International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, China; Institute for Marine Biosystem and Neuroscience, International Center for Marine Studies, Shanghai Ocean University, Shanghai, China.
International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, China; Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Ministry of Education, Shanghai Ocean University, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2021 Sep;247:109053. doi: 10.1016/j.cbpc.2021.109053. Epub 2021 Apr 19.
Ototoxicity of drugs is an important inducement for hearing loss. Anisomycin is a candidate drug for parasite, cancer, immunosuppression, and mental disease. However, the ototoxicity of anisomycin has not been examined. In this study, the ototoxicity of anisomycin was evaluated using zebrafish lateral line. We found the zebrafish treated with anisomycin during lateral line development could inhibit hair cell formation in a time- and dose-dependent manner. After neuromasts are mature with differentiated hair cells by 5 day post-fertilization, anisomycin could induce hair cell loss effectively through chronic exposure rather than acute exposure. TUNEL assay and qPCR of apoptosis related genes tp53, casp8, casp3a, and casp3b indicated that cell apoptotic was induced by chronic anisomycin exposure. Furthermore, knocking down tp53 with antisense morpholino could attenuate the hair cell loss induced by anisomycin. In addition, we found that anisomycin chronic exposure also inhibited the proliferation of supporting cell. Together, these results indicate that chronic anisomycin exposure could induce hair cell death and block supporting cell proliferation, which causes hair cell loss in zebrafish neuromast. This study provides primary ototoxicity evaluation for anisomycin.
药物的耳毒性是导致听力损失的一个重要因素。放线菌酮是一种候选药物，可用于寄生虫、癌症、免疫抑制和精神疾病的治疗。然而，放线菌酮的耳毒性尚未被研究过。在这项研究中，我们使用斑马鱼侧线评估了放线菌酮的耳毒性。我们发现，在斑马鱼侧线发育过程中用放线菌酮处理，可呈时间和剂量依赖性抑制毛细胞的形成。在 5 天孵化后，感觉上皮的毛细胞分化成熟后，通过慢性暴露而非急性暴露，放线菌酮可以有效地诱导毛细胞丧失。TUNEL 检测和细胞凋亡相关基因 tp53、casp8、casp3a 和 casp3b 的 qPCR 表明，慢性放线菌酮暴露诱导了细胞凋亡。此外，用反义 morpholino 敲低 tp53 可以减轻放线菌酮引起的毛细胞丧失。此外，我们发现放线菌酮慢性暴露还抑制了支持细胞的增殖。综上所述，这些结果表明，慢性放线菌酮暴露可诱导毛细胞死亡和阻断支持细胞增殖，从而导致斑马鱼感觉上皮毛细胞丧失。这项研究为放线菌酮的初步耳毒性评估提供了依据。
