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褪黑素减轻新霉素诱导的斑马鱼毛细胞损伤。

Melatonin mitigates neomycin-induced hair cell injury in zebrafish.

作者信息

Oh Kyoung Ho, Rah Yoon Chan, Hwang Kyu Ho, Lee Seung Hoon, Kwon Soon Young, Cha Jae Hyung, Choi June

机构信息

a Department of Otorhinolaryngology-Head and Neck Surgery , Korea University College of Medicine , Seoul , South Korea and.

b Medical Science Research Center, Korea University College of Medicine , Ansan , South Korea.

出版信息

Drug Chem Toxicol. 2017 Oct;40(4):390-396. doi: 10.1080/01480545.2016.1244679. Epub 2016 Nov 18.

Abstract

CONTEXT

Ototoxicity due to medications, such as aminoglycosides, is irreversible, and free radicals in the inner ear are assumed to play a major role. Because melatonin has an antioxidant property, we hypothesize that it might mitigate hair cell injury by aminoglycosides.

OBJECTIVE

The objective of this study was to evaluate whether melatonin has an alleviative effect on neomycin-induced hair cell injury in zebrafish (Danio rerio).

METHODS

Various concentrations of melatonin were administered to 5-day post-fertilization zebrafish treated with 125 μM neomycin for 1 h. Surviving hair cells within four neuromasts were compared with that of a control group. Apoptosis was assessed via terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. The changes of ultrastructure were confirmed using a scanning electron microscope.

RESULTS

Melatonin alleviated neomycin-induced hair cell injury in neuromasts (neomycin + melatonin 100 μM: 13.88 ± 0.91 cells, neomycin only: 7.85 ± 0.90 cells; n = 10, p < 0.05) and reduced neomycin-induced apoptosis in the TUNEL assay. In ultrastructural analysis, hair cells within the neuromasts in zebrafish were preserved exposed to 125 μM neomycin and 100 μM melatonin for 1 h in SEM findings.

CONCLUSION

Melatonin is effective in alleviating aminoglycoside-induced hair cell injury in zebrafish. The results of this study demonstrated that melatonin has the potential to reduce apoptosis induced by aminoglycosides in zebrafish.

摘要

背景

药物(如氨基糖苷类)引起的耳毒性是不可逆的,内耳中的自由基被认为起主要作用。由于褪黑素具有抗氧化特性,我们推测它可能减轻氨基糖苷类药物对毛细胞的损伤。

目的

本研究的目的是评估褪黑素对新霉素诱导的斑马鱼(Danio rerio)毛细胞损伤是否具有缓解作用。

方法

将不同浓度的褪黑素施用于受精后5天、用125μM新霉素处理1小时的斑马鱼。比较四个神经丘内存活的毛细胞与对照组的情况。通过末端脱氧核苷酸转移酶dUTP缺口末端标记法评估细胞凋亡。使用扫描电子显微镜确认超微结构的变化。

结果

褪黑素减轻了新霉素诱导的神经丘毛细胞损伤(新霉素+100μM褪黑素:13.88±0.91个细胞,仅新霉素组:7.85±0.90个细胞;n = 10,p < 0.05),并在TUNEL试验中减少了新霉素诱导的细胞凋亡。在超微结构分析中,扫描电子显微镜结果显示,斑马鱼神经丘内的毛细胞在暴露于125μM新霉素和100μM褪黑素1小时后得以保留。

结论

褪黑素可有效减轻斑马鱼中氨基糖苷类药物诱导的毛细胞损伤。本研究结果表明,褪黑素具有减少斑马鱼中氨基糖苷类药物诱导的细胞凋亡的潜力。

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