Hirose Yoshinobu, Sugahara Kazuma, Kanagawa Eiju, Takemoto Yousuke, Hashimoto Makoto, Yamashita Hiroshi
Department of Otolaryngology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Department of Otolaryngology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Hear Res. 2016 Dec;342:80-85. doi: 10.1016/j.heares.2016.10.001. Epub 2016 Oct 4.
Eighteen supplement drugs were screened using hair cells to determine a protective effect against the adverse effects of neomycin by using the zebrafish lateral line. The zebrafish were administered the supplement drugs 1 h before neomycin exposure. One hour later, animals were fixed in paraformaldehyde. Dose-response curves were generated to evaluate the protective effect on hair cells. The screen identified 3 supplements (quercetin, catechin and tannic acid). Three minutes after exposure to neomycin, increased antioxidant activity was found in the lateral line hair cells, as determined by the analysis of oxidative stress. Quercetin decreases antioxidant activity. The identified drugs were also investigated to determine whether they protect the cochlea against noise-induced hearing loss in guinea pigs. The drugs were administered via the intraperitoneal route in the guinea pigs 3 days before and 4 days after noise exposure. Seven days after noise exposure (130-dB sound pressure level for 3 h), the auditory brainstem response threshold shifts were assessed. We observed that the auditory brainstem response threshold shift was significantly less in the quercetin group than in the vehicle control group. The results of our study indicate that screening drugs using zebrafish can determine additional protective drugs for the inner ear.
使用毛细胞筛选了18种补充剂药物，通过斑马鱼侧线来确定其对新霉素不良反应的保护作用。在暴露于新霉素前1小时给斑马鱼施用补充剂药物。1小时后，将动物固定在多聚甲醛中。生成剂量反应曲线以评估对毛细胞的保护作用。筛选确定了3种补充剂（槲皮素、儿茶素和单宁酸）。通过氧化应激分析确定，在暴露于新霉素3分钟后，侧线毛细胞中的抗氧化活性增加。槲皮素会降低抗氧化活性。还对鉴定出的药物进行了研究，以确定它们是否能保护豚鼠的耳蜗免受噪声引起的听力损失。在噪声暴露前3天和暴露后4天，通过腹腔途径给豚鼠施用这些药物。在噪声暴露7天后（130分贝声压级，持续3小时），评估听觉脑干反应阈值的变化。我们观察到，槲皮素组的听觉脑干反应阈值变化明显小于载体对照组。我们研究结果表明，利用斑马鱼筛选药物可以确定其他对内耳有保护作用的药物。
