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-methylthiobenzoic acid (MTBA). Male Wistar rats were injected with (1) vehicle control, (2) cisplatin, (3) MTBA, and (4) cisplatin plus MTBA. Rats were euthenized 3 days post-treatment and kidney was isolated and analyzed for platinum concentration, malondialdehyde (MDA), glutathione (GSH and GSSG), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Plasma creatinine increased 508% following cisplatin administration alone, which decreased to 189% with MTBA. Cisplatin-treated rats showed a depletion of renal GSH levels (53%), while cisplatin plus MTBA-injected rats had GSH values close to those of the controls. SOD, CAT, and GSH-Px activities decreased 36, 29, and 38%, respectively, and MDA levels increased 212% following cisplatin administration, which were restored to control levels after MTBA treatment. The renal platinum level depleted significantly with MTBA treatment. The data suggest that cisplatin nephrotoxicity is mediated by depletion in GSH concentration and by impaired activities of SOD, CAT, and GSH-Px, increased lipid peroxidation, and plasma creatinine levels. The protection offered by MTBA against cisplatin nephrotoxicity is related to the reduction in plasma creatinine levels, prevention of GSH depletion and lipid peroxidation, and restoring antioxidant enzyme activity in the kidneys of rats.
Husain
K
K
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794, USA.
Morris
C
C
Whitworth
C
C
Trammel
G L
GL
Rybak
L P
LP
Somani
S M
SM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
C104409:4-methylthiobenzoic acid; D000975:Antioxidants; D001565:Benzoates; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D002945:Cisplatin