Galangin prevents aminoglycoside-induced ototoxicity by decreasing mitochondrial production of reactive oxygen species in mouse cochlear cultures
Galangin prevents aminoglycoside-induced ototoxicity by decreasing mitochondrial production of reactive oxygen species in mouse cochlear cultures
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DOI：
10.1016/j.toxlet.2016.01.005
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发表时间：
2016-03-14
影响因子：
3.5
通讯作者：
Lee, Kyu-Yup
中科院分区：
文献类型：
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作者：
Kim, Ye-Ri;Kim, Min-A;Lee, Kyu-Yup
阿米卡星是一种半合成的氨基糖苷类抗生素，广泛用于治疗由耐庆大霉素的革兰氏阴性菌和非结核分枝杆菌引起的感染。然而，由于活性氧（ROS）的过度产生，使用这种药物通常会导致耳毒性。高良姜素是一种天然的黄酮类化合物，通过减少线粒体活性氧的产生，对线粒体功能障碍具有保护作用。免疫荧光染色显示高良姜素处理的内毛细胞（IHC）和外毛细胞（OHC）显着减少阿米卡星引起的损害。此外，用高良姜素预处理导致减少阿米卡星引起的两种类型的毛细胞中的ROS产生的增加，通过MitoSOX-红染色。用活性caspase-3抗体和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）法检测细胞凋亡，并与单独阿米卡星组比较（P < 0.05）。这些结果表明，高良姜素保护Corti器官中的毛细胞从阿米卡星诱导的毒性，通过减少线粒体ROS的产生。本研究的结果表明，高良姜素可以潜在地被用作抗氧化剂和抗凋亡剂，以防止由氨基糖苷类诱导的氧化应激引起的听力损失。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Amikacin is a semi-synthetic aminoglycoside widely used to treat infections caused by gentamicin-resistant gram-negative organisms and nontuberculous mycobacteria. However, the use of this agent often results in ototoxicity due to the overproduction of reactive oxygen species (ROS). Galangin, a natural flavonoid, has been shown to play a protective role against mitochondrial dysfunction by reducing mitochondrial ROS production.In this study, the effect of galangin on amikacin-induced ototoxicity was examined using cultures of cochlear explants. Immunofluorescent staining showed that treatment of inner hair cells (IHCs) and outer hair cells (OHCs) with galangin significantly decreased damage induced by amikacin. Moreover, pretreatment with galangin resulted in decreased amikacin-provoked increase in ROS production in both types of hair cells by MitoSOX-red staining. Attenuation of apoptotic cell death was assessed immunohistochemically using active caspase-3 antibody and with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, compared to explants exposed to amikacin alone (P < 0.05). These results indicate that galangin protects hair cells in the organ of Corti from amikacin-induced toxicity by reducing the production of mitochondrial ROS.The results of this study suggest that galangin can potentially be used as an antioxidant and antiapoptotic agent to prevent hearing loss caused by aminoglycoside induced-oxidative stress. (C) 2016 Elsevier Ireland Ltd. All rights reserved.