Objectives

Aminoglycoside-induced cochlear ototoxicity causes inner ear hair cells (HCs) loss and leads to hearing impairment in patients, but no treatment completely eliminates the ototoxic effect. This study aims to determine the effectiveness of (−)-Epigallocatechin-3-gallate (EGCG) as a protective agent against aminoglycoside-induced ototoxicity.

Methods

Zebrafish were exposed to EGCG for 24 h and then co-treated with EGCG and ototoxic agent (amikacin and gentamicin) for 5 h to explore the protective effect of EGCG on zebrafish HCs. Network pharmacology analysis and molecular docking simulation were conducted to explore its potential mechanism, and in vitro cell experiments were used to validate the outcome of the result.

Result

EGCG against ototoxicity of aminoglycosides in zebrafish HCs. Network pharmacology analysis and molecular docking showing that molecules related to cellular response regulation to oxidative stress, including AKT1, DHFR, and MET, may be the target proteins of EGCG, which were verified in vitro experiments. Further experiments demonstrated thatEGCG can antagonize the death of HCs caused by amikacin and gentamicin by reducing intracellular reactive oxygen species (ROS) accumulation and anti-apoptosis.

Conclusion

EGCG can be an otoprotective drug against aminoglycosides-induced ototoxicity, prevent cellular apoptosis and significantly reduce oxidative stress.

中文翻译：

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(-)-Epigallocatechin-3-gallate (EGCG) 通过抗氧化和抗凋亡途径防止氨基糖苷类药物引起的耳毒性

目标

氨基糖苷类诱导的耳蜗耳毒性会导致内耳毛细胞 (HCs) 损失并导致患者听力受损，但没有任何治疗可以完全消除耳毒性作用。本研究旨在确定 (-)-Epigallocatechin-3-gallate (EGCG) 作为一种针对氨基糖苷类引起的耳毒性的保护剂的有效性。

方法

将斑马鱼暴露于 EGCG 24 小时，然后与 EGCG 和耳毒性剂（阿米卡星和庆大霉素）共同处理 5 小时，以探索 EGCG 对斑马鱼 HCs 的保护作用。通过网络药理学分析和分子对接模拟探索其潜在机制，并通过体外细胞实验验证结果。

结果

EGCG 对抗斑马鱼 HC 中氨基糖苷类的耳毒性。网络药理学分析和分子对接表明，AKT1、DHFR、MET等与细胞对氧化应激反应调节相关的分子可能是EGCG的靶蛋白，体外实验验证了这一点。进一步的实验表明，EGCG可以通过减少细胞内活性氧（ROS）积累和抗细胞凋亡来拮抗阿米卡星和庆大霉素引起的HCs死亡。

结论

EGCG 是一种耳保护药物，可对抗氨基糖苷类药物引起的耳毒性，防止细胞凋亡并显着降低氧化应激。