4-METHYLTHIOBENZOIC ACID PROTECTION AGAINST CISPLATIN NEPHROTOXICITY - ANTIOXIDANT SYSTEM

This study investigates the changes in renal antioxidant system after cisplatin administration and the nephroprotection with 4-methylthioben zoic acid (MTBA). Male Wistar rats were injected with (I) vehicle cont rol, (2) cisplatin, (3) MTBA, and (4) cisplatin pins MTBA. Rats were e uthenized 3 days post-treatment and kidney was isolated and analyzed f or platinum concentration, malondialdehyale (MDA), glutathione (GSH an d GSSG), superoxide dismutase (SOD), catalase (CAT), and glutathione p eroxidase (GSH-Px). Plasma creatinine increased 508% following cisplat in administration alone, which decreased to 189% with MTBA. Cisplatin- treated rats showed a depletion of renal GSH levels (53%), while cispl atin plus MTBA-injected rats had GSH values close to those of the cont rols. SOD, CAT, and GSH-Px activities decreased 36, 29, and 38%, respe ctively, and MDA levels increased 212% following cisplatin administrat ion, which were restored to control levels after MTBA treatment. The r enal platinum level depleted significantly with MTBA treatment. The da ta suggest that cisplatin nephrotoxicity is mediated by depletion in G SH concentration and by impaired activities of SOD, CAT, and GSH-Px, i ncreased lipid peroxidation, and plasma creatinine levels. The protect ion offered by MTBA against cisplatin nephrotoxicity is related to the reduction in plasma creatinine levels, prevention of GSH depletion an d lipid peroxidation, and restoring antioxidant enzyme activity in the kidneys of rats. (C) 1996 Society of Toxicology