Gene expression profiling of nephrotoxicity from copper nanoparticles in rats after repeated oral administration.

The goal of this study was to investigate the mechanisms of nanocopper-induced nephrotoxicity by analyzing renal gene expression profiles phenotypically anchored to conventional toxicological outcomes. Male Wistar rats were given nanocopper (50, 100, 200 mg/kg) and microcopper (200 mg/kg) at different doses for 5 days. We found nanocopper can induce widespread renal proximal tubule necrosis in rat kidneys with blood urea nitrogen and creatinine increase. Whole genome transcriptome profiling of rat kidneys revealed significant alterations in the expression of many genes involved in valine, leucine, and isoleucine degradation, complement and coagulation cascades, oxidative phosphorylation, cell cycle, mitogen-activated protein kinase signaling pathway, glutathione metabolism, and others may be involved in the development of these phenotypes. Results from this study provide new insights into the nephrotoxicity of copper nano-particles and illustrate how toxicogenomic approaches are providing an unprecedented amount of mechanistic information on molecular responses to nanocopper and how they are likely to impact hazard and risk assessment.