Protection by 4-methylthiobenzoic acid against cisplatin-induced ototoxicity: antioxidant system.
This study was undertaken in order to determine the changes in auditory brainstem-evoked responses relationship with the changes in the levels of GSH, lipid peroxidation and antioxidant enzymes activity in cisplatin-induced ototoxicity and otoprotection by 4-methylthiobenzoic acid (MTBA). Male Wistar rats in different groups were treated as follows: 1) saline control; 2) cisplatin (16 mg/kg, intraperitoneally); 3) MTBA (250 mg/kg, intraperitoneally), and 4) cisplatin plus MTBA. Post-treatment auditory brainstem-evoked responses were performed after three days and the rats were sacrificed and cochleae harvested. The cochleae were analyzed for glutathione (GSH), antioxidant enzyme activity, and malondialdehyde levels. The cisplatin injected rats showed a threshold elevation of 31.9 +/- 16.0 dB above the pretreatment thresholds using click stimulus. Rats treated with MTBA plus cisplatin did not show significant elevation of hearing threshold. Cisplatin plus MTBA administration showed a higher levels of cochlear GSH (5.59 +/- 0.35 nmoles/mg protein) compared to cisplatin alone (4.46 +/- 0.13 nmoles/mg protein). Cisplatin treated rats showed a decrease in superoxide dismutase, catalase, glutathione peroxidase (GSH-peroxidase), and glutathione reductase (GSH-reductase) activities (57%, 83%, 78% and 58% of control). Cochlear superoxide dismutase, catalase and GSH-reductase activities and MDA levels were restored in the rats injected with cisplatin plus MTBA, compared to cisplatin alone. It is concluded that the protection conferred by MTBA against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant system.
Rybak
L P
LP
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794-1222, USA.
Husain
K
K
Evenson
L
L
Morris
C
C
Whitworth
C
C
Somani
S M
SM
D000161:Acoustic Stimulation; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001309:Auditory Threshold / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000201:enzymology* / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
C104409:4-methylthiobenzoic acid; D000970:Antineoplastic Agents; D000975:Antioxidants; D001565:Benzoates; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D002945:Cisplatin