Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant α-lipoic acid

被引:80
作者
Conlon, BJ
Aran, JM
Erre, JP
Smith, DW
机构
[1] Duke Univ, Med Ctr, Div Otolaryngol Head & Neck Surg, Hearing Res Labs, Durham, NC 27710 USA
[2] Univ Bordeaux 2, Hop Pellegrin, Lab Audiol Expt & Clin, F-33076 Bordeaux, France
关键词
amikacin; aminoglycoside antibiotic; alpha-lipoic acid; dihydrolipoic acid; ototoxicity; free radical; reactive oxygen species; free radical scavenger;
D O I
10.1016/S0378-5955(98)00195-6
中图分类号
R36 [病理学]; R76 [耳鼻咽喉科学];
学科分类号
100104 ; 100213 ;
摘要
Free radical generation is increasingly implicated in a variety of pathological processes, including drug toxicity. Recently, a number of studies have demonstrated the ability of gentamicin to facilitate the generation of radical species both in vivo and in vitro, which suggests that this process plays an important role in aminoglycoside-induced ototoxicity. Free radical scavengers are compounds capable of inactivating free radicals, thereby attenuating their tissue damaging capacity. In this study we have determined the ability of the powerful free radical scavenger alpha-lipoic acid (100 mg/kg/day) to attenuate the cochlear damage induced by a highly ototoxic regimen of the aminoglycoside amikacin (450 mg/kg/day, i.m.). Experiments were carried out on pigmented guinea pigs initially weighing 200-250 g. Changes in cochlear function were characterized as shifts in compound action potential (CAP) thresholds, estimated every 5 days, by use of chronic indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results showed that animals receiving alpha-lipoic acid in combination with amikacin demonstrated a significantly less severe elevation in CAP thresholds compared with animals receiving amikacin alone (P < 0.001; t-test). These results provide further evidence of the recently reported intrinsic role of free radical generation in aminoglycoside ototoxicity, and highlight a potential clinical therapeutic use of alpha-lipoic acid in the management of patients undergoing aminoglycoside treatment. (C) 1999 Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:40 / 44
页数:5
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