Toxicity Of Copper Nanoparticles Research Articles

Assessing cardiovascular toxicity in zebrafish embryos exposed to copper nanoparticles

The toxicity of copper nanoparticles (CuNPs) to aquatic animals, particularly their effects on the cardiovascular system, has not been thoroughly investigated. In the present study, zebrafish embryos were used as a model to address this issue. After exposure to different concentrations (0.01, 0.1, 1, and 3 mg/L) of CuNPs for 96 h (4 to 100 h post-fertilization), cardiac parameters of the heart rate (HR), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and cardiac output (CO), and vascular parameters of the aortic blood flow velocity (ABFV) and aortic diameter (AD) were examined by a video-microscopic method. Morphologically, CuNPs induced concentration-dependent pericardial edema. Although CuNPs did not alter the HR, they significantly reduced the EDV, SV, and CO at ≥0.1 mg/L, the ESV and EF at 3 mg/L, the ABFV at ≥0.1 mg/L, and the AD at ≥1 mg/L. Transcript levels of several cardiac genes, nppa, nppb, vmhc, and gata4, were also examined. CuNPs significantly suppressed nppa and nppb at ≥0.1 mg/L, gata4 at ≥0.01 mg/L, and vmhc at 1 mg/L. This study demonstrated that CuNPs can induce cardiovascular toxicity at environmentally relevant concentrations during fish embryonic development and highlight the potential ecotoxicity of CuNPs to aquatic animals.

Tissue-specific toxic effects of nano-copper on zebrafish

Understanding the behavior and potential toxicity of copper nanoparticles (nano-Cu) in the aquatic environment is a primary way to assess their environmental risks. In this study, RNA-seq was performed on three different tissues (gills, intestines, and muscles) of zebrafish exposed to nano-Cu, to explore the potential toxic mechanism of nano-Cu on zebrafish. The results indicated that the toxic mechanism of nano-Cu on zebrafish was tissue-specific. Nano-Cu enables the CB1 receptor of the presynaptic membrane of gill cells to affect short-term synaptic plasticity or long-term synaptic changes (ECB-LTD) through DSI and DSE, causing dysfunction of intercellular signal transmission. Imbalance of de novo synthesis of UMP in intestinal cells and its transformation to UDP, UTP, uridine, and uracil, resulted in many functions involved in the pyrimidine metabolic pathway being blocked. Meanwhile, the toxicity of nano-Cu caused abnormal expression of RAD51 gene in muscle cells, which affects the repair of damaged DNA through Fanconi anemia and homologous recombination pathway, thus causing cell cycle disorder. These results provide insights for us to better understand the differences in toxicity of nano-Cu on zebrafish tissues and are helpful for a comprehensive assessment of nano-Cu's effects on aquatic organisms.

Toxicity Mechanisms of Copper Nanoparticles and Copper Surfaces on Bacterial Cells and Viruses

Copper is a metal historically used to prevent infections. One of the most relevant challenges in modern society are infectious disease outbreaks, where copper-based technologies can play a significant role. Currently, copper nanoparticles and surfaces are the most common antimicrobial copper-based technologies. Despite the widespread use of copper on nanoparticles and surfaces, the toxicity mechanism(s) explaining their unique antimicrobial properties are not entirely known. In general, toxicity effects described in bacteria and fungi involve the rupture of membranes, accumulation of ions inside the cell, protein inactivation, and DNA damage. A few studies have associated Cu-toxicity with ROS production and genetic material degradation in viruses. Therefore, understanding the mechanisms of the toxicity of copper nanoparticles and surfaces will contribute to developing and implementing efficient antimicrobial technologies to combat old and new infectious agents that can lead to disease outbreaks such as COVID-19. This review summarizes the current knowledge regarding the microbial toxicity of copper nanoparticles and surfaces and the gaps in this knowledge. In addition, we discuss potential applications derived from discovering new elements of copper toxicity, such as using different molecules or modifications to potentiate toxicity or antimicrobial specificity.

Aging of Copper Nanoparticles in the Marine Environment Regulates Toxicity for a Coastal Phytoplankton Species.

Environmental conditions in aquatic ecosystems transform toxic chemicals over time, influencing their bioavailability and toxicity. Using an environmentally relevant methodology, we tested how exposure to seawater for 1-15 weeks influenced the accumulation and toxicity of copper nanoparticles (nano-Cu) in a marine phytoplankton species. Nano-Cu rapidly agglomerated in seawater and then decreased in size due to Cu dissolution. Dissolution rates declined during weeks 1-4 and remained low until 15 weeks, when the large agglomerates that had formed began to rapidly dissolve again. Marine phytoplankton species were exposed for 5-day periods to nano-Cu aged from 1 to 15 weeks at concentrations from 0.01 to 20 ppm. Toxicity to phytoplankton, measured as change in population growth rate, decreased significantly with particle aging from 0 to 4 weeks but increased substantially in the 15-week treatment due apparently to elevated Cu dissolution of reagglomerated particles. Results indicate that the transformation, fate, and toxicity of nano-Cu in marine ecosystems are influenced by a highly dynamic physicochemical aging process.

Copper nanoparticles lead to reproductive dysfunction by affecting key enzymes of ovarian hormone synthesis and metabolism in female rats

Studies on the general toxicity of copper nanoparticles (Cu NPs) have been conducted extensively, but their effects on reproductive toxicity remain unclear. In this study, we evaluated the toxic effect of Cu NPs on pregnant rats and their litter. The comparative in vivo toxicity of Cu ions, Cu NPs, and Cu microparticles (MPs) was studied in a 17-day repeated oral-dose experiment at the doses of 60, 120, and 180 mg/kg/day in pregnant rats. The pregnancy rate, mean live litter size, and number of dams decreased when exposed to Cu NPs. Moreover, Cu NPs caused a dose-dependent increase in ovarian Cu levels. The metabolomics results showed that Cu NPs caused reproductive dysfunction by altering sex hormones. In addition, in vivo and in vitro experiments showed that the ovarian cytochrome P450 enzymes (CYP450), responsible for hormone production, were significantly upregulated, whereas the enzymes responsible for hormone metabolism were significantly inhibited, resulting in a metabolic imbalance in some ovarian hormones. Furthermore, the results revealed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways significantly participated in the regulation of ovarian CYP enzyme expression. Overall, the results of the in vivo and in vitro toxicity experiments with Cu ions, Cu NPs, and Cu MPs suggested that toxicity from nanoscale Cu particles poses a more serious reproductive threat than microscale Cu as Cu NPs could directly damage the ovary and affect the metabolism of ovarian hormones.

Emilia sonchifolia leaf extract-mediated green synthesis, characterization, in vitro biological activities, photocatalytic degradation and in vivo Danio rerio embryo toxicity of copper nanoparticles.

The green-mediated synthesis of copper nanoparticles is of great interest in nanotechnology and is regarded as a low-cost and environmentally beneficial method. Herein, Emilia sonchifolia leaf extract was employed as a reducing and capping agent for the green production of copper nanoparticles. In this work, we focused on the in vivo and in vitro biological studies of copper nanoparticles, which were evaluated in zebrafish (Danio rerio) embryos. The biological effects from the in vitro studies of the copper nanoparticles included cytotoxicity (in human cells) and anti-diabetic, anti-inflammatory, and antibacterial activity. Furthermore, the effectiveness of the greenly produced copper nanoparticles for photocatalysis was also evaluated, and then SEM-EDX, FTIR, XRD, TGA and UV-vis spectroscopy were used to characterise the copper nanoparticles. The results of the toxicity test on zebrafish embryos demonstrated that the green-produced copper nanoparticles had a significantly low harmful effect. According to the results, the copper nanoparticles showed dose-dependent cytotoxicity against human keratinocytes (HaCaT) and human breast cancer cells (MCF-7), which was higher than that of the Emilia sonchifolia leaf extract. The green copper nanoparticles also demonstrated more potent anti-inflammatory, antibacterial and anti-diabetic properties. In the photocatalytic experiment, the produced copper nanoparticles successfully degraded the organic methylene blue dye. Thus, it can be concluded that copper nanoparticles can be employed for drug administration in both in vitro and in vivo settings in biomedical applications. Additionally, as catalysts, these copper nanoparticles can be employed for the removal of organic dyes.

Perilla frutescens (Linn.) Britt Leaves Extract Mediated Green Synthesis, Characterization, In Vitro Biological Activities and Embryo Toxicity of Copper Nanoparticles

AbstractThis work aims to evaluate biological activities and toxicity of copper nanoparticles (CuNPs) synthesized from Perilla frutescens (Linn.) Britt leaves extract. Microscopic techniques showed the poly dispersed CuNPs with a size of 30–65 nm and high resolution X‐ray diffraction (HR‐XRD) revealed the face centered cubic Cu. CuNPs significantly inhibited the growth of few human pathogenic bacteria namely, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium and Bacillus cereus and a fungal pathogen, Alternaria alternata at 40 μg/40 μl concentration. Mode of action of CuNPs against the bacterial pathogens was demonstrated using biological transmission electron microscope (Bio‐TEM). >60 % inhibition was observed against MCF‐7 cells at 160 μg/ml of CuNPs and the apoptotic morphology was confirmed using ethidium homodimer and casein staining. Finally, the toxicity of CuNPs was studied using zebrafish embryo and higher toxic effects were recorded even at 1.5 μg/ml of CuNPs. Therefore, the toxicity of CuNPs must be thoroughly studied.

Exposure of Copper Nano-Particles (CuNPs) Impairs Developmental Stages and Hatchability in the Fresh Water Snail Indoplanorbis exustus (Planorbidae: Pulmonate)

Pollution of water bodies by humans, in our day-to-day activities impairs the quality of water, thereby making the water sources unsuitable for aquatic fauna and also for human health. Various sources of pollutants in excess may negatively affect the diversity of living organisms. The evolving growth of nanotechnology has attracted a great deal of attention due to its concern in assessing their environmental and health safety. The present study was conducted to investigate toxicity of copper nanoparticles (CuNP) on the development of fresh water snail Indoplanorbis exustus. Acclimatized snails were exposed to increasing concentration of CuNP for 96 h and acute toxicity experiment was carried out to determine LC50, followed by exposure of snails to sublethal concentrations of CuNP to observe developmental deformities and to estimate percentage hatchability and survivability of young ones. The projected LC50 value for 96h of CuNPs was found to be 5.8mg/L, followed by exposure to sub-lethal concentrations of 1/6th(0.96mg/L), 1/5th(1.16mg/L), 1/4th(1.45mg/L), and 1/3th (1.93mg/L). The highest concentration of (1.93mg/L;1/3thof LC50) retarded hatching and caused morphological deformities in the larvae. However, no significant difference was observed in the weight of embryos in 7 days. These results revealed that CuNP exposure at sub lethal concentrations exerted developmental stress.
 HIGHLIGHTS
 
 Most of the invertebrate models used in aquatic toxicity are from phylum Mollusca, the gastropods are considered as the best model organisms for NPs toxicity because they are adapted to various environmental disturbances due to their dual habitat, easy availability, high fecundity, small size, short generation time and adaptability.
 Snails, Indoplanorbis exustus were exposed to increasing concentration of copper nanoparticles (CuNPs) for 96 h and acute toxicity experiment was carried out to determine LC50, followed by exposure of snails to sublethal concentrations of CuNPs to observe developmental deformities and to estimate percentage hatchability and survivability of young ones
 The highest concentration of (1.93 mg/L; 1/3th of LC50) retarded hatching and caused morphological deformities in the larvae. However, no significant difference was observed in the weight of embryos in 7 days. These results revealed that CuNP exposure at sub lethal concentrations exerted developmental stress on snails

Vitamins E and C attenuates liver injury induced by copper nanoparticle in Rats (Rattus norvegicus)

Nanoparticles are widely used in many different fields, and production. However, the ingestion of nanoparticles from environmental pollution may have significant health impacts, which are currently poorly understood. In this study we aimed to investigate the cellular toxicity of copper nanoparticles on liver tissue of Rat, and also investigate the role of vitamin E and C, separately or together, in reducing the cellular damage that may be caused by copper nanoparticles. In this study 56 (5–6) weeks old rats with a weight of 120 ± 10 grams were divided into seven groups, treated with copper nanoparticles for four weeks, then treated with vitamins, either alone or together, for another four weeks where is control. Rats were treated with copper nanoparticles showed changes in the ultrastructure of the liver tissue, in which there was a clear decrease in the number of cellular organelles in hepatocytes. Which show small in their size, and had irregular nuclear envelopes, swelling of the mitochondria, shortening of their cristae and effects on their matrix, an increase in the size of lysosomes, an increase in the number of lipid droplets, and an expansion of the Disse spaces. The treatment with vitamins C or E or both, marked improvement was found in the size and number of organelles. The cells returned to almost their normal state. We concluded that vitamins C and E have a positive role in reducing the toxic effects of copper nanoparticles. We recommended their use in doses of 250 mg/kg/day.

Cu-based nanoparticle toxicity to zebrafish cells regulated by cellular discharges

Cellular transport of metal nanoparticles (NPs) is critical in determining their potential toxicity, but the transformation of metal ions released from the internalized NPs is largely unknown. Cu-based NPs are the only metallic-based NPs that are reported to induce higher toxicity compared with their corresponding ions, likely due to their unique cellular turnover. In the present study, we developed a novel gold core to differentiate the particulate and ionic Cu in the Cu2O microparticles (MPs), and the kinetics of bioaccumulation, exocytosis, and cytotoxicity of Au@Cu2O MPs to zebrafish embryonic cells were subsequently studied. We demonstrated that the internalized MPs were rapidly dissolved to Cu ions, which then undergo lysosome-mediated exocytosis. The uptake rate of smaller MPs (130 nm) was lower than that of larger ones (200 nm), but smaller MPs were dissolved much quickly in cells and therefore activated the exocytosis more quickly. The rapid release of Cu ions resulted in an immediate toxic action of Cu2O MPs, while the cell deaths mainly occurred by necrosis. During this process, the buffering ability of glutathione greatly alleviated the Cu toxicity. Therefore, although the turnover of intracellular Cu at a sublethal exposure level was hundred times faster than the basal values, labile Cu(I) concentration increased by only 2 times at most. Overall, this work provided new insights into the toxicity of copper NPs, suggesting that tolerance to Cu-based NPs depended on their ability to discharge the released Cu ions.

New insights into mechanisms of copper nanoparticle toxicity in freshwater algae Chlamydomonas reinhardtii: Effects on the pathways of secondary metabolites

The effects of copper nanoparticles (Cu-NPs), including their stability in the medium, were studied with the green unicellular algae Chlamydomonas reinhardtii (CC-125). Cu-NPs were synthesized and characterized. Cu-NP particles were uniform, regular, and largely spherical, and they had smooth surfaces; the average size was estimated to be 137.4 ± 2.1 nm. Chlamydomonas cells were cultivated for 96 h under controlled conditions in the presence of Cu-NPs, according to OECD guidelines, and then subjected to toxicological bioassays. Based on scanning electron microscopy (SEM) observations, the effects of Cu-NPs resulted in part from the dissolution of nanoparticles (NPs) and the action of copper itself, which shows the importance of studying NP stability in the testing environment. In this assay, deleterious effects were enhanced by increasing Cu-NP concentrations (5, 10, 25, 50, and 100 mg/L). Concentrations higher than 25 mg/L exhibited extreme toxicity. We confirmed the known toxic effects of metal NPs, namely, growth inhibition, reduction of chlorophyll levels in cells, cell penetration and increased ROS production. Attention was also paid to select underexplored metabolites, which were studied with a LC-MS/MS system. Treatments caused changes in metabolites profiles, and levels of p-hydroxybenzaldehyde and protocatechuic acid were especially enhanced, suggesting their positive roles in the antioxidant defence response. Furthermore, a repeatable increase in suberic acid levels was observed for various stress conditions tested, and we expect that this was the result of lipid peroxidation.

The possible role of vitamins E and C in reducing the toxicity of copper nanoparticles in the kidney and liver of the rats (Rattus norvegicus)

This study aims to ascertain the extent of accumulation of copper in the tissue of kidneys and liver, in addition to elucidate the effects of toxic nanoparticles on the kidneys and liver’s functions. Also it aims to measure some of the standards of antioxidants. We randomly had divided 56 rats (Rattus norvegicus) weigh 120 g ± 10 g into seven treatment groups and one of them is a controller. Rats in treatment groups were given 100 mg/kg/day of copper nanoparticles and 250 mg/kg/day of vitamins E and C.The obtained results had indicated an accumulation of copper nanoparticles in the liver and kidneys of the rats in the treatment groups. We also found that the accumulation in the liver is significantly more than in the kidneys. Treatment also resulted in the increase of ALT, AST and GGT enzymes level and serum urea and creatinine in blood serum in the copper nanoparticles treated groups. Also there’s increase in level of lipid peroxide and decrease in the level of glutathione in the liver and the kidneys. When we made a comparison between the controlled group with the treated groups by nanoparticle and vitamins, the results had confirmed the effective role of vitamins as antioxidants that reduce the accumulation of nanoparticles in tissues, and returns the level of liver enzymes, Kidney function, lipid peroxide and glutathione to almost normal levels.

Exposure to copper nanoparticles impairs ion uptake, and acid and ammonia excretion by ionocytes in zebrafish embryos

The potential toxicity of copper nanoparticles (CuNPs) to early stages of fishes is not fully understood, and little is known about their effects on ionocytes and associated functions. This study used zebrafish embryos as a model to investigate the toxic effects of CuNPs on two subtypes of ionocytes. Zebrafish embryos were exposed to 0.1, 1, and 3 mg L−1 CuNPs for 96 h. After exposure, whole-body Na+ and Ca2+ contents were significantly reduced at ≥0.1 mg L−1, while the K+ content had decreased at ≥1 mg L−1. H+ and NH4+ excretion by the skin significantly decreased at ≥1 mg L−1. The number of living ionocytes labeled with rhodamine-123 had significantly decreased with ≥0.1 mg L−1 CuNPs. The ionocyte subtypes of H+-ATPase-rich (HR) and Na+/K+-ATPase-rich (NaR) cells were labeled by immunostaining and had decreased with ≥1 mg L−1. Shrinkage of the apical opening of ionocytes was revealed by scanning electronic microscopy. Functional impairment was also reflected by changes in gene expressions, including ion transporters/channels and Ca2+-regulatory hormones. This study shows that CuNP exposure can impair two subtypes of ionocytes and their associated functions, including Na+/Ca2+ uptake and H+/NH4+ excretion in zebrafish embryos.

Influence of calcium and EDTA on copper ion bioavailability in copper nanoparticle toxicity tests improves understanding of nano-specific effects.

Metal-based nanoparticles (NPs) can release metal ions that are toxic to aquatic organisms; however, whether the toxicity is from metal ions rather than unique "nano-scale" effects of the NPs is unresolved. The present study aimed to compare the toxicity of Cu2+ and Cu-NPs in larval zebrafish (Danio rerio) to clarify whether toxic effects are attributable to release of Cu ions and to determine the effect of the chelating agent ethylenediaminetetraacetic acid (EDTA) and calcium hardness (as CaCO3) on the Cu toxicity. First, the acute toxicity (96-h lethality) of Cu-NPs was determined in comparison to aqueous Cu in larvae exposed to CuSO4, and subsequently, sublethal tests with Cu-NPs and CuSO4 were conducted with additions of EDTA or calcium ions to evaluate alterations in expression of metallothionein-2 (MT2) gene transcripts (quantitative real-time polymerase chain reaction). Acute toxicity of Cu in larvae exposed to CuSO4 was greater (LC50 = 226 µg Cu/L) than for larvae exposed to Cu-NPs (LC50 = 648 µg Cu/L). The expression of MT2 increased with Cu concentration (p < 0.05), and the slope of the linear regression was significantly greater in fish exposed to CuSO4 (slope = 0.090) compared to Cu-NPs (slope = 0.011). Cu2+ was 2.9-fold more toxic than Cu-NPs. The presence of 5 mg/L EDTA and 220 mg/L CaCO3 significantly reduced the expression of MT2 (1.8-fold for EDTA, 2.3-fold for CaCO3) in larvae exposed to CuSO4. For larvae exposed to Cu-NPs, the presence of EDTA reduced the expression of MT2 (1.7-fold) relative to Cu-NP concentration. While Cu-NPs induced MT2 expression, the differences in concentration relationships of MT2 expression between Cu-NPs and CuSO4 indicated that factors other than release of Cu ions from Cu-NPs influenced acute toxicity of Cu-NPs. The conclusion drawn from this ecotoxicological risk assessment was that EDTA and calcium significantly decreased Cu toxicity in freshwater fish.

Review of Copper and Copper Nanoparticle Toxicity in Fish.

This review summarizes the present knowledge on the toxicity of copper and copper nanoparticles (CuNPs) to various fish species. In previous decades, the excessive usage of metal and metallic nanoparticles has increased significantly, increasing the probability of the accumulation and discharge of metals in various trophic levels of the environment. Due to these concerns, it is important to understand the toxicity mechanisms of metals and metallic nanoparticles before they lead to unhealthy effects on human health. In this review paper, we specifically focus on the effect of metal copper and CuNPs on different fish organs under different physiochemical parameters of various water bodies. Nowadays, different forms of copper have distinctive and specific usages, e.g., copper sulfate is a well-established pesticide which is used to control the growth of algae in lakes and ponds. Deactivating the fungi enzymes prevents fungal spores from germinating. This process of deactivation is achieved via the free cupric ions, which are established as the most toxic forms of copper. Complexes of copper with other ligands may or may not be bioavailable for use in aquatic organisms. On the other hand, CuNPs have shown cost-effectiveness and numerous promising uses, but the toxicity and availability of copper in a nanoparticle form is largely unknown, Additionally, physiochemical factors such as the hardness of the water, alkalinity, presence of inorganic and organic ligands, levels of pH, and temperature in various different water bodies affect the toxicity caused by copper and CuNPs. However, comprehensive knowledge and data regarding the pattern of toxicity for copper metal ions and CuNPs in marine organisms is still limited. In this review, we carry out a critical analysis of the availability of the toxicological profiles of copper metal ions and CuNPs for different fishes in order to understand the toxicity mechanisms of copper and CuNPs. We believe that this review will provide valuable information on the toxicological profile of copper, which will further help in devising safe guidelines for the usage of copper and CuNPs in a sustainable manner.

Growth inhibition of the microalgae Skeletonema costatum under copper nanoparticles with microplastic exposure

In order to investigate the combined toxicities of copper nanoparticles (nano-Cu) with microplastic on microalgae Skeletonema costatum, growth inhibition tests were carried out. The toxic effects of copper nanoparticles and microplastic on the microalgae under singleness and coexistence conditions were investigated. Both copper nanoparticles and microplastic inhibited the growth of S. costatum. The growth inhibition ratio (IR) increased with the increasing of particle concentrations and incubation time. The toxicity of copper nanoparticles was reduced with the addition of microplastic. The concentrations of Cu2+ in the medium with or without addition of microplastic were determined. It was found that adsorption of Cu2+ on microplastic and aggregation between copper nanoparticles and microplastic are the main reasons for attenuation of toxicity of nano-Cu with adding microplastic. The adhesion and aggregate interactions between microalgae and nanomaterial were also approved by the observations through scanning electron microscopy.

Histopathological Assessment of Hepato-Nephrotoxicity Induced by Nano Copper Particles in Adult Male Albino Rats and the Potential Protective Effect of Alpha Lipoic Acid: A Chronic Study

Background: Copper nanoparticles (CNPs) have unique physical and chemical properties for this reason it was widely used in various medical and non-medical applications. This study aimed to study the toxic effect of copper nanoparticles on liver and kidney through histopathological examination of liver and kidney tissues and if there is improvement of hepato-nephrotoxicity after cessation of exposure and to study the potential protective effect of alpha lipoic acid (ALA) against hepato-nephrotoxicity induced by copper nanoparticles. Finding: Histopathological examination of liver and kidney tissues in rats received CNPs showed significant alteration, cessation of exposure can cause slight improvement and ALA can cause significant improvement. Conclusion: Copper Nanoparticles have hepato-nephrotoxic effect and ALA can be safely used as a protective agent against CNPs toxicity.

Mechanisms of oxide copper nanoparticles toxicity to microorganisms and ammonia-oxidizing bacteria and recommendations for future study

In recent years, the biological toxicity of oxide copper nanoparticles (CuO NPs) to microorganisms has received some attentions. The toxicity mechanism of CuO NPs can be concluded as follows: (1) CuO NPs facilitate more rapid dissolution of ions than equivalent bulk material, which potentially leading to increased toxicity of CuO NPs; (2) CuO NPs can generate reactive oxygen species (ROS), and potentially disturb the functioning of protein, enzymes and DNA; (3) CuO NPs have high capacity to adsorb biomolecules and interact with biological receptors, they can reach sub-cellular locations leading to potentially higher localized concentrations of ions once those particles start to dissolve or degrade in situ. Ammonia-oxidizing bacteria (AOB) are the main functional bacteria for biological nitrogen removal in the environment. It has been reported that CuO NPs can change the community structures of AOB, however, the toxicity mechanism of CuO NPs to AOB in cytological level is rarely reported. This review aims to evaluate the current understanding of CuO NPs toxicity to microorganisms, as well as to provide a set of pointers and guidelines for future studies to access the toxicity mechanism of CuO NPs to AOB.

Sublethal effects of waterborne copper and copper nanoparticles on the freshwater Neotropical teleost Prochilodus lineatus: A comparative approach

Copper nanoparticles can contaminate the aquatic environment, but their effects on fish and how they may differ from copper salts is not understood. Thus, in this work we compare the sublethal effects of copper nanoparticles (nCu) and copper chloride (Cu) on the freshwater teleost Prochilodus lineatus, known for its sensitivity to copper. Juveniles (n = 8/group) were exposed to 20 μg L−1 of copper as CuCl2 (Cu), 40 μg L−1 of copper nanoparticles (nCu), or only water (control), for 96 h. These concentrations were chosen to achieve similar dissolved copper concentration in both treatments (Cu: 10.29 ± 0.94 μg L−1; nCu: 12.16 ± 1.77 μg L−1). After the exposure, the following biological parameters were evaluated: copper accumulation in the gills, liver, gastrointestinal tract, kidney, and muscle; hematocrit (Ht) and hemoglobin content (Hb); branchial activity of Na+-K+-ATPase (NaKATP), H+-ATPase (HATP), Ca2+-ATPase (CaATP), and carbonic anhydrase (CA); glutathione content (GSH) and lipid peroxidation (LPO) in the liver; acetylcholinesterase activity (AChE) in the brain and muscle; and histopathology of the gills and liver. The gills of Cu-exposed fish were adversely affected, with increased copper content, inhibition of H+-ATPase and Ca2+-ATPase, and histological damage, including proliferation of mitochondria rich cells and/or mucous cells. In addition, LPO levels increased in the liver of Cu-exposed fish, indicating the occurrence of oxidative stress. Exposure to nCu promoted a decrease in Ht and Hb, indicating anemia, and an increase in branchial Na+-K+-ATPase and H+-ATPase activities, which can be an adaptive response to metabolic acidosis. Within the chosen biomarkers and the conditions tested, copper nanoparticles were less toxic than copper. However, the effects promoted by the nanoparticles were different from those promoted by copper. These results emphasize the need for a better understanding of copper nanoparticles toxicity in order to establish safe concentrations and avoid environment impacts.

Copper and copper nanoparticles toxicity and their impact on basic functions in the body.

Copper is a biogenic metal having multiple functions in basic processes in organisms and it is common in all kingdoms of life. Limited intake of copper is a problem; however, doses of copper exceeding the recommended alimentary source are problematic as well and toxicity is soon manifested. Impact of copper nanoparticles on human health is another serious issue taken into consideration in this review. Regarding to copper toxicity, neurodegenerative disorders including Alzheimer and Parkinson diseases are suspected to be linked to copper toxicity or copper can contribute to their progression. Wilson and Menke diseases are also described as examples of copper intolerance. This paper is focused on the description, literature survey and discussion of the current knowledge about copper and copper nanoparticles toxicity and their involvement in various pathological processes (Tab. 6, Fig. 2, Ref. 171). Keywords: reactive oxygen species; Alzheimer disease; acetylcholinesterase; copper; Fenton reaction; disorder; heavy metal; pollution; nanoparticle.