Round window application of D-methionine provides complete cisplatin otoprotection.

Abstract

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. 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. 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. These results demonstrate that topical D-methionine provides excellent otoprotection against cisplatin-induced ototoxicity both electrophysiologically and structurally.