Department of Clinical Laboratory, Taian City Central Hospital, Taian, Shandong, 271000, China.
Department of Obstetrics, Taian City Maternal and Child Health Care Hospital, Taian, Shandong, 271000, China.
Int J Pediatr Otorhinolaryngol. 2021 Nov;150:110920. doi: 10.1016/j.ijporl.2021.110920. Epub 2021 Sep 4.
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.
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.
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.
EGCG can be an otoprotective drug against aminoglycosides-induced ototoxicity, prevent cellular apoptosis and significantly reduce oxidative stress.
氨基糖苷类药物引起的耳蜗毛细胞（HCs）损失导致患者听力受损，但没有一种治疗方法能完全消除耳毒性作用。本研究旨在确定（-）-表没食子儿茶素没食子酸酯（EGCG）作为一种对抗氨基糖苷类药物耳毒性的保护剂的有效性。
将斑马鱼暴露于 EGCG 中 24 小时，然后用 EGCG 和耳毒性药物（阿米卡星和庆大霉素）共同处理 5 小时，以探讨 EGCG 对斑马鱼 HCs 的保护作用。进行网络药理学分析和分子对接模拟，以探讨其潜在机制，并进行体外细胞实验验证结果。
EGCG 对斑马鱼 HCs 的氨基糖苷类耳毒性具有保护作用。网络药理学分析和分子对接表明，与细胞对氧化应激反应调节相关的分子，包括 AKT1、DHFR 和 MET，可能是 EGCG 的靶蛋白，这在体外实验中得到了验证。进一步的实验表明，EGCG 可以通过减少细胞内活性氧（ROS）的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。
EGCG 可以作为一种对抗氨基糖苷类药物引起的耳毒性的耳保护药物，预防细胞凋亡并显著降低氧化应激。
