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.
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004050:Ditiocarb / Q000627:therapeutic use*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects
D000975:Antioxidants; D004050:Ditiocarb; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D015500:Chloramphenicol O-Acetyltransferase; D005978:Glutathione; D002945:Cisplatin; D019803:Glutathione Disulfide