Abstract
The use of aminoglycoside antibiotics is limited by ototoxicity that can produce permanent hearing loss. We report that concurrent administration of N-methyl-D-aspartate (NMDA) antagonists markedly attenuates both the hearing loss and destruction of cochlear hair cells in guinea pigs treated with aminoglycoside antibiotics. These findings indicate that aminoglycoside-induced hearing loss is mediated, in part, through an excitotoxic process. The high correlation (Spearman correlation coefficient: 0.928; P < 0.01) obtained between the relative cochleotoxicities of a series of aminoglycosides in humans and the potencies of these compounds to produce a polyamine-like enhancement of [3H]dizocilpine binding to NMDA receptors is consistent with this hypothesis, and provides a simple in vitro assay that can predict this aspect of aminoglycoside-induced ototoxicity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Bacterial Agents / adverse effects*
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Cochlea / pathology
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Dizocilpine Maleate / metabolism
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Dizocilpine Maleate / pharmacology
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Excitatory Amino Acid Antagonists / metabolism
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Excitatory Amino Acid Antagonists / pharmacology*
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Guinea Pigs
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Hair Cells, Auditory
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Hearing Loss / chemically induced
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Hearing Loss / pathology
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Hearing Loss / prevention & control*
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Hearing Tests
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Kanamycin / adverse effects
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Male
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N-Methylaspartate / antagonists & inhibitors*
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Neomycin / adverse effects
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Piperidines / metabolism
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Piperidines / pharmacology
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Prosencephalon
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate / metabolism
Substances
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Anti-Bacterial Agents
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Excitatory Amino Acid Antagonists
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Piperidines
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Receptors, N-Methyl-D-Aspartate
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Kanamycin
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N-Methylaspartate
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Dizocilpine Maleate
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Neomycin
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ifenprodil