Sm. Somani et al., DIETHYLDITHIOCARBAMATE PROTECTION AGAINST CISPLATIN NEPHROTOXICITY - ANTIOXIDANT SYSTEM, Drug and chemical toxicology, 18(2-3), 1995, pp. 151-170
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.