Assessment of Ocular and Cervical Vestibular‐Evoked Myogenic Potentials in Cisptin‐Induced Otolith Toxicity in Guinea Pigs

Abstract

Objectives: (1) Determine if cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potentials oVEMPs are good electrophysiological examinations to represent the degree of cisplatin-induced otolith toxicity. (2) Examine if D-methionine (D-met) pre-injection protects the otolith organs against cisplatin-induced changes of enzyme activities and oxidative status. Methods: Guinea pigs were intraperitoneally injected with sterile 0.9% saline alone, cisplatin (5 mg/kg) alone, D-met (300 mg/kg) alone, or D-met (300 mg/kg) 30 minutes before cisplatin (5 mg/kg) in combination, once daily for 7 consecutive days. Each animal was given the oVEMP and cVEMP tests before and after treatment. Changes in otolithic biochemistry, including membranous Na+, K+-ATPase, and Ca2+-ATPase, lipid peroxidation (LPO), and nitric oxide (NO), were also evaluated. Results: In the cisplatin-treated guinea pigs, the mean amplitudes of cVEMP and oVEMP tests were significantly ( P’s < .05) decreased in comparison with the other 3 groups. In guinea pigs receiving both D-met and cisplatin, their amplitudes of cVEMP and oVEMP tests were significantly larger ( P < .05) than those of the cisplatin group, but smaller ( P < .05) than those of the saline or D-met group. In comparison with the other 3 groups, cisplatin alone group had the lowest ( P < .05) mean Na+, K+-ATPase, and Ca2+-ATPase, and the highest ( P < .05) LPO and NO levels. Conclusions: The cVEMP and oVEMP tests were feasible for the evaluation of cisplatin-related otolith dysfunction. The D-met–mediated improvement in otolith function correlated with a significant attenuation of increased oxidative stress and reduced ATPase activities.