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优化鼓室内注射 N-乙酰半胱氨酸浓度以预防豚鼠顺铂耳毒性

Optimal N-acetylcysteine concentration for intratympanic injection to prevent cisplatin-induced ototoxicity in guinea pigs.

机构信息

Department of Otolaryngology, Hualien Tzu Chi Hospital, Medical Foundation, Hualien, Taiwan.

Department of otolaryngology Head and Neck Surgery, School of Medicine, Chi University, Hualien, Taiwan.

出版信息

Acta Otolaryngol. 2022 Feb;142(2):127-131. doi: 10.1080/00016489.2022.2038796. Epub 2022 Mar 15.

Abstract

BACKGROUND

Cisplatin is a chemotherapy drug that can induce sensorineural hearing loss. At present, no otoprotective agent is approved for use.

OBJECTIVES

This study investigated the optimal concentration of intratympanic N-acetylcysteine (NAC) to prevent cisplatin-induced ototoxicity in a guinea pig model.

MATERIALS AND METHODS

Guinea pigs ( = 64) were treated with a single intratympanic injection containing different NAC concentrations or saline (control) 3 days prior to intraperitoneal injection with cisplatin. The threshold change in the auditory brainstem response was assessed.

RESULTS

Four weeks after intraperitoneal cisplatin injection, only the group that received 2% NAC exhibited significant otoprotection ( < .05) compared with the control. Otoprotection was observed at all the frequencies tested (1k, 2k, 4k, and 8k Hz). The 2% NAC group also exhibited significant otoprotection ( < .05) compared with the other NAC groups (at 1k, 2k, 4k, and 8k Hz). The 4% NAC group exhibited significantly reduced hearing capacity ( < .05) in the fourth week compared with controls.

CONCLUSIONS AND SIGNIFICANCE

Intratympanic NAC administration is an efficient and safe means of preventing cisplatin-induced ototoxicity. In our animal model, the optimal intratympanic NAC concentration was 2%; concentrations of 4% loss of otoprotection.

摘要

背景

顺铂是一种化疗药物,可引起感音神经性听力损失。目前,尚无批准用于预防顺铂耳毒性的耳保护剂。

目的

本研究旨在探讨鼓室内给予 N-乙酰半胱氨酸(NAC)的最佳浓度,以预防豚鼠模型中顺铂诱导的耳毒性。

材料和方法

豚鼠( = 64)在腹腔注射顺铂前 3 天接受不同 NAC 浓度的鼓室内注射或生理盐水(对照)治疗。评估听觉脑干反应的阈值变化。

结果

腹腔注射顺铂 4 周后,仅接受 2% NAC 治疗的组与对照组相比表现出显著的耳保护作用( < .05)。在所有测试频率(1k、2k、4k 和 8k Hz)均观察到耳保护作用。与其他 NAC 组相比(在 1k、2k、4k 和 8k Hz),2% NAC 组也表现出显著的耳保护作用( < .05)。与对照组相比,4% NAC 组在第 4 周时听力明显下降( < .05)。

结论和意义

鼓室内给予 NAC 是预防顺铂诱导的耳毒性的有效且安全的方法。在我们的动物模型中,最佳的鼓室内 NAC 浓度为 2%;浓度为 4%则失去耳保护作用。

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