Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 189, Issue 1-2, Pages 45-51Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2010.10.014
Keywords
Mitochondria; Cisplatin; Carvedilol; Nephrotoxicity; Oxidative stress; Antioxidant
Funding
- FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)
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Cisplatin is a highly effective chemotherapeutic agent which causes severe nephrotoxicity. Studies have suggested that reactive oxygen species, mainly generated in mitochondria, play a central role in cisplatin-induced renal damage. A wide range of antioxidants have been evaluated as possible protective agents against cisplatin-induced nephrotoxicity; however a safe and efficacious compound has not yet been found. The present study is the first to evaluate the protective potential of carvedilol, a beta-blocker with strong antioxidant properties, against the mitochondrial oxidative stress and apoptosis in kidney of rats treated with cisplatin. The following cisplatin-induced toxic effects were prevented by carvedilol: increased plasmatic levels of creatinine and blood urea nitrogen (BUN); lipid peroxidation, oxidation of cardiolipin; oxidation of protein sulfhydryls; depletion of the non-enzymatic antioxidant defense and increased activity of caspase-3. Carvedilol per se did not present any effect on renal mitochondria. It was concluded that carvedilol prevents mitochondrial dysfunction and renal cell death through the protection against the oxidative stress and redox state unbalance induced by cisplatin. The association of carvedilol to cisplatin chemotherapy was suggested as a possible strategy to minimize the nephrotoxicity induced by this antitumor agent. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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