Round window application of D-methionine provides complete cisplatin otoprotection

Otolaryngol Head Neck Surg. 2002 Jun;126(6):683-9. doi: 10.1067/mhn.2002.125299.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Topical
  • Animals
  • Audiometry
  • Auditory Threshold
  • Chinchilla
  • Cisplatin / adverse effects*
  • Cochlea / drug effects
  • Cochlea / pathology*
  • Disease Models, Animal
  • Drug Interactions
  • Female
  • Hearing Loss, Sensorineural / chemically induced*
  • Hearing Loss, Sensorineural / prevention & control*
  • Male
  • Methionine / pharmacology*
  • Reference Values
  • Round Window, Ear / drug effects*
  • Round Window, Ear / pathology
  • Sensitivity and Specificity

Substances

  • Methionine
  • Cisplatin