Are aminoglycoside antibiotics excitotoxic?
Guinea pigs received gentamicin to induce a profound hearing loss (61 dB auditory threshold shift at 18 kHz). 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.
Sha
S H
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Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
Schacht
J
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005839:Gentamicins / Q000037:antagonists & inhibitors / Q000633:toxicity; D006168:Guinea Pigs; D034381:Hearing Loss / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008298:Maleates / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013644:Tartrates / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D005839:Gentamicins; D008298:Maleates; D016194:Receptors, N-Methyl-D-Aspartate; D013644:Tartrates; C030272:maleic acid; C029768:tartaric acid