Park Moo Kyun, Im Gi Jung, Chang Jiwon, Chae Sung Won, Yoo Jun, Han Won-gue, Hwang Gyu Ho, Jung Jong Yoon, Choi Jungim, Jung Hak Hyun, Chung Ah-Young, Park Hae-Chul, Choi June
Department of Otolaryngology - Head and Neck Surgery, Seoul National University College of Medicine, Seoul, South Korea.
Department of Otorhinolaryngology - Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.
Int J Pediatr Otorhinolaryngol. 2014 Aug;78(8):1311-5. doi: 10.1016/j.ijporl.2014.05.018. Epub 2014 May 24.
Caffeic acid phenethyl ester (CAPE) is known to reduce the generation of oxygen-derived free radicals, which is a major mechanism of aminoglycoside-induced ototoxicity. The objective of the present study was to evaluate the effects of CAPE on neomycin-induced ototoxicity in zebrafish (Brn3c: EGFP).
Five-day post-fertilization zebrafish larvae (n=10) were exposed to 125 μM neomycin and one of the following CAPE concentrations for 1h: 50, 100, 250, 500, or 1000 μM. Ultrastructural changes were evaluated using scanning electron microscopy (SEM). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) assay and 2-[4-(dimethylamino)styryl]-N-ethylpyridiniumiodide (DASPEI) assay were performed for evaluation of apoptosis and mitochondrial damage.
CAPE decreased neomycin-induced hair cell loss in the neuromasts (500 μM CAPE: 12.7 ± 1.1 cells, 125 μM neomycin only: 6.3 ± 1.1 cells; n = 10, P < 0.05). In the ultrastructural analysis, structures of mitochondria and hair cells were preserved when exposed to 125 μM neomycin and 500 μM CAPE. CAPE decreased apoptosis and mitochondrial damage.
In the present study, CAPE attenuated neomycin-induced hair cell damage in zebrafish. The results of the current study suggest that neomycin induces apoptosis, and the apoptotic cell death can be prevented by treatment with CAPE in zebrafish.
已知咖啡酸苯乙酯（CAPE）可减少氧衍生自由基的产生，这是氨基糖苷类药物引起耳毒性的主要机制。本研究的目的是评估CAPE对斑马鱼（Brn3c：EGFP）新霉素诱导的耳毒性的影响。
将受精后5天的斑马鱼幼虫（n = 10）暴露于125μM新霉素和以下CAPE浓度之一1小时：50、100、250、500或1000μM。使用扫描电子显微镜（SEM）评估超微结构变化。进行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）分析和2-[4-（二甲基氨基）苯乙烯基]-N-乙基碘化吡啶（DASPEI）分析，以评估细胞凋亡和线粒体损伤。
CAPE减少了新霉素诱导的神经丘毛细胞损失（500μM CAPE：12.7±1.1个细胞，仅125μM新霉素：6.3±1.1个细胞；n = 10，P <0.05）。在超微结构分析中，当暴露于125μM新霉素和500μM CAPE时，线粒体和毛细胞的结构得以保留。CAPE减少了细胞凋亡和线粒体损伤。
在本研究中，CAPE减轻了新霉素诱导的斑马鱼毛细胞损伤。当前研究结果表明新霉素诱导细胞凋亡，而在斑马鱼中用CAPE治疗可预防凋亡性细胞死亡。
