Round Window Application of D-Methionine Provides Complete Cisplatin Otoprotection

Abstract

OBJECTIVE: Cisplatin is a widely used, very effective chemotherapeutic agent that can cause severe ototoxicity. In this study, D-methionine was tested as an otoprotectant via round window membrane (RWM) application in the chinchilla. METHODS: A minute amount of cisplatin alone, or D-methionine followed by cisplatin, was applied topically directly to the intact RWM of anesthetized adult chinchillas. Auditory brainstem responses were measured before and 1 week after topical round window application. Animals were killed, and the cochleas were examined. RESULTS: The ears pretreated with D-methionine were completely protected from hearing loss and hair cell loss in the organ of Corti compared with controls. The ears receiving cisplatin without D-methionine protection sustained nearly complete hearing loss with threshold shifts of >60 dB, with extensive outer hair cell loss throughout the organ of Corti but particularly in the basal turn. CONCLUSION: These results demonstrate that topical D-methionine provides excellent otoprotection against cisplatin-induced ototoxicity both electrophysiologically and structurally.