Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
Environ Toxicol. 2023 Mar;38(3):604-614. doi: 10.1002/tox.23707. Epub 2022 Nov 11.
Ototoxicity refers to damage of sensory hair cells and functional hearing impairment following aminoglycosides exposure. Previously, we have determined that ferulic acid (FA) protected hair cells against serial concentrations of neomycin-induced ototoxic damage. The aim of the present study is to assess the mechanism and effects of FA on neomycin-induced hair cells loss and impact on mechanosensory-mediated behaviors alteration using transgenic zebrafish (pvalb3b: TagGFP). We first identified the optimal protective condition as pre/co-treatment method in early fish development. Pretreatment of the larvae with FA significantly protected against neomycin-induced hair cells loss through preventing neomycin passed through the cytoplasm of hair cells, and subsequently decreased reactive oxygen species production and TUNEL signals in 4 day post-fertilization (dpf) transgenic zebrafish larvae. Moreover, preservation of functional hair cells correlated directly with rescue of the altered swimming behavior, indicates FA pretreatment protects against neomycin ototoxic damage in 7-dpf transgenic zebrafish larvae. Together, our findings unravel the otoprotective role of FA as an effective agent against neomycin-induced ototoxic effects and offering the theoretical foundation for discovering novel candidates for hearing protection.
耳毒性是指氨基糖苷类药物暴露后感觉毛细胞的损伤和功能听力障碍。以前，我们已经确定阿魏酸（FA）可保护毛细胞免受新霉素诱导的耳毒性损伤的连续浓度影响。本研究旨在评估 FA 对新霉素诱导的毛细胞损失的作用机制及其对机械感觉介导的行为改变的影响，使用转基因斑马鱼（pvalb3b:TagGFP）。我们首先确定了最佳的保护条件作为早期鱼类发育中的预处理/共处理方法。FA 的预处理可通过防止新霉素穿过毛细胞的细胞质来显著防止新霉素诱导的毛细胞损失，并随后减少 4 天受精后（dpf）转基因斑马鱼幼虫中的活性氧产生和 TUNEL 信号。此外，功能毛细胞的保存与游泳行为改变的挽救直接相关，表明 FA 预处理可防止 7 天受精后转基因斑马鱼幼虫的新霉素耳毒性损伤。总之，我们的研究结果揭示了 FA 的耳保护作用，FA 作为一种有效对抗新霉素耳毒性作用的药物，为发现新的听力保护候选药物提供了理论基础。
