EXPERIMENTAL-STUDY OF THE PROTECTIVE EFFECT OF GLUTATHIONE AGAINST CISPLATIN-INDUCED NEPHROTOXICITY

Glutathione (GSH) is the most important intracellular thiol-compound w hich participates in the detoxification mechanisms of the cell. Its hi gh affinity to react with platinum complexes would give rise to lower or non-toxic metabolites and prevent cisplatin nephrotoxicity. In orde r to determine if GSH can protect against cisplatin-induced renal toxi city, 120 female Wistar rats received LD-100 or LD-50 of cisplatin wit h or without GSH, at two different dose levels and by two different ro utes. 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 surv ival rate was observed in the group which received GSH as chemoprotect or (100% vs 40%). The average values of urea and creatinine were signi ficantly lower in the group treated with GSH (115 vs 370 mg/dl and 1.0 7 vs 4.02 mg/dl respectively). The degree of the tissue injury was als o lower in the GSH group. The administration of GSH prior to cisplatin reduces its nephrotoxicity in this animal model. Further clinical tri als are necessary to verify this protective effect when cisplatin is u sed as a cyclic administration and at different dose levels.