Department of Otolaryngology, Head and Neck Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, ROC.
Department of Chinese Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, ROC.
J Chin Med Assoc. 2022 May 1;85(5):617-626. doi: 10.1097/JCMA.0000000000000708. Epub 2022 May 2.
Taxifolin is a flavanonol with efficacious cytoprotective properties, such as anti-inflammatory, antioxidant, anticancer, hepatoprotective, and nephroprotective effects. However, the potential protective effects of taxifolin against gentamicin-induced ototoxicity have not been confirmed. In this study, the possible mechanisms underlying the effects of taxifolin on gentamicin-induced death of UB/OC-2 cochlear cells were investigated.
Mouse cochlear UB/OC-2 cells with or without taxifolin pretreatment were exposed to gentamicin, and the effects on cytotoxicity, reactive oxygen species (ROS) production, mitochondrial permeability transition, and apoptotic marker expression were examined using biochemical techniques, flow cytometry, western blotting, and fluorescent staining.
Little or no apparent effect of taxifolin on cell viability was observed at concentrations less than 40 μM. Further investigations showed that gentamicin significantly inhibited cell viability in a concentration-dependent manner. Pretreatment with taxifolin attenuated gentamicin-induced lactate dehydrogenase release, as well as cellular cytotoxicity. In addition, taxifolin significantly prevented gentamicin-induced cell damage by decreasing ROS production, stabilizing mitochondrial membrane potential, and downregulating the mitochondrial pathway of apoptosis.
In summary, pretreatment with taxifolin is effective for mitigating gentamicin-induced apoptotic cell death mediated by the mitochondrial pathway. Our data suggest that taxifolin provides a new approach to combat gentamicin-induced ototoxicity.
花旗松素是一种具有有效细胞保护特性的黄烷醇，具有抗炎、抗氧化、抗癌、保肝和护肾作用。然而，花旗松素对庆大霉素诱导的耳毒性的潜在保护作用尚未得到证实。在这项研究中，研究了花旗松素对庆大霉素诱导的 UB/OC-2 耳蜗细胞死亡的影响的可能机制。
用或不用花旗松素预处理的小鼠耳蜗 UB/OC-2 细胞暴露于庆大霉素中，并用生化技术、流式细胞术、western blot 和荧光染色来检测对细胞毒性、活性氧（ROS）产生、线粒体通透性转换和凋亡标志物表达的影响。
在浓度低于 40μM 时，花旗松素对细胞活力几乎没有明显影响。进一步的研究表明，庆大霉素以浓度依赖性方式显著抑制细胞活力。用花旗松素预处理可减轻庆大霉素诱导的乳酸脱氢酶释放和细胞毒性。此外，花旗松素通过降低 ROS 产生、稳定线粒体膜电位和下调线粒体凋亡途径，显著防止庆大霉素诱导的细胞损伤。
总之，用花旗松素预处理可有效减轻庆大霉素诱导的线粒体途径介导的凋亡性细胞死亡。我们的数据表明，花旗松素为对抗庆大霉素诱导的耳毒性提供了一种新方法。
