Ototoxic interaction of kanamycin and 3-nitropropionic acid.
CONCLUSIONS
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.


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.
Lin
Chia-Der
CD
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
Oshima
Takeshi
T
Oda
Kiyoshi
K
Yamauchi
Daisuke
D
Tsai
Ming-Hsui
MH
Kobayashi
Toshimitsu
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D003292:Convulsants / Q000633:toxicity*; D004347:Drug Interactions; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000473:pathology; D007612:Kanamycin / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D009574:Nitro Compounds / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D003292:Convulsants; D009574:Nitro Compounds; D011422:Propionates; D007612:Kanamycin; C015392:3-nitropropionic acid