Experimental model of cisplatin ototoxicity in chinchillas

Cisplatin is an important antineoplastic agent, Its ototoxicity has been we ll defined, both in human and animal studies. However, animal models of sys temic cisplatin administration have been complicated by multiple toxic effe cts. We studied cisplatin ototoxicity in an animal model involving topical application of cisplatin to the round-window membrane. Adult chinchillas we re anesthetized with ketamine and pentobarbital, and auditory function was tested with the use of auditory brain-stem responses to various stimuli (cl icks and 8-and 16-kHz tone bursts). Each animal was used as its own control . The middle-ear cavity was exposed through the bulla. In the experimental ear, a 25-mu l solution of 0.25 mg cisplatin/1.0 mi normal saline solution was applied to the round-window membrane, In the control ear, 25 mu l norma l saline solution was applied to the round-window membrane, Follow-up audit ory brain-stem response testing was conducted 7 days after treatment. A sig nificant increase in threshold in the experimental ears was seen on compari son with the control ears, This finding suggests that application of cispla tin to the round-window membrane is a useful animal model in which to study cisplatin ototoxicity.