the relevance of the data for nano-forms of copper under the current evaluation. Adequate information on various aspects both for the nanomaterial characterisation and the toxicological evaluation including experiment performance and experimental data obtained need to be provided (as summarised in Annex I). 2. Does the SCCS have any further scientific concerns with regard to the use of Copper and Colloidal Copper in nano form in cosmetic products? The information provided by the Notifiers, and obtained from scientific literature, suggests possible systemic uptake of Cu nanoparticle (and/or ionic Cu), which may lead to accumulation in certain organs - notably the liver and spleen. In addition, the available literature data indicate potential mutagenic/genotoxic and immunotoxic/nephrotoxic effects of copper nanomaterials. These indications raise an alert that warrants further safety evaluation of copper nanomaterials used as cosmetic ingredients. The SCCS concerns for consumer safety in this regard are detailed in Annex II. Annex I provides an overview of the information provided by the Notifiers compared to the data requirements as given in the SCCS checklists for Applicants submitting dossiers on Cosmetic Ingredients to be evaluated by the SCCS (SCCS/1588/17). Keywords: SCCS, scientific opinion, Copper (nano), Colloidal Copper (nano), CAS No 7440-50-8, EC No. 231-159-6, Regulation 1223/2009 Opinion to be cited as: SCCS (Scientific Committee on Consumer Safety), Opinion on Copper (nano) and Colloidal Copper (nano), 27-28 October 2020, SCCS/1621/2020.
... of copper under the current evaluation. 29 30 Adequate information on various aspects both for the nanomaterial characterisation and the 31 toxicological evaluation including experiment performance and experimental data obtained 32 ...
... ( should be explored (Meng et al., 2007). 30 No information on long-term repeated dose toxicity of Cu-NPs is available. ...
... ( should be explored (Meng et al., 2007). 30 No information on long-term repeated dose toxicity of Cu-NPs is available. 31 32 In conclusion, oral exposure to Cu NPs may induce systemic toxicity depending on the dose, 33 and part of that toxicity maybe due to release of Cu ions. ...
... Since the interaction between nanomaterials and living organisms is a function of not only the size of nanoparticles but also their form, it is extremely important to discriminate the biodistribution of particles with different scales and state. We reported the biological fate of three types of copper composites, including nano-CuO (23.5 nm), micro-CuO (17 μm) and copper ions, in male ICR mice by oral gavage at a dose of 70 mg kg -1 body weight (Meng et al., 2007). The copper concentrations in the nano-CuO and copper ion groups were much higher than the micro-CuO group. ...
... Intriguingly, in spite of a marked GNC retention in the kidney after 28 days, the renal tissue almost completely recovered, indicating that the clearance of nanoparticles is the main process leading to renal injury. Unlike inert gold nanoparticles, copper oxide nanoparticles (23.5 nm) not only accumulate in the kidney, but also affect renal metabolic activity by interacting with gastric acid, thus resulting in nephrotoxicity (Meng et al., 2007). The retained nano CuO can continuously release heavy metal ions through reacting with gastric acid. ...
Article
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Due to their many advantageous properties, nanomaterials (NMs) have been utilized in diverse consumer goods, industrial products, and for therapeutic purposes. This situation leads to a constant risk of exposure and uptake by the human body, which are highly dependent on nanomaterial size. Consequently, an improved understanding of the interactions between different sizes of nanomaterials and biological systems is needed to design safer and more clinically relevant nano systems. We discuss the sizedependent effects of nanomaterials in living organisms. Upon entry into biological systems, nanomaterials can translocate biological barriers, distribute to various tissues and elicit different toxic effects on organs, based on their size and location. The association of nanomaterial size with physiological structures within organs determines the site of accumulation of nanoparticles. In general, nanomaterials smaller than 20 nm tend to accumulate in the kidney while nanomaterials between 20 and 100 nm preferentially deposit in the liver. After accumulating in organs, nanomaterials can induce inflammation, damage structural integrity and ultimately result in organ dysfunction, which helps better understand the size-dependent dynamic processes and toxicity of nanomaterials in organisms. The enhanced permeability and retention effect of nanomaterials and the utility of this phenomenon in tumor therapy are also highlighted.
... Several in vitro studies have been conducted. However, only a few studies reported the in vivo toxicity of copper nanoparticles [138][139][140][141]. No information was provided on the bioavailability and excretion data of long-term exposure to copper nanoparticles. ...
... Future research is needed to provide a detailed and systematic overview of both the in vitro and the in vivo toxicity of copper nanoparticles, as well as their kinetics. Recently, the preliminary investigation of the biocompatibility of copper nanoparticles showed that they have toxicity in both humans and the environment [141,142]. Even though copper is sustained in the homeostasis of the human body, excess copper showed toxic effects on the kidney and liver [142,143]. ...
Article
Full-text available
Nanoparticles based on metal and metallic oxides have become a novel trend for dental applications. Metal nanoparticles are commonly used in dentistry for their exclusive shape-dependent properties, including their variable nano-sizes and forms, unique distribution, and large surface-area-to-volume ratio. These properties enhance the bio-physio-chemical functionalization, antimicrobial activity, and biocompatibility of the nanoparticles. Copper is an earth-abundant inexpensive metal, and its nanoparticle synthesis is cost effective. Copper nanoparticles readily intermix and bind with other metals, ceramics, and polymers, and they exhibit physiochemical stability in the compounds. Hence, copper nanoparticles are among the commonly used metal nanoparticles in dentistry. Copper nanoparticles have been used to enhance the physical and chemical properties of various dental materials, such as dental amalgam, restorative cements, adhesives, resins, endodontic-irrigation solutions, obturation materials, dental implants, and orthodontic archwires and brackets. The objective of this review is to provide an overview of copper nanoparticles and their applications in dentistry.
... 15 These detrimental effects of CuO-NPs occurred due to the nanoparticles can be absorbed across the gastrointestinal tract, and pass through the mesentery lymph supply and lymph node to liver and spleen; where reticuloendothelial system can accumulate copper from blood by phagocytosis, predominantly NPs, which have not been completely dissolved. 61,62 The accumulated NPs led to Figure 6 Photomicrographs of mice splenic tissues. Rats were treated as Figure 2. Spleen tissues of control mice (A) showed normal histological structure. ...
... This might be attributed to the size of NPs as the biologically synthesized CuO-NPs had smaller, spherical shaped particles while chemically synthesized CuO-NPs had a larger size range and spherical or elongated particles. Previous studies 61,65 demonstrated that the in vivo toxic effects of nanocopper particles were more prominent than microcopper particles depending on mass basis, huge specific surface area and high solubility in physiological milieus of Cu-NPs when administered orally. Mortimer et al 66 quantifed the size-dependent toxic impact of CuO-NPs and indicated that they were 10 to 20 times more toxic than its bulk form. ...
Article
Full-text available
Introduction: Copper oxide nanoparticles (CuO-NPs) are widely used as feed additives for livestock and poultry and implicated in many biomedical applications; however, overload of copper NPs induces various toxicological changes and dysfunction of animal's organs. Thus, this study was designed to evaluate the comparative toxicological effects of biologically and chemically synthesized CuO-NPs on mice. Methods: Transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to characterize the sizes, shapes and functional groups of CuO-NPs. Forty-five mice were randomly allocated into three groups. Control group received distilled water. The second group was administered a single dose of biologically synthesized CuO-NPs (500 mg/kg bw) orally. The third group was administered a single dose of chemically synthesized CuO-NPs (500 mg/kg bw) orally. Results: TEM revealed that biologically synthesized NPs were spherical in shape, whereas chemically synthesized NPs were spherical or elongated in shape. XRD showed that the size of biologically synthesized NPs ranged from 4.14 to 12.82 nm and that of chemically synthesized NPs ranged from 4.06 to 26.82 nm. FT-IR spectroscopy indicated that the peaks appeared between 779 cm-1 and 425 cm-1 in biologically synthesized NPs and between 858 cm-1 and 524 cm-1 in chemically synthesized NPs were for Cu-O nanostructure. Four mice died due to administration of biologically synthesized CuO-NPs. Both biologically and chemically synthesized CuO-NPs induced leukocytosis, elevated serum activities of alanine aminotransferase and aspartate aminotransferase and serum levels of urea and creatinine and increased P53 mRNA and caspase-3 protein expressions in hepatic tissues. Moreover, CuO-NPs induced degenerative and necrotized changes in hepatic, renal and splenic tissues. Biochemical, apoptotic and pathological changes were more serious in mice administered with biologically synthesized CuO-NPs. Conclusion: This study indicated that a high dose of biologically and chemically synthesized CuO-NPs induced adverse effects on hepatic, renal and splenic tissues. At the same dose level, the biologically synthesized CuO-NPs evoked more potent toxic effects than the chemically synthesized CuO-NPs.
... Chen et al. observed that the exposure of rats to zerovalent copper nanoparticles (ZVCN) causes severe impairment of the kidneys, liver, and spleen of these animals [290]. Meng et al. observed metabolic alkalosis and the accumulation of copper in the kidneys and mice exposed to ZVCN [291]. Lei et al. evaluated the biochemical composition of urine, serum, and extracts of liver and kidney tissues from rats treated with different doses of CuNPs for 5 days [292]. ...
... In serum, the levels of lactate, 3hydroxybutyrate, acetate, creatine, triglycerides, and phosphatides were higher than normal, and glucose levels were lower than normal. These changes are associated with the death of mitochondria and lipid β-oxidation [290][291][292]. ...
Article
Nanotechnology is a cutting-edge area with numerous industrial applications. Nanoparticles are structures that have dimensions ranging from 1–100 nm which exhibit significantly different mechanical, optical, electrical, and chemical properties when compared with their larger counterparts. Synthetic routes that use natural sources, such as plant extracts, honey, and microorganisms are environmentally friendly and low-cost methods that can be used to obtain nanoparticles. These methods of synthesis generate products that are more stable and less toxic than those obtained using conventional methods. Nanoparticles formed by titanium dioxide, zinc oxide, silver, gold, and copper, as well as cellulose nanocrystals are among the nanostructures obtained by green synthesis that have shown interesting applications in several technological industries. Several analytical techniques have also been used to analyze the size, morphology, hydrodynamics, diameter, and chemical functional groups involved in the stabilization of the nanoparticles as well as to quantify and evaluate their formation. Despite their pharmaceutical, biotechnological, cosmetic, and food applications, studies have detected their harmful effects on human health and the environment; and thus, caution must be taken in uses involving living organisms. The present review aims to present an overview of the applications, the structural properties, and the green synthesis methods that are used to obtain nanoparticles, and special attention is given to those obtained from metal ions. The review also presents the analytical methods used to analyze, quantify, and characterize these nanostructures.
... They enter in the cells of the organ and remain there for an unknown duration before getting excreted or leaving to other organs (Fischer and Chan, 2007). Interaction with biological systems can give rise to toxic effects like allergy (Maynard et al., 2006), tissue and DNA damage (Nel et al., 2006), ROS generation (Meng et al., 2007), fibrosis, deposition in different organs that can lead to organ failure, inflammation and cytotoxicity (Singh et al., 2009). Nanomaterials may change the mineral concentration beyond the alarming limits. ...
... They enter in the cells of the organ and remain there for an unknown duration before getting excreted or leaving to other organs (Fischer and Chan, 2007). Interaction with biological systems can give rise to toxic effects like allergy (Maynard et al., 2006), tissue and DNA damage (Nel et al., 2006), ROS generation (Meng et al., 2007), fibrosis, deposition in different organs that can lead to organ failure, inflammation and cytotoxicity (Singh et al., 2009). Nanomaterials may change the mineral concentration beyond the alarming limits. ...
Article
Full-text available
Nanomaterials can be composed of many different base materials (carbon, silicon, and metals such as gold, cadmium, aluminium and selenium). Generally the nano-particles are part of volcanic eruptions, forest fires, fumes generated during welding, metal smelting, automobile exhaust and other industrial processes. The present study was conducted to understand the effects of nano alumina as cell mediated immune response on forty White leghorn chickens of two week age. The chickens were randomly divided into two groups control (Group I) and treated (Group II). The control group was fed with normal standard recommended feed while treated group exposed to nano alumina through oral route in feed for three months. RO water was provided to both the groups.The cell mediated immune response was seen at the end of experiment, taking random samples from ten birds from each group. The results in this study revealed that delta optical density of LST (Lymphocyte Stimulation Test) values showed no significant change while the mean values of treated group was 18.29 % increased as compared to control group at 90th days post treatment.
... Nanomaterials enter the cells of the organ and reside in the cells for an unknown amount of time before moving to other organs or before getting excreted (Fischer and Chan, 2007) [6] . Interaction with biological systems can give rise to toxic effects like allergy (Maynard et al., 2006) [15] , fibrosis, deposition in different organs that can lead to organ failure, inflammation, cytotoxicity (Nel et al., 2006) [20] , ROS generation (Meng et al., 2007) [16] , tissue damage and DNA damage (Singh et al., 2009) [27] . Interaction of nanoparticles with lymphocytes and other cell types can grant to a varied spectrum of possible impacts, including inflammation, hypersensitivity and immunomodulation (Ambwani et al., 2015) [1] . ...
... Nanomaterials enter the cells of the organ and reside in the cells for an unknown amount of time before moving to other organs or before getting excreted (Fischer and Chan, 2007) [6] . Interaction with biological systems can give rise to toxic effects like allergy (Maynard et al., 2006) [15] , fibrosis, deposition in different organs that can lead to organ failure, inflammation, cytotoxicity (Nel et al., 2006) [20] , ROS generation (Meng et al., 2007) [16] , tissue damage and DNA damage (Singh et al., 2009) [27] . Interaction of nanoparticles with lymphocytes and other cell types can grant to a varied spectrum of possible impacts, including inflammation, hypersensitivity and immunomodulation (Ambwani et al., 2015) [1] . ...
Article
Full-text available
Present study was conducted to understand the affects of nano alumina on different clinical signs and growth parameters in White leghorn chickens. The randomly divided control group was fed with normal standard recommended feed while treated group exposed to nano alumina through oral route in feed for three months. The birds of control group (group I) showed signs of some increased activeness or aggressiveness. At the time of feeding birds from treated group (group II) showed increased response for feeding as compare to group I. There was increased fighting tendency noticed in birds of group II. There was no significant difference in body weight observed between group I and group II throughout the experiment at different time intervals. There was a slight 0.33 %, non significant decrease in the body weight of treated group as compared to controls at 90 days post treatment (DPT).
... Histological examination indicates that CuONPs were extremely toxic to the kidney and liver structure for M. musculus (Meng et al, 2007;Melegari et al, 2013;Ognik et al, 2017), in spite of the short duration of exposure and low applied doses of CuONPs. In liver tissue damage of hepatocytes can be observed, in addition to hemorrhaging in hepatic tissues, expansion of sinusoid space, at dose 100 mg/kg can be seen congestion of the central vein associated with red blood cells infiltration leading to hepatocytes rupture as a final result, it is noticeable that these effects increase by increasing the dose of the CuONPs, kidney tissue revealed damage in renal capsule, enlargement in glomerulus, loses in urinary space associated with vacuolization in cytoplasm, these acute toxic effects of CuONPs convert the normal structure of both liver and kidney tissue of M. musculus, causes severe alterations most of them are irreversible, these results agreed with study of Miron and Mahbubeh (2014). ...
Article
Full-text available
The current study was conducted to investigate the histopathological and toxic effects of Copper oxide nanoparticles (CuONPs), which were synthesized by using Q-switched pulsed Nd: YAG laser ablation. CuONPs were synthesized by using Q-switched pulsed Nd: YAG laser ablation of a pure copper sheet submerged in aqueous media, their toxicity was studied on the albino mice Mus musculus by oral administration for twenty male albino mice that divided into four groups (5 male per cage). Four different doses of CuONPs (0, 25, 50 and 100) mg\kg were used. The animals were given the CuONPs once a day for one week, while the control group exposed to Distilled Water (DW). The acute toxicity was investigated by Histopathological changes for both liver and kidney of exposed animals beside genotoxic effects by investigation bone marrow cells' mitotic index (MI) and total chromosomal aberration (TCA). From findings the histological analyses refer to real histopath in liver in all doses, hepatocytes rupture, and dilated blood sinusoids in high dose (100) mg/kg accumulation of chronic inflammatory cells were noticed, while kidney tissue suffered from renal capsule damage, enlargement in glomerulus, loses in urinary space associated with cytoplasmic vacuolization. Cytogenetic parameters affected by this treated by a reduction in proliferative bone marrow index and elevation total chromosomal abnormalities. CuONPs not completely safe and has toxicity on internal organs of exposed mice also cytogenetic parameters showed significant cytotoxic effects on bone marrow cells of mice by reduction of Mitotic index (MI), and induced structural chromosomal changes.
... Also spleen toxicity accompanied by immunotoxicity was observed for Cu-NPs after 28 days intragastric administration to rats (Zhou et al. 2019). For toxic effects on the kidney, the toxicity might be attributed to the relatively high chemical reactivity of small size (23.5 nm) Cu NPs compared to big size (17 micron) particles, suggesting that both the toxicity of the particles and the resulting ions should be explored (Meng et al., 2007). No information on long-term repeated dose toxicity of Cu-NPs is available. ...
Book
The SCCS adopted this document by written procedure on 5 March 2021 (49 Pages) Mise en ligne le 5 Mars 2021 https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs_o_245.pdf
... [10][11][12][13] Small size is reported to be one of the reasons for the cytotoxic effects of nanoparticles. 7,[14][15][16] The cytotoxicity of CuNPs mainly comes from their ability to generate reactive oxygen species (ROS), 17,18 which induce cell death. Previous studies have mainly focused on the cytotoxicity of CuNPs in the liver, 19 kidney, 20 and spleen. ...
Article
Full-text available
Purpose: The toxicity of copper nanoparticle (CuNP) exposure in the ovaries has attracted attention recently, but the precise molecular mechanism involved requires further investigation. We investigated the cytotoxicity of CuNPs in ovarian granulosa cells and the protective effect of heme oxygenase 1 (HO-1) against CuNP-induced damage. Methods: Human ovarian granulosa cells (COV434) were treated with CuNPs, and cytotoxicity was evaluated using Cell Counting Kit-8 and flow cytometry assays. Oxidative stress was identified using biochemical markers of oxidation and anti-oxidation. The protein levels of mitogen-activated protein kinase 14 (MAPK14), phospho-MAPK14, nuclear factor erythroid 2-related factor 2 (Nrf2), and HO-1 were measured by immunoblotting. Subsequently, for oxidative stress parameter detection, the cells were pre-treated with hemin to induce HO-1 expression prior to CuNP treatment. Results: Exposure to CuNPs decreased cell viability and the mitochondrial membrane potential, increased the apoptosis rate, and induced oxidative stress. Furthermore, hemin pretreatment induced HO-1 expression in cells, which partially reduced the accumulation of reactive oxygen species induced by CuNPs and increased the levels of antioxidant enzymes. Conclusion: CuNPs exert cytotoxic effects on human ovarian granulosa cells by inducing oxidative stress, and may induce HO-1 expression via the MAPK14-Nrf2 signaling pathway. Moreover, HO-1 protects against oxidative stress induced by CuNPs.
... Moreover, as a result of their small size, NMs have the ability to penetrate cells and organelles. Several studies have also shown an increase in intracellular oxidative stress and damage when cells are exposed to NMs such as carbon nanotubes (Francis and Devasena, 2018), gold nanoparticles , copper nanoparticles (Meng et al., 2007), titanium NMs (Demir, 2020), etc. These events often lead to adverse effects such as DNA aberration, genetic instability and inflammation depending upon the cell type, nature of NM and material concentration (Demir, 2021). ...
Article
Full-text available
Immunotherapy holds great promise in overcoming the limitations of conventional regimens for cancer therapeutics. There is growing interest among researchers and clinicians to develop novel immune-strategies for cancer diagnosis and treatment with better specificity and lesser adversity. Immunomodulation-based cancer therapies are rapidly emerging as an alternative approach that employs the host’s own defense mechanisms to recognize and selectively eliminate cancerous cells. Recent advances in nanotechnology have pioneered a revolution in the field of cancer therapy. Several nanomaterials (NMs) have been utilized to surmount the challenges of conventional anti-cancer treatments like cytotoxic chemotherapy, radiation, and surgery. NMs offer a plethora of exceptional features such as a large surface area to volume ratio, effective loading, and controlled release of active drugs, tunable dimensions, and high stability. Moreover, they also possess the inherent property of interacting with living cells and altering the immune responses. However, the interaction between NMs and the immune system can give rise to unanticipated adverse reactions such as inflammation, necrosis, and hypersensitivity. Therefore, to ensure a successful and safe clinical application of immunomodulatory nanomaterials, it is imperative to acquire in-depth knowledge and a clear understanding of the complex nature of the interactions between NMs and the immune system. This review is aimed at providing an overview of the recent developments, achievements, and challenges in the application of immunomodulatory nanomaterials (iNMs) for cancer therapeutics with a focus on elucidating the mechanisms involved in the interplay between NMs and the host’s immune system.
... Highest dose caused massive necrobiosis [53]. Contrariliy, a low dose (70 mg/kg) also caused glomerulonephritis and renal tubular necrosis in the same animal model [54]. This study suggested greater renal toxicity of CuNPs at a lower dose than higher dose. ...
... Copper nanomaterials have been documented to possess toxic effects on the liver and kidney. Nano-copper has resulted severe impairment in liver, kidney, and spleen in experimental animals after oral administration and interacting with gastric juice [10]. Silver NPs have been detected in various organs, including lungs, spleen, kidney, liver, and brain after exposing the rats to silver nanoparticles either via inhalation or by subcutaneous injection [11]. ...
... They think that nanocopper may play a role by reacting copper (Cu) ions and Cu particles in low-pH gastric juice. But, some scholars found that nano-copper can damage mitochondrial function and enhance ketone formation, fatty acid β oxidation, and glycolysis process [6][7][8]. Furthermore, it can damage the liver, kidney, spleen, and nervous system [9,10] and bring potential negative effects on human health and the ecosystem [11]. ...
Article
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The Wumeng semi-fine wool sheep is vital to the production system of the Wumeng mountainous area in Southwest China. To study the effect of nano-copper poisoning in the Wumeng semi-fine wool sheep, nano-copper poisoning model was established in sheep. We determined blood physiological and biochemical parameters, immune indexes, and antioxidant indicators. The results showed that Hb, RBC, and PCV levels in blood from the nano-copper group were markedly lower (P < 0.01) than those in the control group. Serum LDH, AST, ALT, CPK, and Cp from the nano-copper group were significantly higher (P < 0.01) than those in control animals. Serum SOD, GSH-Px, CAT, and T-AOC from the nano-copper group were significantly lower (P < 0.01) than those in control sheep, and MDA content in serum from the nano-copper group were markedly higher (P < 0.01) than those in control sheep. The levels of IL-2, IL-6, IL-1β, IgA, IgM, and IgG from the nano-copper group were significantly lower (P < 0.01) than those in the control group. It was concluded that nano-copper poisoning could not only affect the immune function of Wumeng semi-fine wool sheep but also reduce the antioxidant capacity.
... During the process of nanoparticle formation, the pH of the solution greatly influences the size of nanoparticles. The Cu-NP showed higher solubility and zeta potential when prepared under acidic (pH 5.5) conditions [31,32]. At higher pH levels, Cu oxide nanoparticles are formed instead of Cu-NP due to the presence of sodium hydroxide in excess, and a further increase in pH forms Cu hydroxide without any Cu-NP formation [33]. ...
Article
Full-text available
Copper (Cu) is a vital trace mineral involved in many physiological functions of the body. In the poultry industry, copper sulfate is being used as a major source of Cu. Copper in the bulk form is less available in the body, and much of its amount excreted out with feces causing environmental pollution and economic loss. The application of nanotechnology offers promise to address these issues by making nanoparticles. Copper nanoparticles (Cu-NP) are relatively more bioavailable due to their small size and high surface to volume ratio. Although, there is limited research on the use of Cu-NP in the poultry industry. Some researchers have pointed out the importance of Cu-NP as an effective alternative of chemical, anti-bacterial agents, and growth promoters. The effect of Cu-NP depends on their size, dose rate and the synthesis method. Apart from there, high bioavailability Cu-NP exhibited positive effects on the immunity of the birds. However, some toxic effects of Cu-NP have also been reported. Further investigations are essentially required to provide mechanistic insights into the role of Cu-NP in the avian physiology and their toxicological properties. This review aims to highlight the potential effects of Cu-NP on growth, immune system, antioxidant status, nutrient digestibility, and feed conversion ratio in poultry. Moreover, we have also discussed the future implications of Cu-NP as a growth promoter and alternative anti-bacterial agents in the poultry industry.
... Only few reports describe the toxicity vs. exposure time of NPs, and data are inconsistent with our results on CDs. For example, toxicity of metallic NPs was shown to be a relatively long process as it involves dissolution of the NPs inside the cell and release of toxic ions (Meng et al., 2007). Toxic effects of CuO and ZnO NPs were thus observed after 24 hours exposure (Kim et al., 2017). ...
Thesis
Carbon dots (CDs) are the latest member of the family of carbon nanoparticles (NPs) to be discovered. They were isolated for the first time in 2004, during electrophoresis purification of carbon nanotubes. In addition to their nanometric size, these objects are almost spherical and hydrophilic, and are generally presented as biocompatible and very weakly toxic NPs. They are fairly easily accessible by synthesis and can be conveniently modified by reaction of the functional groups present on their surface (amines, carboxylic acids, alcohols, etc.). Finally, they exhibit intrinsic fluorescence properties, are relatively resistant to photobleaching, and can be excited by multi-photon irradiation. Thus, like the other members of the family of carbon NPs (graphene, nanodiamonds, fullerenes, nanotubes), CDs have remarkable properties which are the subject of intense research for applications in fields as different as those of electronics, catalysis, energy storage, imaging, and medicine. In the latter area, CDs can find applications as drug delivery systems, like other NPs successfully developed in this field. The work developed during this thesis had two distinct objectives. The first one was to identify the intrinsic physicochemical properties responsible for the toxicity of NPs. For this, the toxicological profile of a large collection of CDs produced in the laboratory and exhibiting various size, charge, and surface chemistry was characterized using in vitro lung models and mice. We found that although the size of the NPs plays an important role it is not, by itself, a predictive element of the toxicity of the NPs. The charge and the surface chemistry largely effect the interactions between the NPs and the biological medium systems and, therefore, their intrinsic toxicity. The second objective of this thesis was to assess the potential of CDs in the field of drug delivery as synthetic gene carriers. We were able to show the superiority of NPs prepared from citric acid and bPEI600 over all other cationic CDs produced in the laboratory. A systematic evaluation has allowed us, step by step, to improve the efficiency of these transfection agents, to exceed that of bPEI25k, a gold standard for in vitro transfection, without significant toxicity. Overall, this work opens up new horizons in NPs research that may provide 1-a better understanding of the toxicological mechanisms of NPs, especially their determinants, and 2-identification of the relationship between the CDs synthesis methods and the efficiency of these NPs as DNA transfection reagents.
... Recently a number of articles have described in vivo metabolism of NPs (Wang et al. 2013a;Feliu et al. 2016). The physiological conditions in the cell compartment (acidic environment in endosomes) or organ (the acidic environment in the stomach, Meng et al. 2007) and the degradation by enzymatic catalysis in cell lysosomes may play primary roles in the metabolism of NPs. The major route for the entrance of nanoparticle into the cells is endocytosis. ...
Chapter
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Nanoparticles (NPs) have found applications in large number of fields which increases the exposure of human to NPs. The potential toxicity of the NPs during the earlier days was not in focus, but during the last decade, much attention has been paid to the potential risk of NP toxicity to human health. In this chapter we summarized biokinetics of NPs and the toxicity of NPs to specific organ systems of the body and different methods used to assess the nanotoxicity using in vivo models. The physicochemical properties of NPs affect their biokinetics and thus toxicity to different organ systems in the body. Cationic NPs enhance their cellular uptake compared to neutral or anionic NPs. NPs are absorbed through different routes and are distributed locally or to distant organs by hematopoietic system. NPs may cross the different barriers in the body and cause toxic effects in different organs and even to the developing embryo. NPs smaller than 5 nm can cross the placental barrier and are highly toxic to the developing embryo. NPs of size more than 80 nm are accumulated in different organs and are rarely excreted in feces or urine. Accumulation of the NPs may disturb the homeostasis and result in the toxicity to different levels. NPs are more toxic to the lung, brain, intestine, stomach, and developing embryo. Si and TiO2 NP absorption through placenta may lead to 20–30% reduction in uterine weight in pregnant mice. On the other hand, NPs are relatively nontoxic to the kidney. Thus it becomes even more important to assess the toxicity of the NPs in different physiological systems. To assess the toxicity of the NPs, in vivo models are best choice as they mimic the biological system and thus their results are more reliable. Furthermore, proper techniques are also required to assess the toxicity of the NPs for particular organ system. Complete study of the toxicity potential of the NPs should be assessed as this will support the safe application of NPs.
... Nano-copper (Nano-Cu) is a common artificial material, which has been widely used in the production of intrauterine devices, anti-osteoporosis, anti-aging nano-drugs, lubricant additives, high-efficiency catalysts, and animal feed additives, bringing technological revolution to the development of medicine, industry, and animal husbandry [5][6][7][8][9][10]. Nano-Cu has the advantages of small particle size and large specific surface area. ...
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Guizhou black goats are essential to the production system in the Wumeng prairie in the Western China. This study aimed to determine the influence of nano-copper on antioxidant system in copper-deprived Guizhou black goats. We analyzed mineral contents in soil, forage, and goats’ tissues. Blood parameters were also determined. The results showed that copper concentrations in soil and forage were significantly lower, and the iron content was significantly higher in affected compared with healthy area (P < 0.01). Copper concentrations in animal tissues (blood, liver, and hair) were significantly lower and iron content was significantly higher in affected compared with healthy goats (P < 0.01). After supplementation of nano-copper or copper sulfate, copper concentration in blood was significantly increased and iron content was significantly lower (P < 0.01). Compared with nano-copper group, the effect of copper sulfate was slower. Hemoglobin levels, erythrocyte count, and packed cell volume from nano-copper and copper sulfate groups were significantly higher than those in copper-deprived goats (P < 0.01). Compared with the copper-deprived Guizhou black goats, serum ceruloplasmin levels in nano-copper and copper sulfate groups were significantly increased, while serum lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and creatinine were significantly decreased (P < 0.01). Compared with the copper-deprived animals, serum superoxide dismutase, glutathione peroxidase, catalase, and total antioxidant capacity in nano-copper and copper sulfate groups were significantly higher, while serum malondialdehyde content was significantly lower (P < 0.01). The effect of copper sulfate group was significantly lower than that in nano-copper group (P < 0.01). Consequently, nano-copper could not only markedly increase the copper content in blood in copper-deprived Guizhou black goats but also much improves the antioxidant capacity.
... However, many polymeric and inorganic nanomaterials suffer from hostile biologic activity regarding to their potentially toxic by-products. As well medical nanomaterials usual outturns are their adverts biological responses at the materialbody interface so-called nano-toxicology [16][17][18][19]. Therefore, nanomaterials require more functionality to regulate their unfavorable side effects. ...
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Hyphenated electrospinning electrospraying is a versatile method for synthesizing polymeric functional materials with fascinating and tuneable characteristics. In this paper, previously unreported clusters of boron nitride nanotubes (BNNTs) and their hybrid nanofibers with ɛ-polycaprolactone (PCL) were fabricated successfully. For instance, this biocompatible nano fibrous mat may have a potent to encapsulate common anticancer drugs such as doxorubicin (DOX), cisplatin and Fluorouracil (5FU) to minimize their the most lethal side effect, cardiotoxicity, and to improve chemotherapy and manage cardiotoxicity in cancer patients. BNNTs supramolecular solution was prepared with controllable dispersion and agglomeration features. Furthermore, the synthesized PCL nanofibers including BNNTs clusters (PCL/BNNTs) exhibit favourable qualities in the terms of mechanical and thermal strength, hydrophobicity and biocompatibility. Different microscopic and analytical examinations such as: Field emission scanning electron microscopy (FESEM), Furrier transform spectroscopy (FT-IR), Dynamic scanning calorimetry (DSC) and MTT assay were performed. BNNTs clusters were synthesized and then subjected to electrospraying. Simultaneously electrospinning of PCL solution was conducted to provide nanofiber net-like film consisting of BNNT nano-capsulated beads (∼100 nm to ∼1 µm). PCL/BNNTs nanofibers with average diameters of 350 ± 50 nm were synthesized depended on various electrospinning conditions. The results of cytotoxicity assay on cardiac cell line (H9c2 cells) reveal that prepared BNNTs clusters and PCL/BNNTs nanofibers are more biocompatible rather than isolated BNNTs.
... Aunque dichas nanopartículas resultaron menos 50 toxicas que el cobre ionizado , se ha demostrado que las nanoparticulas de cobre pueden llegar a acumularse en hígado, bazo y riñón, lo cual produce una gran alteración en 5 1 dichos órganos . Además, se ha observado que la administración oral de nanoestructuras de cobre de 50 nm o menos, forma iones que se acumulan en gran medida en 52 riñón . Por lo tanto, depende mucho de la administración y medio en el cual son empleadas dichas nanoestructuras para poder decir que son totalmente seguras. ...
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Identificar los posibles riesgos toxicológicos de las diversas nanopartículas utilizadas en productos de consumo humano, así como también revisar las regulaciones existentes en México y el mundo del uso de dichas nanopartículas en el mercado. Presentamos esta revisión bibliográfica de las diversas regulaciones nacionales e internacionales que refieren el uso de las nanopartículas así como también la revisión de bibliografía científica que señala los pros y contras del uso de las nanoestructuras. Existe evidencia científica de la posible toxicidad del constante uso de las nanopartículas. Sin embargo, la toxicidad esta relacionada al material y concentración. No existe una regulación que hable de forma clara y especifica sobre el uso de la nanotecnología en México. Es importante tomar en cuenta la implicación bioética, ambiental y de posibles reacciones adversas a la salud del uso y manejo de la nanotecnología que se desarrolla para su correcta comercialización.
... The variation in the size of NPs could lead to an alteration in their catalytic properties [16]. Meng et al. [17] detected a metabolic alkalosis and copper accumulation in the kidneys in mice that were orally exposed to CuNPs. ...
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Background: Nanotechnology application has widespread use in many products. Copper nanoparticles (CuNPs) are widely used in industrial applications. The present study was conducted to investigate the effect of the ethanolic saffron extract (ESE) as a natural antioxidant on the hepatotoxicity induced by CuNPs in male mice. Methods: The characterization of CuNPs was determined using ultraviolet-visible absorption spectroscopy, particle size analysis, zeta potential, Fourier-transform infrared spectroscopy, and electron microscope. The effect of saffron on the hepatotoxicity induced by CuNPs in mice was evaluated by evaluating the survival rate of the mice, oxidative stress, antioxidant capacity, DNA evaluation, as well as its effect on the histology and transmission electron microscope of the liver. Results: The results revealed that all parameters were affected in a dose-dependent manner by CuNPs. These effects have been improved when the treatment of CuNPs is combined with ethanolic saffron extract. Conclusions: We can conclude that saffron and its bioactive crocin portion can prevent CuNP-induced oxidative liver damage. This substance should be useful as a new pharmacological tool for oxidative stress prevention.
... Also spleen toxicity accompanied by immunotoxicity was observed for Cu-NPs after 28 days intragastric administration to rats (Zhou et al. 2019). For toxic effects on the kidney, the toxicity might be attributed to the relatively high chemical reactivity of small size (23.5 nm) Cu NPs compared to big size (17 micron) particles, suggesting that both the toxicity of the particles and the resulting ions should be explored (Meng et al., 2007). No information on long-term repeated dose toxicity of Cu-NPs is available. ...
... Numerous substances, such as extracellular polymers, model protein, and natural polysaccharides contribute to the stability of CuO NPs in the environment (Miao et al. 2015). On the other hand, toxicity of copper NPs may result from its reactivity through metabolic alkalosis or intracellular dissolution (Meng et al. 2007). ...
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Nanotechnology, as one of the fastest-growing industries, offers many benefits in various fields. However, properties that contribute to its positive effects, in other context, can cause adverse effects to various organisms, such as amphibians. Identifying possible negative effects on its survival is crucial since amphibians are the most threatened group of vertebrates. In that context, we investigated the influence of both nano and bulk copper on embryonic development of agile frog, Rana dalmatina. The embryos were exposed to various concentrations (0.01 mg/L, 0.075 mg/L, 0.15 mg/L or 0.3 mg/L) of either nano (CuO, declared size 40–80 nm) or bulk form (CuSO4·5H2O) for 16 days. Upon the experiment, tadpoles were measured and weighted, then homogenized and their protein, lipid, and carbohydrates content determined, as well as the activity of LDH. Our results suggest stronger negative influence of nano copper to size and weight of tadpoles, and bulk copper on lipid content, while both had strong negative effect on carbohydrates content, and LDH activity. In addition, our results suggest agile frog to be more susceptible to negative influence of both, nano and bulk copper, than commonly used Xenopus laevis.
... In experimental animals, CuO NPs have caused severe damage in the liver, spleen, and kidneys. Highly reactive ionic copper is generated after oral administration and interaction with gastric fluid, which is then deposited in the kidneys of exposed animals [828]. ...
... Thus, CuO-NP exhibited various toxic and barrier integrity-lowering effects in in vitro intestinal and epithelial cell models [16][17][18][19][20][21][22][23][24][25][26][27][28]. Moreover, toxic effects of CuO-NP on the liver, spleen and kidneys have already been described in mouse models [29][30][31]. In this context, the damaging effects of CuO-NP are due to different mechanisms, which mainly include the triggering of oxidative stress [16,21,[32][33][34][35], damage to the genetic material [33,[36][37][38] and the induction of inflammatory processes [35,[39][40][41]. ...
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Copper oxide nanoparticles (CuO-NP) are increasingly used in consumer-related products, which may result in increased oral ingestion. Digestion of particles can change their physicochemical properties and toxicity. Therefore, our aim was to simulate the gastrointestinal tract using a static in vitro digestion model. Toxic properties of digested and undigested CuO-NP were compared using an epithelial mono-culture (Caco-2) and a mucus-secreting co-culture model (Caco-2/HT29-MTX). Effects on intestinal barrier integrity, permeability, cell viability and apoptosis were analyzed. CuO-NP concentrations of 1, 10 and 100 µg mL−1 were used. Particle characterization by dynamic light scattering and transmission electron microscopy showed similar mean particle sizes before and after digestion, resulting in comparable delivered particle doses in vitro. Only slight effects on barrier integrity and cell viability were detected for 100 µg mL−1 CuO-NP, while the ion control CuCl2 always caused significantly higher adverse effects. The utilized cell models were not significantly different. In summary, undigested and digested CuO-NP show comparable effects on the mono-/co-cultures, which are weaker than those of copper ions. Only in the highest concentration, CuO-NP showed weak effects on barrier integrity and cell viability. Nevertheless, a slightly increased apoptosis rate indicates existing cellular stress, which gives reason for further investigations.
... Doudi and Setorki [46] reported lungs and liver damage involving necrosis of the cells and increase in the fibrous tissues of the lungs. Same has also been reported by others [53][54][55][56]. However, the level of toxicity varied depending on concentration applied, physio morphological characteristics of NPs, gender of the rats, and other conditions (reviewed by Naz et al.16]. ...
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Copper nanoparticles were synthesized using Rhus punjabensis leaf extract and assessed for toxicity in vitro against brine shrimp Leishmania tropica and in vivo against Sprague–Dawley rats. The spherical biofunctionalized nanoparticles showed concentration and time-dependent toxicity during in vitro assays. Biocompatibility assessed against Sprague–Dawley rats at 50 and 100 mg/kg (low and high dose) depicted significant variation only in total bilirubin, alanine transaminase, and alkaline phosphatase in both male and female rats at both dose administration; however, non-significant change was recorded on other parameters. Antioxidative enzymes, total proteins, and nitrites also showed significant variation from control in both genders. Histological study revealed alteration in liver, heart, and lungs of male rats on higher dose administration, while female rats on low-dose administration were found safer. The results show that R. punjabensis-mediated CuO nanoparticles are safe at low dose and its application can be expanded as effectual antimicrobial and anticancer agents for pharmaceutical applications.
... Toxic effects of various nanostructures used in dentistry. Toxicity is dependent on the type of toxicity assay, cell line, and physical/chemical properties, dose, side chain (cationic) and the stabilizer[290][291][292][293] Copper oxide • Toxic effects on the liver, kidney and spleen in experimental animals • Genotoxic and cytotoxic • Cell membrane integrity disturbed • Prompting oxidative stress[294][295][296] Silver • After exposing the rats to these NPs, detected in various organs, including lungs, spleen, kidney, liver, and brain. In human hepatocytes, and embryonic kidney cells alteration in mitochondrial activity • Genotoxicity Store in the liver, spleen, lungs, and brain • Ability to cross BBB • Cell Inflammation, lysis and reduced cell viability reduced • Blood coagulation system impaired Increased toxic effects on immune function, liver, kidney, spleen, myocardium, glucose, and lipids homeostasis in experimental animal Increased malondialdehyde after treating human bronchoalveolar carcinoma cells at a dosage range of 10-100 µg/mLNPs of polymeric materials• Non-toxic, non-immunologic and non-inflammatory • Did not activate neutrophils • However, toxicity towards human-like macrophages after surface coating was observed ...
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Overall perspective of nanotechnology and reinforcement of dental biomaterials by nanoparticles has been reported in the literature. However, the literature regarding the reinforcement of dental biomaterials after incorporating various nanostructures is sparse. The present review addresses current developments of glass ionomer cements (GICs) after incorporating various metallic, polymeric, inorganic and carbon-based nanostructures. In addition, types, applications, and implications of various nanostructures incorporated in GICs are discussed. Most of the attempts by researchers are based on the laboratory-based studies; hence, it warrants long-term clinical trials to aid the development of suitable materials for the load bearing posterior dentition. Nevertheless, a few meaningful conclusions are drawn from this substantial piece of work; they are as follows: (1) most of the nanostructures are likely to enhance the mechanical strength of GICs; (2) certain nanostructures improve the antibacterial activity of GICs against the cariogenic bacteria; (3) clinical translation of these promising outcomes are completely missing, and (4) the nanostructured modified GICs could perform better than their conventional counterparts in the load bearing posterior dentition.
... In experimental animals, CuO NPs have caused severe damage in the liver, spleen, and kidneys. Highly reactive ionic copper is generated after oral administration and interaction with gastric fluid, which is then deposited in the kidneys of exposed animals [828]. ...
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Global overpopulation, industrial expansion, and urbanization have generated massive amounts of wastes. This is considered as a significant worldwide challenge that requires an urgent solution. Additionally, remarkable advances in the field of biomedicine have impacted the entire spectrum of healthcare and medicine. This has paved the way for further refining of the outcomes of biomedical strategies toward early detection and treatment of different diseases. Various nanomaterials (NMs) have been dedicated to different biomedical applications including drug delivery, vaccinations, imaging modalities, and biosensors. However, toxicity is still the main factor restricting their use. NMs recycled from different types of wastes present a pioneering approach to not only avoid hazardous effects on the environment, but to also implement circular economy practices, which are crucial to attain sustainable growth. Moreover, recycled NMs have been utilized as a safe, yet revolutionary alternative with outstanding potential for many biomedical applications. This review focuses on waste recycled NMs, their synthesis, properties, and their potential for multiple biomedical applications with special emphasis on their role in the early detection and control of multiple diseases. Their pivotal therapeutic actions as antimicrobial, anticancer, antioxidant nanodrugs, and vaccines will also be outlined. The ongoing advancements in the design of recycled NMs are expanding their diagnostic and therapeutic roles for diverse biomedical applications in the era of precision medicine.
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Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and bioactivities. In our previous study, nano-Cu was found to hamper fetal development; however, the toxicity of nano-Cu and its effects in placental function have not been elucidated. Therefore, we investigated the toxic effects of nano-Cu using rat placenta. Pregnant Sprague-Dawley rats were orally exposed to different copper sources from the third day of gestation (GD 3) to GD 18. We found that nano-Cu (180 mg/kg) and CuCl2.2 H2O increased the accumulation of copper. Besides, nano-Cu and CuCl2.2 H2O disrupted the placental morphology and induced oxidative stress. Micro-copper (micro-Cu) caused similar toxicity in the placenta, but its effects were weaker than that of nano-Cu and CuCl2.2 H2O. In addition, exposure to nano-Cu (180 mg/kg) and CuCl2.2 H2O induced inflammation in the rat placenta. Furthermore, nano-Cu, micro-Cu, and CuCl2.2 H2O upregulated the expression of the autophagy-related proteins, Beclin-1 and LC3 II/ LC3 I, and downregulated that of p62. Moreover, nano-Cu, micro-Cu, and CuCl2.2 H2O downregulated the protein expression of PI3K, p-AKT/AKT, and p-mTOR/mTOR in rat placentas, whereas the protein expression of p-AMPK/AMPK was upregulated. Taken together, our data indicated that prenatal exposure to nano-Cu induced autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways, which associated with oxidative stress and inflammation in rat placenta.
Chapter
Emergence of nanotechnology field in biomedicine advised researchers to investigate the toxicity of nanosized particles. The interactions between metals and microorganisms are always a subject of interest in the last few decades owing to their possible transfer of stored metals to higher organisms. The toxicological impacts of nanoparticles on microbial metabolism and growth have always been the subject of interest for researchers. Several nanomaterials such as metal and metal oxide nanoparticles and carbon materials were screened for their potential applications in the biomedical field. Even though nanoparticles have widespread applications in the field of biology and medicine, there is a serious impact of nanomaterials on human health and environment. There are nanoparticles with huge toxicity as they can pass through biological membranes affecting the physiology of the cell. Potential hazards of nanoparticles are much more wide and diverse on plants, vertebrates, and invertebrates than microorganisms. Yeast, Saccharomyces cerevisiae, is a prominent and highly informative biological model among all in vitro models to evaluate the toxicity of different nanoparticles. It is also important to evaluate the toxicity of nanoparticles using model organism such as S. cerevisiae for the possible applications in different fields. Toxicological effects of nanoparticles vary depending on the size, chemical nature, and surface chemistry of particles. S. cerevisiae and its gene deletion mutant collections are successfully employed as a model to evaluate nanoparticle toxicity owing to their ability to reveal cellular toxicity and detoxification mechanism of nanoparticles. This will further add valuable information for testing the potential of emerging scope of nanoparticle world.
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The rate of translational effort of nanomedicine requires strategic planning of nanosafety research in order to enable clinical trials and safe use of nanomedicine in patients. Herein, the experiences that have emerged based on the safety data of classic liposomal formulations in the space of oncology are discussed, along with a description of the new challenges that need to be addressed according to the rapid expansion of nanomedicine platform beyond liposomes. It is valuable to consider the combined use of predictive toxicological assessment supported by deliberate investigation on aspects such as absorption, distribution, metabolism, and excretion (ADME) and toxicokinetic profiles, the risk that may be introduced during nanomanufacture, unique nanomaterials properties, and nonobvious nanosafety endpoints, for example. These efforts will allow the generation of investigational new drug‐enabling safety data that can be incorporated into a rational infrastructure for regulatory decision‐making. Since the safety assessment relates to nanomaterials, the investigation should cover the important physicochemical properties of the material that may lead to hazards when the nanomedicine product is utilized in humans. Translational nanomedicine requires strategic planning of nanosafety research in order to catalyze clinical trials and safe use of nanomedicine in patients. The safety information of cancer liposomes is summarized, followed by the toxicological data of emerging nanomedicine. A blueprint is provided to plan and generate investigational new drug‐enabling safety assessment, and the knowledge gap and new research direction are discussed.
Chapter
Nanoscale material (nanomaterials)‐based productions and products have proven tremendous potential benefits. These materials have created new possibilities and platform that could possibly resolve global sustainability issues faced by society. However, these advantages need to be assessed alongside the possible loss to the environment, public health, and safety. The properties of nanomaterials or the processes of producing nanomaterials themselves have imposing deleterious effect on the environment, health, and safety. In addition to that, utilization of nanotechnology needs huge amount of natural resources to bring its state‐of‐art characteristics. Hence, now questions have been raised regarding the sustainability of nanoscale materials and products based on them. The current chapter focuses on highlighting all possible factors that may lead to adverse events with their development and subsequent stages and have negative impact on the environment and health. It also addresses the assessment of all evolving nanotechnologies with information on the numerous tools that may be used for them. The existing regulations for nanomaterials in different countries are highlighted, with specific emphasis on harmonization of guidelines throughout the globe in order to make a unique assessment methodology for toxicity assessment and to minimize the time required for the same.
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Flavonoids have long been known for their healing powers in human ailments, with recent trends seeing these natural bioactive components increasingly extended into nutraceuticals and functional foods. Frequent intake of these compounds through diet arguably becomes a natural remedy for lowering the risk of non-communicable diseases. Hydrophobic flavonoids within the spectrum stand out, owing to their remarkable therapeutic effects including the capability of acting as a complementary approach to conventional therapy for COVID-19, suggested by novel research endeavors. However, various physicochemical aspects (e.g., low aqueous solubility, low permeability, and high oxidation susceptibility), as well as undesirable sensory attributes have hindered the direct incorporation of hydrophobic flavonoids into food matrices. Thus, the demand has risen for encapsulated/protected flavonoids that can maintain their original bioactivity during processing, storage, and gastrointestinal digestion. Taking the importance of these facts into consideration, the purpose of this critical review is to discuss different approaches for the encapsulation/delivery of hydrophobic flavonoids. Additionally, the strengths and weaknesses of delivery systems, recommendations to overcome possible challenges, the incorporation of encapsulated hydrophobic flavonoids into food materials, and the importance of considering toxicity aspects of the corresponding delivery systems have been discussed in detail. The influence of flavonoid systems on the overall physicochemical and organoleptic properties of functional food models has also been addressed, with a particular emphasis on the importance of food safety in this regard.
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Engineered metal nanoparticles (ENPs) are frequently incorporated into aerosolized consumer products, known as nano-enabled products (NEPs). Concern for consumer pulmonary exposures grows as NEPs produce high concentrations of chemically modified ENPs. A significant knowledge gap still exists surrounding NEP aerosol respiratory effects as previous research focuses on pristine/unmodified ENPs. Our research evaluated metal containing aerosols emitted from nano-enabled cosmetics and their induction of oxidative stress and DNA damage, which may contribute to epithelial mesenchymal transitions (EMT) within primary human small airway epithelial cells. We utilized an automated NEP generation system to monitor and gravimetrically collect aerosols from two aerosolized cosmetic lines. Aerosol monitoring data was inputted into modeling software to determine potential inhaled dose and in vitro concentrations. Toxicological profiles of aerosols and comparable pristine ENPs (TiO2 and Fe2O3) were used to assess reactive oxygen species and oxidative stress by fluorescent-based assays. Single-stranded DNA (ssDNA) damage and 8-oxoguanine were detected using the CometChip® assay after 24-hour exposure. Western blots were conducted after 21-day exposure to evaluate modulation of EMT markers. Results indicated aerosols possessed primarily ultrafine particles largely depositing in tracheobronchial lung regions. Significant increases in oxidative stress, ssDNA damage, and 8-oxoguanine were detected post-exposure to aerosols versus pristine ENPs. Western blots revealed statistically significant decreases in E-cadherin and increases in vimentin, fascin, and CD44 for two aerosols, indicating EMT. This work suggests certain prolonged NEP inhalation exposures cause oxidative DNA damage, which may play a role in cellular changes associated with reduced respiratory function and should be of concern.
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The wide application of nanomaterials in consumer and medical products has raised concerns about their potential adverse effects on human health. Thus, more and more biological assessments regarding the toxicity of nanomaterials have been performed. However, the different ways the evaluations were performed, such as the utilized assays, cell lines, and the differences of the produced nanoparticles, make it difficult for scientists to analyze and effectively compare toxicities of nanomaterials. Fortunately, machine learning has emerged as a powerful tool for the prediction of nanotoxicity based on the available data. Among different types of toxicity assessments, nanomaterial cytotoxicity was the focus here because of the high sensitivity of cytotoxicity assessment to different treatments without the need for complicated and time-consuming procedures. In this review, we summarized recent studies that focused on the development of machine learning models for prediction of cytotoxicity of nanomaterials. The goal was to provide insight into predicting potential nanomaterial toxicity and promoting the development of safe nanomaterials.
Chapter
Nanoparticles are being employed in numerous diverse fields of engineering and medicine attributed to their exclusive size and inherent physicochemical characteristics. The increased use of nanoparticles resulted in an unregulated environmental release and human exposures thereby prompting toxicological assessments and hazard analysis mandatory. With high frequency of nanoparticles in the market, incomplete assessments, hazard analysis and categorization remain the toughest job. Interestingly, the physicochemical properties are governing factors not only that determines utility, but also their toxicity. Thus, several attempts are being made to link the hazardous effect of particles with its physicochemical properties thereby reducing the experimental requirements. Moreover, it is mandatory to account mechanism of toxicity, which is still lagging. The present study reviews the physicochemical properties as cues to determine the toxicity of nanoparticles with possible mechanisms detailed.
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Nanotechnology has revolutionized the field of biomedical sciences with smart approaches of imaging and treatment. This transformation has led to the development of a new field named ‘nanomedicine’, which has provided prospects for personalized medicines and offers hope for some rare diseases. In this context, the ability to manipulate various nanomaterials to suit diverse applications is a characteristic feature which has gained popularity. Nevertheless, the toxicity exerted by the nanomaterials has limited their lab-to-bench translations. Moreover, the noxiousness of nanomaterials has paved the emergence of another dedicated field named ‘nanotoxicology’. Therefore, it is essential to control nanomaterials’ toxicity and engineer nanomaterials with smart approaches for selective biomedical actions. Here we review engineered nanomaterials including metal and metal oxide, semiconductor, carbon-based, polymeric, and biological-based nanomaterials, and their potential applications in managing microbes, regenerative medicine, tissue engineering, dentistry, cancer treatment, personalized medications, and neglected rare diseases. We discuss the origin of nanotoxicity and how it is influenced by physicochemical properties of nanomaterials, synthesis methods, routes of administration, nano-bio-interface, and choice of the cell lines employed in the assessment. At the end, we discuss strategies and regulations adopted to mitigate the nanotoxicological concerns with future perspectives.
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Nano-copper has been increasingly employed in various products. In previous studies, we showed that nano-copper caused damage in the rat testis, but it remains unclear whether the toxic reaction can affect the reproductive function. In this study, following 28 d of exposure to nano-copper at a dose of 44, 88, and 175 mg/kg/day, there was a decrease in sperm quality, fructose content, and the secretion of sex hormones. Nano-copper also increased the level of oxidative stress, sperm malformation rate, and induced abnormal structural changes in testicular tissue. Moreover, Nano-copper upregulated the expression of apoptosis-related protein Bax and autophagy-related protein Beclin, and downregulated the expression of Bcl2 and p62. Furthermore, nano-copper (175 mg/kg) downregulated the protein expression of AMPK, p-AKT, mTOR, p-mTOR, p-4E-BP1, p70S6K, and p-p70S6K, and upregulated the protein expression of p-AMPK. Therefore, nano-copper induced damage in testicular tissues and spermatogenesis is highly related to cell apoptosis and autophagy by regulating the Akt/mTOR signaling pathway. In summary, excess exposure to nano-copper may induce testicular apoptosis and autophagy through AKT/mTOR signaling pathways, and damage the reproductive system in adult males, which is associated with oxidative stress in the testes.
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In spite of its excellent electrical, mechanical, and low‐cost characteristics, copper nanowire has fatal issues in the oxidation problem and the lack of biological compatibility, which occasionally outweighs its advantages and limits its usage as electronics or biodevice applications. In this study, a novel wet chemical synthesis method is developed for the oxidation‐free Cu–Au core–shell nanowire based on the prepared Cu nanowire with alkylamine‐mediated synthesis and ligand exchange. The synthesized Cu–Au core–shell nanowire exhibits improved electrical stability against thermal oxidation under the harsh environment of 80 °C and 80% relative humidity. Additionally, to substantiate suitability for the biomedical application, the enhanced chemical stability and biocompatibility are investigated by utilizing the artificial perspiration and the cell culture. As a proof‐of‐concept demonstration, high performance wearable electromyogram (EMG), electrocardiogram (ECG) sensors for electrophysiological monitoring with the Cu–Au core–shell nanowire electrode are demonstrated with superior oxidation‐resistance and biocompatibility even after the harsh environment test. The Cu–Au core–shell nanowire can provide promising, cost‐effective electrode materials for various wearable electronics applications. The issues of copper nanowires in the oxidation and the biocompatibility are addressed in this study by the novel synthesis for the copper‐gold core–shell nanowire based on the copper nanowires with alkylamine‐mediated synthesis and ligand exchange. Furthermore, high performance wearable electrophysiological monitoring sensors with the copper–gold core–shell nanowire electrode are demonstrated with superior oxidation‐resistance and biocompatibility.
Chapter
Metal nanoparticles (NPs) have received much attention from the science and industry community throughout the globe due to various applications in agronomy; modern medicine; and biomedical field as antioxidants anticancer, antibacterial, and antifungal agents. It is also known that the dietary allowance of copper (Cu) is 0.9 mg/day and a 70 kg healthy human body contains 110 mg Cu. The union of nanoscience and nanotechnology with physics, chemistry, and biology has emerged as a foremost approach for the synthesis and biomedical application of Cu and Cu‐based NPs. This green synthesis of Cu and Cu‐based NPs hires several reducing as well as stabilizing agents from biotic resources. Numerous studies of Cu‐based NPs have been suggested for use as a potential antimicrobial, targeted delivery of anticancer drugs, oncology, in vivo imaging, in vitro diagnostic, sensors, and creation of functional nanodevices. This chapter has reviewed the medicinal use of CuONPs anticancer activity in different human cancer cell lines (A549, MCF7, MRC5, HCT‐116, HEp‐2, HeLa, 293T HEK, PC12), and the results showing a dose‐dependent anticancer activity. The researcher demonstrated that these NPs increase oxidative stress by reactive oxygen species (ROS) generation, mitochondrial depolarization, cell cycle arrest, leading to genetically programmed cell death or apoptosis. On the other hand, the excess usage of Cu‐based NPs raise the chance of toxicity to humans, other living beings, and the environment. Moreover, interactive study and explorations of Cu‐based NPs in biomedical applications, risks, safety assessments, and the advantage are essential and challenging.
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Numerous metals have found their application in diagnostics as imaging agents, in therapeutics, etc. and twenty‐first century research has focused its trend on developing nanoparticulate form of metals. These metallic nanoparticles (MNPs) are easy to synthesize and sizes as low as 5 nm can be achieved. The high‐surface area‐to‐volume ratio and varied surface functionalization allow for its application in drug delivery and targeted therapies. The geometry and properties of MNP is quite different and unique, unlike the properties of their bulk form. Such properties often influence its uptake, distribution, elimination, and toxicity. The benefits of MNPs are associated with toxicities as well, with bare metallic nanoparticles reported for their toxicities in in vitro and in vivo models. MNPs generally prove to be toxic due to various reasons like reactive oxygen species (ROS) generation, inducement of oxidative stress, disturbing the integrity of the cytoskeleton, damaging DNA, and inducing rogue cell signaling. These toxicity issues have not convinced regulatory bodies and pose significant hurdles in translating to clinical settings. Attempts have been made to surface modify MNPs with polymers like polyethylene glycol to reduce their opsonization, increase biocompatibility, and reduce toxicity. This chapter provides an insight into the accumulation of MNPs and factors influencing the toxicity of MNP. The research on toxicity and pharmacokinetics of metals along with its application needs ample focus. The toxicity of MNPs needs to be addressed and further extensive research is essential on pharmacokinetics and toxicity studies for successful application and uses in the healthcare sector.
Chapter
As a consequence of industrial development, effluents from various industrial practices augmented the concentration of environmental contaminants on the earth’s surface. Therefore, the materials adopted for decontamination of these environmental contaminants must be environmentally safe and could not produce any toxic side effects to any component of the living organism. In reality, nanoscience and nanotechnology offered the greatest efficiency for the removal of perilous environmental contaminants, and toxicological effects resulted due to the unsafe disposal of these nanoparticles, nanomaterials, and nanocomposites. Herein, we discuss biological and chemical treatment technologies for the mineralization of various environmental contaminants and nanocatalysts’ efficiency toward their complete removal. The second part of this chapter essentially concentrated on toxicological effects generated by the unsafe disposal of nanomaterials/nanocatalysts to the environment. Two noteworthy components of the food cycle are plants and fishes; accumulation, translocation, and biotransformation of nanoparticles/metals/semiconductor nanocomposites in the food cycle are discussed for a better understanding of the underlying relation between catalytic and toxicological effects of nanomaterials.
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Nanotechnology is set to impact a wide range of various fields, including medicine, materials technology, environmental sciences, and engineering/manufacturing. Nanoparticles are categorized depending on their size, composition, shape, and surface functionality. Due to the excessive growth of nanostructured materials (NSMs) in production and industrial applications, human and environmental exposure to them and their possible toxicity issues are inevitable. The main objective of this review is to study NSMs, in particular metallic and metallic oxide nanoparticles, and properties that have a determinative role in their bioimpacts. Nevertheless, the main focus is to provide an overview of NSMs toxicology. Medical and environmental applications of the NSMs are discussed here. Also, key factors on the toxicity of the nanoparticles such as shape, size, chemical composition, and surface functionality are discussed. Finally, toxicity of the nanoparticles is going to be highlighted, and relevant studies are critically compared. This review gives a broad scientific view for improving the functional efficiency of nanomaterials while mitigating their possible adverse and unintended effects on biological systems.
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The purpose of this research was to formulate Polymeric (Chitosan/PEG blended PLGA) nanoparticles containing Pioglitazone as a model drug using the solvent evaporation method. The resultant nanoparticles were characterized by dynamic laser spectroscopy, transmission electron microscopy, atomic force microscopy, and X-ray diffraction. The nanoparticles had a spherical shape with a mean particle diameter of 323 ± 1.15 nm. Furthermore, data from differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) research revealed no drug-polymer interaction. The efficiency of drug encapsulation was determined to be 61.7 ± 2.91%. The formulated nanoparticles also showed improved drug bioavailability in an in vivo system. When compared to the native drug-treated group, blood glucose levels in Pioglitazone-loaded nanoparticle treated streptozotocin caused diabetic rats were reduced dramatically (up to 7 days) to normal levels (up to 6 hours). In albino rats, the nanoparticles' in vivo toxicity investigation revealed no significant changes in behavioral, biochemical, or hematological exams. As a result, the developed system may be useful in achieving a controlled release of the drug, which may help decrease dose frequency and increase patient compliance with pioglitazone for the treatment of type 2 diabetes mellitus.
Thesis
A thorough understanding of the colloidal stability is important to design nanoparticles for drug delivery purposes. In particular, anticipating the in vivo particles disassembly or aggregation is fundamental in order to predict efficacy and toxicity of the nanoformulations. The objectives of this thesis concerned (1) the improvement of the colloidal stability in physiological conditions and (2) the in vitro investigation of the biological behavior of two types of drug nanocarriers: chitosan-iron based nanogels and polydiacetylene micelles.
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Nanomaterials are part of an industrial revolution to develop lightweight but strong materials for a variety of purposes. Single-wall carbon nanotubes are an important member of this class of materials. They structurally resemble rolled-up graphite sheets, usually with one end capped; individually they are about 1 nm in diameter and several microns long, but they often pack tightly together to form rods or ropes of microscopic sizes. Carbon nanotubes possess unique electrical, mechanical, and thermal properties and have many potential applications in the electronics, computer, and aerospace industries. Unprocessed nanotubes are very light and could become airborne and potentially reach the lungs. Because the toxicity of nanotubes in the lung is not known, their pulmonary toxicity was investigated. The three products studied were made by different methods and contained different types and amounts of residual catalytic metals. Mice were intratracheally instilled with 0, 0.1, or 0.5 mg of carbon nanotubes, a carbon black negative control, or a quartz positive control and euthanized 7 d or 90 d after the single treatment for histopathological study of the lungs. All nanotube products induced dose-dependent epithelioid granulomas and, in some cases, interstitial inflammation in the animals of the 7-d groups. These lesions persisted and were more pronounced in the 90-d groups; the lungs of some animals also revealed peribronchial inflammation and necrosis that had extended into the alveolar septa. The lungs of mice treated with carbon black were normal, whereas those treated with high-dose quartz revealed mild to moderate inflammation. These results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.
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Manmade nanoparticles range from the well-established multi-ton production of carbon black and fumed silica for applications in plastic fillers and car tyres to microgram quantities of fluorescent quantum dots used as markers in biological imaging. As nano-sciences are experiencing massive investment worldwide, there will be a further rise in consumer products relying on nanotechnology. While benefits of nanotechnology are widely publicised, the discussion of the potential effects of their widespread use in the consumer and industrial products are just beginning to emerge. This review provides comprehensive analysis of data available on health effects of nanomaterials.
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Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older biokinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.
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Copper toxicosis in Bedlington terriers is an autosomal recessive disorder characterized by excessive hepatic copper accumulation in association with a marked decrease in biliary copper excretion. Recent genetic data have revealed that MURR1, a single copy gene on dog chromosome 10q26, is mutated in this disorder. This gene encodes a 190-amino acid open reading frame of unknown function that is highly conserved in vertebrate species. The Wilson disease protein is a copper transporting ATPase shown to play a critical role in biliary copper excretion. Here we demonstrate that the Wilson disease protein directly interacts with the human homologue of Murr1 in vitro and in vivo and that this interaction is mediated via the copper binding, amino terminus of this ATPase. Importantly, this interaction is specific for this copper transporter, a finding consistent with the observation that impaired copper homeostasis in affected terriers is confined to the liver. Our findings reveal involvement of Murr1 in the defined pathway of hepatic biliary copper excretion, suggest a potential mechanism for Murr1 function in this process, and provide biochemical evidence in support of the proposed role of the MURR1 gene in hepatic copper toxicosis.
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Although copper is an essential micronutrient normally subject to effective homeostatic control, excess dietary intakes can in some circumstances be toxic. Susceptibility to copper toxicosis depends, however, on many factors, including species, genetics, age, and diet. This appears to reflect not only variations in the efficiency of the absorption and excretion of copper but also differences in the intake of other hepatotoxic or protective factors, differences in the cellular distribution of copper, and differences in the expression of specific copper transport and storage proteins. Many of the toxic effects of copper, such as increased lipid peroxidation in cell membranes and DNA damage, are related to its role in the generation of oxygen free radicals.
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Whole-body copper metabolism is difficult to study in human subjects. However, the use of isotopic tracers and kinetics modeling has added a dimension beyond what can be learned in humans by direct measurement. Mechanisms regulating total body copper seem to be strong, given the relatively small and constant body pool, but they are not yet well understood. The efficiency of copper absorption varies greatly, depending on dietary intake. Changes in efficiency of absorption help to regulate the amount of copper retained by the body. In addition, endogenous excretion of copper into the gastrointestinal tract depends heavily on the amount of copper absorbed. When dietary copper is high and more is absorbed, endogenous excretion increases, protecting against excess accumulation of copper in the body. When intake is low, little endogenous copper is excreted, protecting against copper depletion. Regulation is not sufficient with very low amounts of dietary copper (0.38 mg/d) and appears to be delayed when copper intake is high. The use of isotopic tracers and kinetic modeling should aid in elucidating the regulatory mechanisms.
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Copper is an essential micronutrient that plays a vital role as a catalytic co-factor for a variety of metalloenzymes. The redox chemistry of copper also makes it a potentially toxic metal if not properly used. Therefore, elaborate mechanisms have evolved for controlling its cellular uptake, elimination, and distribution. In the last decade, our understanding of the systems involved in maintaining copper homeostasis has improved considerably with the characterization of copper transporters that mediate cellular copper uptake or efflux and with the identification of copper chaperones, a family of proteins required for delivering copper to specific targets in the cell. Despite the distinct roles of these proteins in copper trafficking, all seem able to respond to changes in copper status. Here, we describe recent advances in our knowledge of how copper-trafficking proteins respond to copper deficiency or overload in mammalian cells in order to maintain copper balance.
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The purpose of this study is to evaluate the acute toxicity of oral exposure to nanoscale zinc powder in mice. The healthy adult male and female mice were gastro-intestinally administered at a dose of 5 g/kg body weight with two size particles, nanoscale zinc (N-Zn) and microscale zinc (M-Zn) powder, while one group mice treated with sodium carboxy methyl cellulose was used as the control. The symptoms and mortality after zinc powder treatment were recorded. The effects of particles on the blood-element, the serum biochemical level and the blood coagulation were studied after 2 weeks of administration. The organs were collected for histopathological examination. The N-Zn treated mice showed more severe symptoms of lethargy, vomiting and diarrhea in the beginning days than the M-Zn mice. Deaths of two mice occurred in the N-Zn group after the first week of treatment. The mortalities were confirmed by intestinal obstruction of the nanoscale zinc aggregation. The biochemical liver function tests of serum showed significantly elevated ALT, AST, ALP, and LDH in the M-Zn mice and ALT, ALP, and LDH in the N-Zn mice compared with the controls (P<0.05), which indicated that the liver damage was probably induced by both micro- and nano-scale zinc powders. The clinical changes were observed in the two treated group mice as well. The levels of the above enzymes were generally higher in the M-Zn mice than in the N-Zn mice, which implied that M-Zn powder could induce more severe liver damage than N-Zn. The biochemical renal function tests of serum BUN and CR in the M-Zn mice markedly increased either compared with the N-Zn mice or with the controls (P<0.05), but no significant difference was found between the N-Zn and the control mice. However, severe renal lesions were found by the renal histopathological examination in the N-Zn exposed mice. Therefore, we concluded that severe renal damage could occur in the N-Zn treated mice, though no significant change of blood biochemical levels occurred. Blood-element test showed that in the N-Zn mice, PLT and RDW-CV significantly increased, and HGB and HCT significantly decreased compared to the controls, which indicated that N-Zn powder could cause severe anemia. Besides the pathological lesions in the liver, renal, and heart tissue, only slight stomach and intestinal inflammation was found in all the zinc treated mice, without significant pathological changes in other organs.
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To assess the toxicity of copper nanoparticles (23.5 nm) in vivo, LD(50), morphological changes, pathological examinations and blood biochemical indexes of experimental mice are studied comparatively with micro-copper particles (17 microm) and cupric ions (CuCl(2).2H(2)O). The LD(50) for the nano-, micro-copper particles and cupric ions exposed to mice via oral gavage are 413, >5000 and 110 mg/kg body weight, respectively. The toxicity classes of nano and ionic copper particles both are class 3 (moderately toxic), and micro-copper is class 5 (practically non-toxic) of Hodge and Sterner Scale. Kidney, liver and spleen are found to be target organs of nano-copper particles. Nanoparticles induce gravely toxicological effects and heavy injuries on kidney, liver and spleen of experimental mice, but micro-copper particles do not, on mass basis. Results indicate a gender dependent feature of nanotoxicity. Several factors such as huge specific surface area, ultrahigh reactivity, exceeding consumption of H(+), etc. that likely cause the grave nanotoxicity observed in vivo are discussed.
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Although progress has recently been made toward understanding the health and environmental consequences of these materials, challenges remain for future research.
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It has previously been reported that the in vitro cytotoxic effects of water-soluble fullerene species are a sensitive function of their surface derivatization status. In a recent study, it was reported that doses of an aggregated form of underivatized C60, termed nano-C60, were 3-4 orders of magnitude more toxic to human dermal fibroblasts, lung epithelial cells, and normal human astrocytes when compared to identical exposures of these cell types to a fully derivatized, highly water-soluble derivative, C60(OH)24. Accordingly, the aim of this study was to test and validate these in vitro findings by comparing the in vivo pulmonary toxicity effects in rats of intratracheally instilled nano-C60 and C60(OH)24. In two combined studies, groups of rats were instilled with doses of either 0.2, 0.4, 1.5, or 3.0 mg/kg of nano-C60, C60(OH)24, or alpha-quartz particle types using Milli-Q water as the vehicle. Subsequently, the lungs of vehicle and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, oxidant and glutathione endpoints, airway and lung parenchymal cell proliferation methods, and histopathological evaluation of lung tissue at 1 day, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to both nano-C60 or water-soluble C60(OH)24 produced only transient inflammatory and cell injury effects at 1 day postexposure (pe) and were not different from water instilled controls at any other pe time periods. An increase in lipid peroxidation endpoints vs controls was measured in BAL fluids of rats exposed to 1.5 and 3 mg/kg of nano-C60 at 1 day and 3 month pe time points. In addition, no adverse lung tissue effects were measured at 3 months postinstillation exposures to the highest dose of the two types of fullerenes. In contrast, pulmonary exposures to quartz particles in rats produced dose-dependent lung inflammatory responses characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. The results demonstrated little or no difference in lung toxicity effects between the two fullerene samples when compared to controls, and these data are not consistent with the previously reported in vitro effects. The findings exemplify both the difficulty in interpreting and extrapolating in vitro toxicity measurements to in vivo effects and highlight the complexities associated with probing the relevant toxicological responses of fullerene nanoparticle systems.