Hong Seok Jin, Im Gi Jung, Chang Jiwon, Chae Sung Won, Lee Seung Hoon, Kwon Soon Young, Jung Hak Hyun, Chung Ah Young, Park Hae Chul, Choi June
Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Ansan-City, South Korea.
Int J Pediatr Otorhinolaryngol. 2013 Jun;77(6):1025-31. doi: 10.1016/j.ijporl.2013.04.003. Epub 2013 Apr 28.
Edaravone is known to have a potent free radical scavenging effect. The objective of the present study was to evaluate the effects of edaravone on cisplatin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP).
Five day post-fertilization zebrafish larvae were exposed to 1000 μM cisplatin and 50 μM, 100 μM, 250 μM, 500 μM, 750 μM, and 1000 μM concentrations of edaravone for 4h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of the hair cells in the control group that were not exposed to cisplatin. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy.
Edaravone protected cisplatin-induced hair cell loss of neuromasts (edaravone 750 μM: 8.7 ± 1.5 cells, cisplatin 1000 μM only: 3.7 ± 0.9 cells; n=10, p<0.0001) and decreased the Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. Structures of mitochondria and hair cell within neuromasts in ultrastructural analysis were preserved in zebrafish exposed to 1000 μM cisplatin and 750 μM edaravone for 4h.
Edaravone attenuated cisplatin-induced hair cell damage in zebrafish. The results of the current study suggest that cisplatin induces apoptosis, and the apoptotic cell death can be prevented by treatment with edaravone in zebrafish.
依达拉奉具有强大的自由基清除作用。本研究的目的是评估依达拉奉对转基因斑马鱼（Brn3C:EGFP）顺铂诱导的耳毒性的影响。
受精后5天的斑马鱼幼虫暴露于1000μM顺铂以及50μM、100μM、250μM、500μM、750μM和1000μM浓度的依达拉奉中4小时。通过荧光显微镜和共聚焦显微镜分析眶上（SO1和SO2）、耳（O1）和枕部（OC1）侧线神经丘内的毛细胞（n=10）。毛细胞存活率以未暴露于顺铂的对照组毛细胞的百分比计算。使用扫描电子显微镜和透射电子显微镜评估超微结构变化。
依达拉奉可保护顺铂诱导的神经丘毛细胞损失（依达拉奉750μM：8.7±1.5个细胞，仅顺铂1000μM：3.7±0.9个细胞；n=10，p<0.0001），并减少末端脱氧核苷酸转移酶（TdT）介导的dUTP生物素缺口末端标记（TUNEL）反应。在暴露于1000μM顺铂和750μM依达拉奉4小时的斑马鱼中，超微结构分析中神经丘内线粒体和毛细胞的结构得以保留。
依达拉奉减轻了斑马鱼顺铂诱导的毛细胞损伤。本研究结果表明顺铂诱导细胞凋亡，而在斑马鱼中用依达拉奉治疗可预防凋亡性细胞死亡。
