Experimental study of the protective effect of glutathione against cisplatin-induced nephrotoxicity

Abstract

Glutathione (GSH) is the most important intracellular thiol-compound which participates in the detoxification mechanisms of the cell. Its high affinity to react with platinum complexes would give rise to lower or non-toxic metabolites and prevent cisplatin nephrotoxicity. In order to determine if GSH can protect against cisplatin-induced renal toxicity, 120 female Wistar rats received LD-100 or LD-50 of cisplatin with or without GSH, at two different dose levels and by two different routes. Biochemical and histological changes as survival was observed in each group. The administration of GSH did not modify cisplatin LD-100. When cisplatin LD-50 was used, a significant improvement in the survival rate was observed in the group which received GSH as chemoprotector (100% vs 40%). The average values of urea and creatinine were significantly lower in the group treated with GSH (115 vs 370 mg/dl and 1.07 vs 4.02 mg/dl respectively). The degree of the tissue injury was also lower in the GSH group. The administration of GSH prior to cisplatin reduces its nephrotoxicity in this animal model. Further clinical trials are necessary to verify this protective effect when cisplatin is used as a cyclic administration and at different dose levels.