Conlon B J, Smith D W
Hearing Research Laboratories, Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Acta Otolaryngol. 2000 Aug;120(5):596-9. doi: 10.1080/000164800750000397.
Cochlear damage following topical application of aminoglycoside antibiotics to the round window membrane is a recognized phenomenon in both animal experiments and clinical reports. The authors have recently reported the ability of the free radical scavenging agent, alpha lipoic acid, to protect against the cochleo-toxic side effects of systemically administered aminoglycoside antibiotics. This study attempts to determine if the protective effect of this free radical scavenging agent is also seen following topical aminoglycoside application. Animals were implanted with osmotic pumps which delivered 2.5 microl/h solution of either neomycin 5% or neomycin plus alpha lipoic acid (50 mg/ml). Control animals received normal saline solution. Drug solutions were presented directly to the round window membrane over a 7-day period. Auditory sensitivity was monitored using compound action potentials (CAPs) of the auditory nerve recorded through an implanted chronic electrode terminating at the round window. Sixteen animals were entered into the study and randomized to one of the above groups. All animals receiving neomycin solution, with or without alpha lipoic acid, maintained normal thresholds for the first 3 days of the treatment period. Animals receiving neomycin solution alone experienced profound and rapid deterioration in auditory sensitivity, which was maximal by day 6. Animals receiving neomycin plus alpha lipoic acid also experienced significant cochlear damage; however, the rate of deterioration was slower than that seen in the group receiving neomycin alone. All control animals receiving saline maintained good hearing thresholds throughout the treatment period.
在动物实验和临床报告中，向圆窗膜局部应用氨基糖苷类抗生素后出现耳蜗损伤是一种公认的现象。作者最近报告了自由基清除剂α硫辛酸能够预防全身应用氨基糖苷类抗生素产生的耳蜗毒性副作用。本研究旨在确定局部应用氨基糖苷类抗生素后是否也能观察到这种自由基清除剂的保护作用。给动物植入渗透泵，其能以2.5微升/小时的速度输送5%新霉素溶液或新霉素加α硫辛酸（50毫克/毫升）溶液。对照动物接受生理盐水溶液。在7天时间内将药物溶液直接施用于圆窗膜。通过植入在圆窗处的慢性电极记录听神经的复合动作电位（CAPs）来监测听觉敏感性。16只动物进入该研究并随机分为上述组之一。所有接受新霉素溶液（无论是否添加α硫辛酸）的动物在治疗期的前3天维持正常阈值。单独接受新霉素溶液的动物听觉敏感性出现严重且迅速的恶化，在第6天时达到最大程度。接受新霉素加α硫辛酸的动物也出现了明显的耳蜗损伤；然而，其恶化速度比单独接受新霉素的组要慢。所有接受生理盐水的对照动物在整个治疗期都保持良好的听力阈值。
