Diethyldithiocarbamate Protection Against Cisplatin Nephrotoxicity: Antioxidant System

This investigation elucidates the role of antioxidant system in cisplatin induced nephrotoxicity and the nephroprotection with diethyldithiocarbamate (DDTC). Male Wistar rats were injected with 1) cisplatin; 2) cisplatin+DDTC and 3) vehicle control. Rats were sacrificed three days post-treatment and the corticomedullary junction of the kidney was isolated adn were analyzed for GSH, GSSG, SOD, CAT, and GSH.Px. Serum creatinine increased (500% of control) following cisplatin administration which decreased to 200% of control with DDTC. Cisplatin treated rats showed depletion of GSH levels, while cisplatin+DDTC injected rats had GSH values similar to controls. SOD and GSH.Px activities were found to be 63 and 40% of control following cisplatin administration which increased to 109 and 75% of control with DDTC respectively. Our findings suggest that cisplatin nephrotoxicity is mediated by impaired activities of SOD and GSH-Px enzymes and by GSH depletion. The protective mechanism of DDTC against cisplatin nephrotoxicity is related to the prevention of GSH depletion and restoring SOD and GSH-Px activities in the kidney of rats.