Influence of resveratrol on oxidative damage in genomic DNA and apoptosis induced by cisplatin

Abstract

Cisplatin is a potent chemotherapeutic agent that has gained widespread use against various malignant tumours in a variety of human malignancies. Like other chemotherapeutic agents, cisplatin is genotoxic and apoptogenic in non-tumour cells and the formation of reactive oxygen species appears to be responsible for these toxicities. The anti-genotoxic and anti-apoptotic effects of resveratrol, a polyphenol found in numerous plant species, against cisplatin-induced genotoxicity and apoptosis in vivo were evaluated by use of standard techniques in somatic and germinal cells of mice. Pre-treatment of mice with resveratrol significantly reduced cisplatin-induced genotoxicity and apoptosis and effectively suppressed the apoptotic signalling triggered by cisplatin. The protective effect of resveratrol was found to be stronger at the higher dose, indicating the dose-dependent effect of resveratrol. Cisplatin induced marked biochemical alterations characteristic of oxidative DNA stress. Prior administration of resveratrol before the cisplatin challenge ameliorated these biochemical markers. In conclusion, this study provides evidence for the first time that resveratrol has a protective role in the abatement of cisplatin-induced genotoxicity and apoptosis in somatic and germinal cells of mice. This activity resides, at least in part, in its radical scavenger activity. Therefore, resveratrol can be a promising chemoprotective agent to avert secondary malignancies and abnormal reproductive outcomes in cured cancer patients exposed to cisplatin, without diminishing its anti-neoplastic activity.