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Are aminoglycoside antibiotics excitotoxic?

Sha, Su-Hua1; Schacht, Jochen1,2

Auditory and Vestibular Systems, Lateral Line
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GUINEA pigs received gentamicin to induce a profound hearing loss (61 dB auditory threshold shift at 18kHz). Concomitant administration of maleic or tartaric acid dissolved in dimethyl sulfoxide (DMSO) significantly reduced the threshold shift to< 40 dB. The results have several important implications. First, they support the hypothesis of a free-radical mechanism of gentamicin toxicity since the protective compounds are metal chelators and scavengers. Second, they caution against these and similar chemicals, commonly found in drug preparations, as vehicles in tests of aminoglycoside toxicity. For example, a recent study by others describing attenuation of aminoglycoside ototoxicity by NMDA antagonists may have been influenced by the presence of maleate, tartrate and DMSO. Third, they suggest simple antioxidants as a potentially efficient and inexpensive clinical prophylaxis of aminoglycoside-induced hearing loss.

1Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506, USA

2Corresponding Author: Jochen Schacht

ACKNOWLEDGEMENTS: This research was supported by research grant DC-03685 from the National Institutes for Deafness and Communication Disorders and a REAP grant from the Office of Dietary Supplements, National Institutes of Health.

Received 26 August 1998; accepted 23 September 1998

© 1998 Lippincott Williams & Wilkins, Inc.