PROTECTION BY 4-METHYLTHIOBENZOIC ACID AGAINST CISPLATIN-INDUCED OTOTOXICITY - ANTIOXIDANT SYSTEM

This study was undertaken in order to determine the changes in auditor y brainstem-evoked responses relationship with the changes in the leve ls of GSH, lipid peroxidation and antioxidant enzymes activity in cisp latin-induced ototoxicity and otoprotection by 4-methylthiobenzoic aci d (MTBA). Male Wistar rats in different groups were treated as follows : 1) saline control; 2) cisplatin (16 mg/kg, intraperitoneally); 3) MT BA (250 mg/kg, intraperitoneally), and 4) cisplatin plus MTBA. Post-tr eatment auditory brainstem-evoked responses were performed after three days and the rats were sacrificed and cochleae harvested. The cochlea e were analyzed for glutathione (GSH), antioxidant enzyme activity, an d malondialdehyde levels. The cisplatin injected rats showed a thresho ld elevation of 31.9+/-16.0 dB above the pretreat ment thresholds usin g click stimulus. Rats treated with MTBA plus cisplatin did not show s ignificant elevation of hearing threshold. Cisplatin plus MTBA adminis tration 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, cata lase, glutathione peroxidase (GSH-peroxidase), and glutathione reducta se (GSH-reductase) activities (57%, 83%, 78% and 58% of control). Coch lear superoxide dismutase, catalase and GSH-reductase activities and M DA levels were restored in the rats injected with cisplatin plus MTBA, compared to cisplatin alone. It is concluded that the protection conf erred by MTBA against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant system.