K. Husain et al., 4-METHYLTHIOBENZOIC ACID PROTECTION AGAINST CISPLATIN NEPHROTOXICITY - ANTIOXIDANT SYSTEM, Fundamental and applied toxicology, 32(2), 1996, pp. 278-284
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