Effect of 4-methylthiobenzoic acid on cisplatin-induced ototoxicity in the rat.
The purpose of this study was to investigate the effectiveness of 4-methylthiobenzoic acid (MTBA) as a protection agent against cisplatin (CDDP)-induced changes in organ of Corti surface structure, compared to electrophysiological changes. Electrophysiological change was assessed using auditory brainstem response (ABR) and morphological changes were assessed using scanning electron microscopy (SEM). Male Wistar rats underwent pre-treatment ABRs in 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) CDDP (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 were sacrificed. Their cochleae were harvested and SEM was used to examine the surface of the organ of Corti, specifically the number of inner hair cells (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. There was a good correlation between ABR threshold changes and hair cell loss in the high frequency region of the cochlea (basal turn), while threshold changes in the lower test frequencies (middle turn) appeared to be the result 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.
Kamimura
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T
Department of Surgery, Southern Illinois University School of Medicine, Springfield 62794-9230, USA.
Whitworth
C A
CA
Rybak
L P
LP
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000506:poisoning*; D003051:Cochlea / Q000166:cytology / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D009925:Organ of Corti / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar
C104409:4-methylthiobenzoic acid; D001565:Benzoates; D002945:Cisplatin