Round Window Application of D‐Methionine Provides Complete Cisplatin Otoprotection

• DOI: 10.1067/mhn.2002.125299
• Publication Date: 2003-02-05T02:49:09Z
• Authors: Kurtis D. Korver; Leonard P. Rybak; Craig Whitworth; Kathleen M. Campbell
• Keywords: Male; Administration, Topical; Hearing Loss, Sensorineural; Auditory Threshold; Sensitivity and Specificity; Cochlea; Disease Models, Animal; 03 medical and health sciences; Methionine; 0302 clinical medicine; Audiometry; Round Window, Ear; Chinchilla; Reference Values; Animals; Drug Interactions; Female; Cisplatin

OBJECTIVECisplatin 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.METHODSA 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.RESULTSThe 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.CONCLUSIONThese results demonstrate that topical D‐methionine provides excellent otoprotection against cisplatin‐induced ototoxicity both electrophysiologically and structurally.