Toxicity Evaluation of Copper Oxide Nanoparticles
Copper oxide nanoparticles (CuO NPs) have been extensively studied for their toxicological effects across various biological systems. This review synthesizes findings from multiple research papers to provide a comprehensive understanding of the mechanisms and impacts of CuO NP toxicity.
Mechanisms of Toxicity
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Oxidative Stress and Reactive Oxygen Species (ROS) Generation
- CuO NPs induce oxidative stress by generating reactive oxygen species (ROS), which leads to cellular damage and apoptosis. In male rat liver and BRL-3A cells, CuO NPs triggered oxidative stress and endoplasmic reticulum (ER) stress, resulting in apoptosis through pathways involving CHOP, JNK, and Caspase-12. Similarly, in the green alga Chlamydomonas reinhardtii, CuO NPs caused growth inhibition, decreased carotenoid levels, and increased ROS levels, leading to lipid peroxidation of cellular membranes.
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Leaching and Speciation
- The leaching of copper ions from CuO NPs plays a significant role in their toxicity. Complexation-mediated leaching by amino acids was identified as a source of toxicity toward Escherichia coli, leading to increased intracellular ROS and reduced viable cell fractions. The differential toxicity of CuO NPs compared to copper salts is attributed to pH-dependent copper speciation, which results in uncoordinated copper ions causing greater toxicity and cell lysis.
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Protein Oxidation and Cellular Uptake
- In the blue mussel Mytilus edulis, CuO NPs induced protein oxidation, particularly in cytoskeletal proteins and enzymes, as evidenced by increased carbonylation and decreased protein thiols. The uptake of CuO NPs into cells and subsequent oxidative damage were also observed in mouse macrophage cell lines, where surface-modified CuO NPs exhibited varying levels of cytotoxicity and ROS production.
Toxicological Impacts
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Hepatotoxicity and Apoptosis
- In vivo studies on male Wistar rats demonstrated that intranasal instillation of CuO NPs caused liver function impairment, oxidative stress, inflammation, and apoptosis in liver tissue. The administration of antioxidants like n-acetyl cysteine was shown to mitigate these effects, highlighting the role of oxidative stress in CuO NP-induced hepatotoxicity.
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Lung Toxicity
- Inhalation of CuO NPs is a significant concern due to their use in industrial and commercial products. In vitro studies on human lung cells revealed that CuO NPs induce cytotoxicity, oxidative stress, and genetic toxicity through mechanisms involving Cu ion leaching and autophagy. In vivo studies further confirmed oxidative stress, inflammation, and neoplastic lesions in rat lung tissues following intratracheal instillation of CuO NPs.
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Aquatic Toxicity
- The toxicity of CuO NPs in aquatic organisms has been demonstrated in various studies. In Artemia salina, CuO NPs caused significant toxicity across different life stages, with accumulation in the gut being a major factor. In the aquatic plant Myriophyllum spicatum, CuO NPs were less toxic than Cu salts, but still caused morphological and physiological changes due to chronic exposure.
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Intestinal Toxicity
- In human intestinal Caco-2 cell monolayers, CuO NPs disrupted monolayer integrity, induced cytotoxicity, and increased pro-inflammatory cytokine and chemokine transcripts. The shape and copper release from CuO NPs were implicated in their differential toxicity.
Conclusion
The toxicity of copper oxide nanoparticles is multifaceted, involving oxidative stress, leaching of copper ions, protein oxidation, and cellular uptake. These mechanisms lead to significant toxicological impacts across various biological systems, including hepatotoxicity, lung toxicity, and aquatic toxicity. Understanding these mechanisms is crucial for developing safer nanomaterials and mitigating their environmental and health impacts.
References
- Cytotoxic origin of copper(II) oxide nanoparticles: comparative studies with micron-sized particles, leachate, and metal salts.
- Exposure to copper oxide nanoparticles triggers oxidative stress and endoplasmic reticulum (ER)-stress induced toxicology and apoptosis in male rat liver and BRL-3A cell.
- Toxicity of copper oxide nanoparticles in the blue mussel, Mytilus edulis: a redox proteomic investigation.
- Assessment of the lung toxicity of copper oxide nanoparticles: current status.
- Toxicity and accumulation of Copper oxide (CuO) nanoparticles in different life stages of Artemia salina.
- Cutting-edge spectroscopy techniques highlight toxicity mechanisms of copper oxide nanoparticles in the aquatic plant Myriophyllum spicatum.
- Toxicity of surface-modified copper oxide nanoparticles in a mouse macrophage cell line: Interplay of particles, surface coating and particle dissolution.
- Evaluation of toxicity and oxidative stress induced by copper oxide nanoparticles in the green alga Chlamydomonas reinhardtii.
- Surface characteristics, copper release, and toxicity of nano- and micrometer-sized copper and copper(II) oxide particles: a cross-disciplinary study.
- Differential toxicity of copper (II) oxide nanoparticles of similar hydrodynamic diameter on human differentiated intestinal Caco-2 cell monolayers is correlated in part to copper release and shape.