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

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 (n = 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 (p < .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 (p < .05) compared with the other NAC groups (at 1k, 2k, 4k, and 8k Hz). The 4% NAC group exhibited significantly reduced hearing capacity (p < .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.

Chinese Abstract

背景：顺铂是一种可诱发感音神经性听力损失的化疗药物。目前还没有任何耳保护剂获准使用。

目的：本研究调查了对于豚鼠模型, 防止顺铂诱发的耳毒性的鼓室内 N-乙酰半胱氨酸 (NAC) 的最佳浓度。

材料和方法：豚鼠（n = 64）在腹腔注射顺铂 3 天之前, 用含有不同 NAC 浓度或盐水（对照）进行单次鼓室注射治疗。评估了听觉脑干反应的阈值变化。

结果：腹腔内顺铂注射 4 周后, 与对照组相比, 只有接受 2% NAC 的组表现出显著的耳保护作用 (p < .05)。在所有测试的频率（1k、2k、4k 和 8k Hz）都观察到耳保护作用。与其他 NAC 组（1k、2k、4k 和 8k Hz）相比, 2% NAC 组也表现出显著的耳保护作用（p < .05）。 4% NAC 组与对照组相比, 第四周的听力能力显著降低 (p < .05)。

结论和意义：鼓室内 NAC 治疗是一种有效和安全的防止顺铂引起耳毒性的方法。在我们的动物模型中, 最佳鼓室内 NAC 浓度为 2%；浓度为 4% , 耳保护作用丧失。

Keywords:

• Cisplatin chemotherapy
• ototoxicity
• intratympanic injection

Acknowledgements

The authors thank for the useful suggestions and comments from reviewers. The manuscript was English edited by Wallace Academic Editing.

Disclosure statement

The authors declare no conflict of interest

Additional information

Funding

This study was supported by grant NSC 98-2314-B-303003-MY3 from the National Science Council, R.O.C. (Taiwan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.