Journal
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 34, Issue 1, Pages 67-80Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2011.05.014
Keywords
Copper nanoparticals; Nanotoxicology; Nephrotoxicity; Microarray; Toxicogenomics
Funding
- National Basic Research Program of China [2006CB705602]
- National Grand Science and Technology Special Program for Innovation of New Drugs [2008ZX09305-003]
- National Natural Science Foundation [81001254]
- Beijing Natural Science Foundation [7092079]
- Beijing Science Foundation [Z08030203080818]
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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. (C) 2012 Published by Elsevier B.V.
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