Effect of 4-methylthiobenzoic acid on cisplatin-induced ototoxicity in therat

The purpose of this study was to investigate the effectiveness of 4-methylt hiobenzoic acid (MTBA) as a protection agent against cisplatin (CDDP)-induc ed changes in organ of Corti surface structure, compared to electrophysiolo gical changes. Electrophysiological change was assessed using auditory brai nstem response (ABR) and morphological changes were assessed using scanning electron microscopy (SEM). Male Wistar rats underwent pre-treatment ABRs i n response to clicks, and tone bursts at 2, 4, 8, 16, and 32 kHz. The three groups of rats were injected as follows: (1) MTBA (250 mg/kg, i.p.), (2) C DDP (16 mg/kg, i.p.), (3) CDDP+MTBA. (16 mg/kg, i.p.+250 mg/kg, i.p.). Post -treatment ABRs were performed 3 days after drug administration and rats we re sacrificed. Their cochleae were harvested and SEM was used to examine th e surface of the organ of Corti, specifically the number of inner hair cell s (IHCs) and outer hair cells (OHCs) in the apical, middle and basal turns of the cochlea. Animal weight was measured on the first and final days. The re was a good correlation between ABR threshold changes and hair cell loss in the high frequency region of the cochlea (basal turn), while threshold c hanges in the lower test frequencies (middle turn) appeared to be the resul t of more subtle changes in the cochlea. MTBA provided effective protection against cisplatin-induced ABR threshold changes at all test frequencies as well as hair cell loss. MTBA also protected against body weight loss. (C) 1999 Elsevier Science B.V. All rights reserved.