N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss
N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss
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DOI：
10.1038/nm1296-1338
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发表时间：
1996-12-01
期刊：
影响因子：
82.9
通讯作者：
Skolnick, P
中科院分区：
文献类型：
--
作者：
Basile, AS;Huang, JM;Skolnick, P
氨基糖苷类抗生素的使用受到耳毒性的限制，这种毒性可能会导致永久性听力损失。我们报告同时给予N-甲基-D-天冬氨酸(NMDA)拮抗剂显著减轻氨基糖苷类抗生素治疗的豚鼠的听力损失和耳蜗毛细胞的破坏。这些发现表明，氨基糖苷类药物引起的听力损失部分是通过兴奋性毒性过程来调节的。一系列氨基糖苷类化合物在人体内的相对耳毒性与这些化合物产生多胺样增强[H-3]地佐西平与N-甲基-D-天冬氨酸受体结合的能力之间的高度相关性(Spearman相关系数：0.928；P<0.01)与这一假设是一致的，并提供了一种简单的体外试验来预测氨基糖苷类药物所致耳毒性的这一方面。
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 [H-3]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.