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Ultrahigh reactivity provokes nanotoxicity: Explanation of oral toxicity of nano-copper particles
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.
... Additionally, rats showed the electrolyte balance is out of equilibrium (Arafa et al., 2017). Meng et al. (2007) evaluated the effects of ionic, micro, and nano Cu on mice, they suggested that nano-copper caused the greatest intoxication because it had a higher SC level and slower clearance rate. Chen et al. (2006) found that nano-copper turned more dangerous than micro-and ionic-Cu because it included more TBA, ALP, Cr, and BUN. ...
... The administration of CuO NPs affects the parameters of urine, as reported in many studies. Mice administrated with nano-Cu remained higher than micro-Cu NPs presented higher level of SC while Cu decreased (Meng et al., 2007). Additionally, the fact that ionic Cu had a larger concentration of CP than nano-Cu may be the result of serum Cu's binding to CP, an acute phase protein type reactant. ...
Copper oxide nanoparticles (CuO NPs) have received increasing interest due to their distinctive properties, including small particle size, high surface area, and reactivity. Due to these properties, their applications have been expanded rapidly in various areas such as biomedical properties, industrial catalysts, gas sensors, electronic materials, and environmental remediation. However, because of these widespread uses, there is now an increased risk of human exposure, which could lead to short- and long-term toxicity. This review addresses the underlying toxicity mechanisms of CuO NPs in cells which include reactive oxygen species generation, leaching of Cu ion, coordination effects, non-homeostasis effect, autophagy, and inflammation. In addition, different key factors responsible for toxicity, characterization, surface modification, dissolution, NPs dose, exposure pathways and environment are discussed to understand the toxicological impact of CuO NPs. In vitro and in vivo studies have shown that CuO NPs cause oxidative stress, cytotoxicity, genotoxicity, immunotoxicity, neurotoxicity, and inflammation in bacterial, algal, fish, rodents, and human cell lines. Therefore, to make CuO NPs a more suitable candidate for various applications, it is essential to address their potential toxic effects, and hence, more studies should be done on the long-term and chronic impacts of CuO NPs at different concentrations to assure the safe usage of CuO NPs.
... Yalnızca nanobakır ile tedavi edilen tüm fareler, yiyecek kanalı disfonksiyonu, iştahsızlık, ishal ve kusma gibi semptomlar göstermişlerdir. 28 Hücresel savunma sisteminde tiyol grubu içeren antioksidan bileşenler, hücre içi reaktif ara maddelerini temizler. Bu görevi gerçekleştirmek için GSH seviyesinin çok fazla bulunması gerektiği belirlenmiştir. ...
... CuNPler, dalağın küçülmesi, lenfositlerin sayısının azalmasına ve dalak fibrozuna neden olmaktadır. 28 CuNP'lerin reaktif oksijen türlerinin (ROS) ve reaktif nitrojen türlerinin (RNS) oluşmasına ve hücre içi ROS ve NO oluşumunun değişmesine neden olmaktadır. 29 Nano bakırın yüksek dozu, sıçanların karaciğerinde belirgin hasara neden olmaktadır. ...
Giriş: Bakır nanopartiküllerinin (CuNP) günümüzde kullanım sıklığındaki artış insanların bu maddeye olan maruziyetin artması ile sonuçlanmaktadır. Curcuma longa L. ve Naringenin kanser türlerinin oluşma riskinin azaltmakta ve insanlarda koruyucu biyolojik etkilere yardımcı olmaktadır. Amaç: Çalışmamızda, bakır nanopartiküller ile oluşturulmuş oksidatif strese karşı kurkumin ve naringeninin olası koruyucu etkileri incelenmiştir. Yöntem: Çalışmamızda 42 rat 6 gruba ayrılmıştır. Gruplardan biri kontrol grubu iken, diğer gruplara farklı dozlarda kurkumin ve naringenin maddeleri ile CuNP uygulanmıştır. Çalışma sonunda karaciğer dokusu izole edildi ve Süperoksit Dismutaz (SOD), Katalaz (KAT) aktiviteleri, Glutatyon (GSH), Malondialdehit (MDA) düzeyleri ve inflamasyon belirteçleri (IL-1α, IL-1β) araştırılmıştır. Bulgular: Elde edilen bulgular sonucunda, bakır nanopartiküllerin oksidatif stresi arttırdığı ve antioksidan enzim seviyelerinde düşüşe sebep olduğu; kurkumin ve naringeninin ise oksidatif stresi azalttığı ve antioksidan enzim seviyelerini arttırdığı saptanmıştır. Karaciğer dokusunda IL-1α parametresi incelendiğinde, kontrol grubu ve farklı dozlarda kurkumin ve naringenin CuNP ile karşılaştırıldığında, IL-1α düzeyinde azalma saptanmıştır. Bu düşüş istatistiksel olarak anlamlı değildi. IL-1β parametresi, kontrol grubuna kıyasla CuNP grubunda istatistiksel olarak anlamlı bir artış gösterdi (p<0.05). IL-1β düzeyi incelendiğinde diğer gruplara kıyasla CuNP grubunda artma saptanmıştır. Sonuç: İnsanların bakır nanopartiküllere maruz kalması durumunda oluşabilecek zararlı etkilerden korunma ve tedavi için kurkumin ve naringenin kullanılabileceği düşünülebilir.
... 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]. ...
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.
... Oral administration of high doses of CuNPs (1 g/Kg body wt) to mice has been shown to results in gross changes in cellular architecture of liver, spleen and kidney as assessed by tissue morphology and cell histology (Chen et al., 2006). Further, it has also been demonstrated that cupric ions may be released from CuNPs and are responsible for the toxicity via the generation of reactive oxygen species (Meng et al., 2007). A recent study reported in-vivo effects of CuNPs administered orally to rats as a single dose as well as repeated doses at concentration ranging from 312 mg to 2500 mg/kg body weight (Lee et al., 2016). ...
... Nanoparticles (NPs) are found to penetrate the cells and result in the generation of reactive oxygen species (ROS) and oxidative stress, hence disturbing the biological function of the cells (Nel et al. 2006). Previous studies demonstrated the possible adverse effects of CuNPs on the liver, kidney, spleen, lung, and gastrointestinal tract (El Bialy 2020; Chen and Chang 2003;Meng et al. 2007;Ameh and Christie 2019). The female reproductive system is one of the target organs for metal oxide (Hou and Zhu 2017). ...
Copper nanoparticles (CuNPs) have been widely utilized in various applications. Due to its wider application, humans are at risk of its exposure. It has been reported that the exposure of CuNPs can lead to organ accumulation and affect organ toxicity. Recent study suggested that CuNPs can translocate into the uterus and affect uterine injury in rat, whereas uterine toxicity still remains unclear. The uterus is an important female organ which is required to sustain pregnancy. Thus, uterine structure and physiology are important. Therefore, this study hypothesized that CuNPs might have a toxic effect on the uterine features of mice. In this study, we have investigated the potential effects of CuNPs on the uterus of mice both in vivo and in vitro. In in vivo study, two groups of female mice were exposed to 5 and 50 mg/kg/day via oral exposure. In vivo results showed that CuNP treatment decreases the body weight and uterus weight and changes in antioxidant status with low estrogen and progesterone levels. Furthermore, CuNPs up-regulated the expression of caspase3 and down-regulated the expression of apelin receptor (APJ). Immunolocalization of apelin showed low abundance in the CuNP-treated uterus. These results suggest a poor apelin signaling in the uterus after CuNP treatment. The in vivo findings were further supported by the in vitro studies. Firstly, the uterus was cultured with 5 and 40 μg of CuNPs, and in the second in vitro experiment, the uterus was divided into 4 groups: control, 40 μg of CuNPs, 40 μg of CuNPs with apelin, and 40 μg of CuNPs with apelin receptor antagonist (ML221). In vitro study showed that CuNPs could directly induce the oxidative stress and apoptosis as well as changing antioxidant status in the uterus. The in vitro apelin 13 (APLN 13) treatments alleviated the expression of BCL2 and improved the antioxidant markers in CuNP-treated uterus. These results also provided an evidence of apelin-mediated signaling in the CuNP-treated uterus. In summary, our results present evidence that CuNPs can stimulate apoptotic pathways which may lead to uterine impairment due to weak apelin signaling.
... Cytotoxicity, rapid clearance from blood, and limited capacity to overcome multiple physiological barriers are critical issues for the clinical translation of nanomaterials. Nanoparticles can lead to toxic manifestations, resulting in allergy, fibrosis, and organ failure, in addition to hematological, neural, hepatic, splenic, nephron, and pulmonary toxicity [57][58][59][60]. Particle size and surface area also play significant roles in the interaction of materials with biological systems, in addition to particle shape and ratio, surface charge, aggregation capacity, surface coating and roughness, and solvents/media solubility [61] (Figure 1). ...
The term “liver disease” refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.
... Following activation, the infiltrating immune cells produce a large amount of mediators and inflammatory cytokines causing clinical damage to living tissues (11,12). Liver injury is characterized by accelerated serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) (12), and impaired kidney function is reflected by a significant elevation of serum urea and creatinine concentrations (2,13). After activation, the immune cells undergo programmed cell death characterized by extracellular exposure of phosphatidylserine (PS), various caspase activities and DNA fragmentation (14). ...
... Nanoparticles can easily cause the toxicity due to their nanoscale dimensions as they can readily enter into the biological system. Deposition of nanoparticles into the renal tissues and redistribution from the deposition site is also reported [26]. Small sized nanoparticles can easily escape from the phagocytosis while it should be large enough to escape from translocation in tissues and organs. ...
... The introduction of graphene-based nanocomposites as 4D-printed materials for on-time and position shape transformation under the NIR irradiation contributes potentially to the biomedical field [74]. Additionally, we have summarized the size-dependent biocompatibility or toxicity in Table 2 [38,39,[75][76][77][78][79]. ...
Controlling cells using photo-responsive materials is highly indispensable in the current biomedical sector. Considering the potential side effects of nanoparticles, it has become a challenge to control cells with photo-responsive materials. Recent studies have described several methods for controlling cell behavior using nanoparticles subjected to the near-infrared (NIR) laser light operating at the wavelength of 808 nm to 980 nm and at the power densities of 0.33 to 0.72 W·cm−2. The challenge here is the preparation of biocompatible nanoparticles for both in vivo and in vitro studies and understanding cell behavior with an external light source recommended for biological application. Earlier studies have well documented many approaches and associated mechanisms for controlling cell behavior and the interaction between nanoparticles, cells, and appropriate external light sources. In this review, various nanomaterials such as metal nanomaterials and carbon-based nanomaterials are compared systematically regarding the effects of controlling cell behavior and inflammation by studying their mechanisms, route of administration, dose, and adverse effects such as toxicity and the interaction of nanoparticles with a specific wavelength of the light. Future directions should focus on stable and efficient light-responsive materials with minimal cytotoxicity.
... 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. ...
SCCS OPINION ON Copper (nano) and Colloidal Copper (nano) - SCCS/1621/20 - Final 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 Goetz
The SCCS adopted this document by written procedure on 5 March 2021 (49 Pages)
Published:30 December 2021
Ed. Publications Office of the European Union, Luxembourg, Luxembourg (49 pages)
ISSN : 1831-4767
ISBN : 978-92-76-54688-7
DOI : https://data.europa.eu/doi/10.2875/407340
Catalog Number : EW-AQ-22-001-EN-N
https://op.europa.eu/fr/publication-detail/-/publication/c29b4497-21c6-11ed-8fa0-01aa75ed71a1
https://op.europa.eu/fr/publication-detail/-/publication/c29b4497-21c6-11ed-8fa0-01aa75ed71a1/language-en/format-PDF/source-264519490
... 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]. ...
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 ofmultiple 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.
... 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]. ...
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.
... 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). ...
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.
Nanotechnology holds immense promise in revolutionising healthcare, offering unprecedented opportunities in diagnostics, drug delivery, cancer therapy, and combating infectious diseases. This review explores the multifaceted landscape of nanotechnology in healthcare while addressing the critical aspects of safety and environmental risks associated with its widespread application. Beginning with an introduction to the integration of nanotechnology in healthcare, we first delved into its categorisation and various materials employed, setting the stage for a comprehensive understanding of its potential. We then proceeded to elucidate the diverse healthcare applications of nanotechnology, spanning medical diagnostics, tissue engineering, targeted drug delivery, gene delivery, cancer therapy, and the development of antimicrobial agents. The discussion extended to the current situation surrounding the clinical translation and commercialisation of these cutting-edge technologies, focusing on the nanotechnology-based healthcare products that have been approved globally to date. We also discussed the safety considerations of nanomaterials, both in terms of human health and environmental impact. We presented the in vivo health risks associated with nanomaterial exposure, in relation with transport mechanisms, oxidative stress, and physical interactions. Moreover, we highlighted the environmental risks, acknowledging the potential implications on ecosystems and biodiversity. Lastly, we strived to offer insights into the current regulatory landscape governing nanotechnology in healthcare across different regions globally. By synthesising these diverse perspectives, we underscore the imperative of balancing innovation with safety and environmental stewardship, while charting a path forward for the responsible integration of nanotechnology in healthcare.
Graphical abstract
Nanotechnology arising in wide-ranging areas, covers extensively different ranges of approaches attained from fields such as biology, chemistry, physics, and medicine engineering. Nanoparticles are a necessary part of nanotechnology effectually applied in the cure of a number of diseases. Nanoparticles have gained significant importance due to their unique properties, which differ from their bulk counterparts. These distinct properties of nanoparticles are primarily influenced by their morphology, size, and size distribution. At the nanoscale, nanoparticles exhibit behaviours that can enhance therapeutic efficacy and reduce drug toxicity. Their small size and large surface area make them promising candidates for applications such as targeted drug delivery, where they can improve treatment outcomes while minimizing adverse effects. The harmful effects of nanoparticles on the environment were critically investigated to obtain appropriate results and reduce the risk by incorporating the materials. Nanoparticles tend to penetrate the human body, clear the biological barriers to reach sensitive organs and are easily incorporated into human tissue, as well as dispersing to the hepatic tissues, heart tissues, encephalum, and GI tract. This study aims to examine a wide variety of nanoparticles, focusing on their manufacturing methods, functional characteristics, and interactions within biological systems. Particular attention will be directed towards assessing the toxicity of nanoparticles in different organs and physiological systems, yielding a thorough comprehension of their potential health hazards and the processes that drive nanoparticle-induced toxicity. This analysis will also emphasize recent developments in nanoparticle applications and safety assessment methodologies.
Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary health. Despite global efforts to mitigate legacy pollutants, the continuous introduction of new substances remains a major threat to both human and ecosystem health. In response, global initiatives are focusing on risk assessment and regulation of emerging contaminants, as demonstrated by the establishment of the UN’s Intergovernmental Science-Policy Panel on Chemicals, Waste, and Pollution Prevention. This review identifies the sources and impacts of emerging contaminants on planetary health, emphasizing the importance of adopting a One Health approach. Strategies for monitoring and addressing these pollutants are discussed, underscoring the need for robust and socially equitable environmental policies at both regional and international levels. Urgent actions are needed to transition towards sustainable pollution management practices to safeguard our planet for future generations.
Nanotechnology has played a prominent role in biomedical engineering, offering innovative approaches to numerous treatments. Notable advances have been observed in the development of medical devices, contributing to the advancement of modern medicine. This article briefly discusses key applications of nanotechnology in tissue engineering, controlled drug release systems, biosensors and monitoring, and imaging and diagnosis. The particular emphasis on this theme will result in a better understanding, selection, and technical approach to nanomaterials for biomedical purposes, including biological risks, security, and biocompatibility criteria.
In the article reviewed and discussed literature data on biological properties of nanomaterials. The biosafety of nanomaterials is a complex and multifaceted issue that demands a comprehensive, science-based approach. Modern environmental and economic factors should be considered in this regard. The EU’s nanotechnology policy is based on ‘an integrated, safe and responsible approach’ (Communication from the Commission to the European Parliament, the Council and the European Economic and Social Committee. Regulatory aspects of nanomaterials. SEC(2008) 2036 / COM(2008) 366 final). Based on the findings of toxicity and antimicrobial activity studies, metal nanoparticles appear to be a favorable choice as antibacterial agents in developing new disinfectants. However, further measures must be taken to ensure the safe and environmentally friendly use of metal nanoparticles (MeNPs). To achieve this, it is crucial to establish toxicity parameters for MeNPs of various compositions, sizes, and concentrations. These parameters must be compared and evaluated alongside the potential effects of MeNPs on laboratory and target animals (in vivo), as well as their antibacterial performance against microorganisms of different strains (in vitro). Thus, the investigation of possible hazards associated with the use of metal nanoparticles can be effectively achieved by analyzing the fundamental systemic characteristics of biological systems under both in vivo and in vitro conditions, taking into account various aspects such as physiological, biochemical, immunological, genetic and cytological responses that may be affected by toxic effects. The literary sources analysis and article publication were conducted under the National Research Foundation of Ukraine project No. 2021.01/0076 'Development of a novel, nanoparticle-based disinfectant for deactivation of pathogens causing emergent infectious diseases'
The expanding use of nanoparticles in a wide range of applications has brought to light the need to adopt an integrated approach regarding their synthesis, use, recovery and handling.
This book covers the intense research field of nanoparticle utilization as remediation agents for toxic pollutants, and pays special attention to their post-application recovery, the monitoring of their fate when released, and life cycle analysis. The reader may therefore evaluate the prospects and limitations of these technologies through the prism of sustainability demands.
Several chapters summarize successful applications of single or multi-phase nanoparticles for drinking water purification, wastewater and gas-stream treatment and soil consolidation. Importantly, they evaluate the potential scale-up for real-world applications that need to compete with traditional treatment methods.
However, the risk of uncontrolled release into the environment can be a significant drawback to the extended use of nanoparticles. For this reason, a detailed analysis is given to aspects of their post-use recycling and regeneration, determination of release pathways, risk assessment methods and life cycle evaluation studies, highlighting the importance of preventing the unintended release of nanoparticles into the environment.
This book will be a valuable resource for anyone looking at the development of nanoparticles with a view to environmental remediation strategies.
Owing to their unique characteristic features (e.g., nano-scaled dimensions, surface charge, surface chemistry, thermodynamics, morphology, etc.), diversity of functionalization, and great penetrability to body tissues, nanomaterials have been widely employed in various fields including medical and health sciences. The feasibility and significance of nanomaterials has been well-explored as drug delivery devices, diagnostic tools, vaccination, prognostic agents, and gene therapy; however, substantial evidence on safety of these nanomaterials is lacking. The aim of this study was critical evaluation of available literature on the safety concerns of various nanomaterials and conceptualization of vital factors which might help in mitigating the toxicity caused by these nanomaterials. It has been established that various factors such as particle size, dosage regimen, route of exposure, surface chemistry, degree of aggregation, transmembrane diffusivity, excretion pathway, and immunogenicity play key role in inducing the nanotoxicity. By controlling these factors, interaction of nanomaterials with biological tissues, their penetrability, diffusivity, absorption, distribution, recognition by the immune players, duration of deposition into various body tissues, and clearance from the body can be controlled to avert unintended nanotoxicity. Furthermore, it has been identified that surface functionalization of nanomaterials with diverse moieties such as sodium citrate, polyvinylpyrrolidone (PVP) and/or surfactants could significantly downregulate their nanotoxicity potential and improve their safety profile. Factually, nanotoxicity is a grave concern which should be consider while designing of any nanomaterials to circumvent their detrimental interactions with various biological tissues.
The widespread use and applications of copper oxide nanoparticles (CuO NPs) in daily life make human exposure to these particles inevitable. This study was carried out to investigate the deteriorations in hepatic and serum biochemical parameters induced by CuO NPs in adult male mice and the potential ameliorative effect of l-arginine and quercetin, either alone or in combination. Seventy adult male mice were equally allocated into seven groups: untreated group, l-arginine, quercetin, CuO NPs, arginine + CuO NPs, quercetin + CuO NPs, and quercetin + arginine + CuO NPs. Treating mice with CuO NPs resulted in bioaccumulation of copper in the liver and consequent liver injury as typified by elevation of serum ALT activity, reduction in the synthetic ability of the liver indicated by a decrease in the hepatic arginase activity, and serum total protein content. This copper accumulation increased oxidative stress, lipid peroxidation, inflammation, and apoptosis as manifested by elevation in malondialdehyde, nitric oxide, tumor necrosis factor-α, the expression level of caspase-3 and bax quantified by qPCR, and the activity of caspase-3, in addition to the reduction of superoxide dismutase activity. It also resulted in severe DNA fragmentation as assessed by Comet assay and significant pathological changes in the liver architecture. The study proved the efficiency of quercetin and l-arginine in mitigating CuO NPs-induced sub-chronic liver toxicity due to their antioxidant, anti-inflammatory, and anti-apoptotic properties; ability to inhibit DNA damage; and the potential as good metal chelators. The results of histopathological analysis confirmed the biochemical and molecular studies.
As environmental issues have become the dominant agenda worldwide, the necessity for more environmentally friendly electronics has recently emerged. Accordingly, biodegradable or nature‐derived materials for green electronics have attracted increased interest. Initially, metal‐green hybrid electronics were extensively studied. Although these materials are partially biodegradable, they have high utility owing to their metallic components. Subsequently, C‐framed materials (such as graphite, cylindrical carbon nanomaterials, graphene, graphene oxide, laser‐induced graphene) have been investigated. This has led to the adoption of various strategies for C‐based materials, such as blending them with biodegradable materials. Moreover, various conductive polymers have been developed and researchers have studied their potential use in green electronics. Researchers have attempted to fabricate conductive polymer composites with high biodegradability by shortening the polymer chains. Furthermore, various physical, chemical, and biological sensors that are essential to modern society have been studied using biodegradable compounds. These recent advances in green electronics have paved the way toward their application in real life, providing a brighter future for society.
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Nanotechnology possesses a wide array of materials in the form of nano-tubes, fibres, plates, chips, particles, sensors, and so on; the application of which has dramatically increased over the last few years due to their unique physicochemical characteristics (i.e., catalytic activity as well as optical, electronic, antibacterial, and magnetic properties). However, the exposure to nanoparticles, and consequent threat to human health and the environment are valid concerns because of the magnitude of nanotechnology-based applications, mainly in the pharmaceutical industries during drug designing, targeted drug delivery and disease diagnostics, and manufacturing of commercial products. For this purpose, the majority of nanomaterials are synthesized either from carbon (organic) and/or heavy metals, metal oxides (inorganic). Accordingly, lead, zinc, copper, chromium, iron, cadmium, and their oxides are important inorganic nanomaterials that are discussed in the chapter.
The field of photonics and optoelectronics has opened up new avenues for the development of modern technologies with great impact. Research has progressed from a basic to an advanced level, starting from the atomic level through to the development of an optical system. The contribution to and the advancement in developing an optical system using metal oxides (MOs) abundantly available on the earth’s crust cannot be put at the back. MOs have been explored in the fields of optoelectronics and photonics, and the development of exploring these MOs is still under consideration. MOs extraordinarily differ from conventional group III–V compounds, including silicon, due to their design, electronic properties, charge-transfer mechanism, defect levels, processing of thin films, and optoelectronic properties. An extended list of metal oxides contains some oxide materials, which have great potential for being part of photonic applications; the list of MOs having enhanced photonic and optoelectronic properties includes ZnO, TiO2, MoS2, Co3O4, and so on. For instance, the ZnO-bearing morphological structure of nanowires/nanorods has been used for optoelectronic applications as it enhances UV response due to its wide band gap. TiO2 nanoparticles have also been used in composite form due to their enhanced photocatalytic and photoelectrical performances.
As of late, the research community has shown interest in nanostructured metal oxides and their applications because of their cost-effective, safe, and ecofriendly production procedure and innovative uses in the development of applications in the fields of power storage, photonics, and sensors, as well as clinical and ecological applications. Metal oxide (MO)-based bioinorganic nanocomposites possess exceptional physicochemical properties, and novel biochemical functionalities. Particularly, metal oxide nanostructures of zinc, titanium, zirconium, and copper can be created in an assortment of morphologies, for example, nanoparticles, 3D squares, cuboids, round and hexagonal circles, nanorods, nanowires, tapes, belts, tetra units, and trees, utilizing a range of modest physical and synthetic techniques in powder and colloid forms at the nanostructures stage. Metal oxide nanoparticles offer a one-of-a-kind construction, excellent redox and reactant properties, extreme surface area, and mechanical security as components in biocompatible applications. Thus, metal oxide nanoparticles have attracted sizeable interest in the fields of biomedical therapeutics, biosensing, bioimaging, and biolabeling. This chapter examines the nature of selected nanometer-scale metal oxides with unique properties.
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.
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.
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.
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.
Engineered nanomaterials hold great potential in many sectors of society, not least in medicine. However, the increasing production and use of engineered nanomaterials also raises concerns regarding inadvertent exposure and the potential for adverse effects on human health. The chapter provides an overview of metal and metal oxide nanoparticles, their principal applications, and the potential for human exposure. This is followed by a discussion of general principles of nanoparticle-induced toxicity and methods for toxicity testing of nanomaterials. Careful characterization of material properties is required for a full understanding of nanomaterial toxicity and a section of the chapter is devoted to physicochemical characterization. This is followed by a comprehensive description of the most common metal and metal oxide nanoparticles, with a systematic evaluation of in vitro and in vivo toxicity studies. Finally, an overview of emerging, two-dimensional (2D) metal nanomaterials is provided.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Although progress has recently been made toward understanding the health and environmental consequences of these materials, challenges remain for future research.
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.