REDUCTION OF CISPLATINUM-INDUCED NEPHROTOXICITY BY ZINC HISTIDINE COMPLEX - THE POSSIBLE IMPLICATION OF NITRIC-OXIDE

Cisplatin is a prominent member of the effective broad spectrum antitu mor drugs. The clinical usage of cisplatin is, however, restricted due to some adverse side effects including renal toxicity. The present st udy demonstrates the protective effect of a Zinc-chelate of histidine, [Zn-Hist], against cisplatin induced nephrotoxicity and gastrointesti nal toxicity as shown by decreases in BUN, creatinine and lower incide nce of diarrhoea. The observed inhibition in cisplatin induced renal a nd hepatic lipid peroxidation by [Zn-Hist] pretreatment, suggests an i mportance for Zn in stabilisation of membrane integrity probably throu gh the displacement of the redox-active metals that may;be responsible for inducing peroxidative damage at target sites. The findings also s uggest that cisplatin may play biochemical role in arginine-metabolism including nitric oxide (NO) production.