DIETHYLDITHIOCARBAMATE PROTECTION AGAINST CISPLATIN NEPHROTOXICITY - ANTIOXIDANT SYSTEM

This investigation elucidates the role of antioxidant system in cispla tin induced nephrotoxicity and the nephroprotection with diethyldithio carbamate (DDTC). Male Wistar rats were injected with 1) cisplatin; 2) cisplatin + DDTC and 3) vehicle control. Rats were sacrificed three d ays post-treatment and the corticomedullary junction of the kidney was isolated and were analyzed for GSH, GSSG, SOD, CAT, and GSH.Px. Serum creatinine increased (500% of control) following cisplatin administra tion which decreased to 200% of control with DDTC. Cisplatin treated r ats showed depletion of GSH levels, while cisplatin + DDTC injected ra ts had GSH values similar to controls. SOD and GSH.Px activities were found to be 63 and 40% of control following cisplatin administration w hich increased to 109 and 75% of control with DDTC respectively. Our f indings suggest that cisplatin nephrotoxicity is mediated by impaired activities of SOD and GSH-Px enzymes and by GSH depletion. The protect ive mechanism of DDTC against cisplatin nephrotoxicity is related to t he prevention of GSH depletion and restoring SOD and GSH-Px activities in the kidney of rats.