Ototoxic interaction of kanamycin and 3-nitropropionic acid.

CONCLUSION: Mitochondrial dysfunction in the cochlea potentiates the ototoxicity of aminoglycosides. OBJECTIVE: This study examined whether mitochondrial dysfunction in the cochlea affects the ototoxicity of aminoglycosides. MATERIALS AND METHODS: Nineteen guinea pigs were treated with the mitochondrial toxin 3-nitropropionic acid (3-NP), kanamycin, both agents, or normal saline as control. After 14 days, hair cell loss and auditory brainstem response (ABR) were assessed. RESULTS: The administration of 400 mg/kg of kanamycin caused neither hair cell loss nor ABR threshold shift. Administration of 3-NP caused mild ABR threshold shift without significant hair cell loss. Administration of 3-NP and kanamycin caused ABR threshold shift and significant hair cell loss.