Sodium Selenite Acts as an Otoprotectant against Neomycin-Induced Hair Cell Damage in a Zebrafish Model.
Sodium Selenite Acts as an Otoprotectant against Neomycin-Induced Hair Cell Damage in a Zebrafish Model.
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DOI：
10.1371/journal.pone.0151557
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Jung HH
中科院分区：
文献类型：
--
作者：
Chang J;Choi J;Rah YC;Yoo MH;Oh KH;Im GJ;Lee SH;Kwon SY;Park HC;Chae SW;Jung HH
亚硒酸钠是人体多种生理功能所必需的微量元素。它参与了各种生物过程；它作为抗氧化酶的辅助因子，保护免受自由基的侵害，据报道，它可以限制金属介导的DNA氧化损伤。在本研究中，我们研究了亚硒酸钠对野生型和转基因斑马鱼（Brn3C: EGFP）新霉素耳毒性的影响。受精后5或6天，将斑马鱼幼鱼分别暴露于125 μM新霉素和不同浓度（10 μM、100 μM、250 μM和500 μM）亚硒酸钠中1小时。用荧光显微镜分析眼眶上（SO1和SO2）、耳部（O1）和枕部（OC1）侧线神经鞘内的毛细胞（每次处理10条鱼）。毛细胞存活率估计为每组的毛细胞数量与未接触新霉素的对照组的毛细胞数量之比。采用末端脱氧核苷酸转移酶（TdT）介导的dutp -生物素缺口末端标记法（TUNEL）和2-[4-（二甲胺）苯乙烯基]- n -乙基碘化吡啶（DASPEI）法分别评价神经肥大细胞的凋亡和毛细胞损伤。用扫描电镜和透射电镜观察超微结构变化。将125 μM新霉素和500 μM亚硒酸钠分别置于斑马鱼神经肥大毛细胞中保存1 h，亚硒酸钠可防止新霉素诱导的神经肥大毛细胞丢失，减少细胞凋亡，防止斑马鱼超微结构改变。我们提出亚硒酸钠通过抑制细胞凋亡、减少立体纤毛紊乱、防止神经肥大毛细胞超微结构改变来保护斑马鱼免受新霉素诱导的毛细胞损伤。
Sodium selenite is a trace element essential for many physiological functions in the body. It is involved in various biological processes; it acts as a cofactor for antioxidant enzymes that protect against free radicals and is reported to limit metal-mediated oxidative DNA damage. In the present study, we investigated the effect of sodium selenite on neomycin ototoxicity in wild-type and transgenic zebrafish (Brn3C: EGFP). Five or six days post-fertilization, zebrafish larvae were co-exposed to 125 μM neomycin and various concentrations (10 μM, 100 μM, 250 μM, and 500 μM) of sodium selenite for 1 h. Hair cells within neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed by fluorescence microscopy (n = 10 fish per treatment). Hair cell survival was estimated as the ratio of the hair cell numbers in each group compared to those of the control group that were not exposed to neomycin. Apoptosis and hair cell damage of neuromasts were evaluated using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) assay and 2-[4-(dimethylamino) styryl]-N-ethylpyridinium iodide (DASPEI) assay, respectively. Ultrastructural changes were evaluated using scanning electron microscopy and transmission electron microscopy. Neuromast hair cells were preserved in zebrafish exposed to 125 μM neomycin and 500 μM sodium selenite for 1 h. Sodium selenite protected against neomycin-induced hair cell loss of neuromasts, reduced apoptosis, and prevented zebrafish ultrastructural changes. We propose that sodium selenite protects against neomycin-induced hair cell damage by inhibiting apoptosis, decreasing the disarray of stereocilia, and preventing ultrastructural changes in the neuromast hair cells of the zebrafish.