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


CONCLUSIONS
These results demonstrate that topical D-methionine provides excellent otoprotection against cisplatin-induced ototoxicity both electrophysiologically and structurally.
Korver
Kurtis D
KD
Division of Otolaryngology, Southern Illinois University, Springfield, USA.
Rybak
Leonard P
LP
Whitworth
Craig
C
Campbell
Kathleen M
KM
D000287:Administration, Topical; D000818:Animals; D001299:Audiometry; D001309:Auditory Threshold; D002682:Chinchilla; D002945:Cisplatin / Q000009:adverse effects*; D003051:Cochlea / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D012016:Reference Values; D012405:Round Window, Ear / Q000187:drug effects* / Q000473:pathology; D012680:Sensitivity and Specificity
D008715:Methionine; D002945:Cisplatin