Cisplatin Ototoxicity in the Guinea Pig: An Electrophysiological, Morphological, and Biochemical Study

The purpose of this study was to determine changes induced by cisplatin on hair cell (HC) morphology, compound action potential (CAP), Preyer reflex (PR), and Na,K-ATPase activity in the cochlear lateral wall. Guinea pigs were treated with either 0.42, 0.83, 1.17, 1.50 mg/kg cisplatin, i.p. or sterile water for 12 consecutive days and tested on day 13. HC condition was visualized with scanning electron microscopy (SEM), CAP was initiated with a 1 volt click, and Na,K-ATPase activity was measured by the method of Fiske and SubbaRow. HC damage was linear with dose and occurred throughout the turns of the cochlea with greatest predominance in the basal turn. Degrees of HC distortion were represented by separation of stereocilia, formation of blebs, and expulsion of HC contents. Complete suppression of CAP and PR occurred in all 1.5 mg/kg treated animals and 50% of the 1.17 mg/kg dose group. A 60% depression of CAP occurred in 50% of the 0.83 dose group. Na,K-ATPase activity was not significantly different between treatment groups. These results indicated that cisplatin ototoxicity appeared to be dose-dependent for measurements of CAP, PR and HC damage but was not related to Na,K-ATPase activity in cochlear lateral wall