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This study aims to elucidate the molecular mechanism(s) of cisplatin nephrotoxicity and the possible protective effects of antioxidant food supplementation on this toxicity. Twenty eight rats were used throughout the study. Cisplatin was administered intraperitoneally (i.p.) in a single dose (10 mg kg(-1)). Antioxidant food supplementation was started 3 days before cisplatin treatment. In each group (control, cisplatin, cisplatin plus dried black grape and cisplatin plus tomato juice), there were seven animals. Rats were killed 72 h after treatment. The kidneys were removed and prepared for biochemical and histopathological investigations. Oxidant (sensitivity to oxidation, xanthine oxidase enzyme and malondialdehyde level) and antioxidant (superoxide dismutase, glutathione peroxidase and catalase enzymes, and antioxidant potential value) parameters were measured in kidney tissues of the groups. Histopathological examination was also performed. Significant decreases were measured in the renal activities of catalase and glutathione peroxidase enzymes. There was, however, a significant increase in the activity of xanthine oxidase enzyme in the cisplatin-treated animals compared with the control group. The kidney tissue malondialdehyde levels were found to be increased, but sensitivity to oxidation and antioxidant potential values to be decreased in the cisplatin group. In the food supplemented groups, it has been observed that black grape eliminated oxidant stress by increasing antioxidant potential, but tomato did not. Histopathological examination results also revealed significant damage in the kidney tissues from the cisplatin-treated rats. In the black grape group, significant improvements were observed compared with the cisplatin group. In the tomato group, there were also some improvements but to a lesser degree compared with the black grape group. The results suggest that cisplatin treatment causes significant oxidant load to the kidneys through both xanthine oxidase activation and impaired antioxidant defense system, which resulted in accelerated oxidation reactions in the kidney tissue. It is proposed that supplementation of some foods such as black grape which has resveratrol as an antioxidant can provide significant protection against cisplatin nephrotoxicity.

We examined the effect of subacute methidathion (MD) administration on vascular wall damage and evaluated the ameliorating effects of combination of vitamins E and C against MD toxicity. The experimental groups were: rats treated with corn oil (control group), rats treated with 5 mg/kg MD (MD), and rats treated with 5 mg/kg body weight MD plus vitamin E and vitamin C (MD+Vit). The groups were given MD by gavage on 5 days a week for 4 weeks at a daily dose 5 mg/kg (MD and MD+Vit) using corn oil as the vehicle. Vitamins E and C were injected at doses of 50 mg/kg intramuscularly and 20 mg/kg intraperitoneally, respectively, after the treatment with MD in the MD+Vit group. The levels of malondialdehyde (MDA) were determined in the aortic tissue. Histopathological examination was examined in the thoracic aortic tissue. MDA levels were higher in the MD group than the control group and lower in the MD+Vit group than MD group. MD administration led to irregulation, prominent breaks, and fragmentation of the elastic fibers but decrease in the irregulation and fragmantation of the elastic fibers with the combination of vitamins E and C in MD-treated rats. In conclusion, it is likely that subacute MD administration caused vascular wall damage, and that treatment with a combination of vitamins E and C after the administration of MD can reduce vascular wall damage caused by MD.

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