The cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism is unclear. Here, we exposed zebrafish embryos at 4 h post-fertilization to different levels of isoniazid and recorded the morphology and number of malformed and dead embryos under the microscope. The high concentration of isoniazid group showed more malformed and dead embryos than the low concentration of isoniazid group and control group. The morphology of the heart and its alteration were visualized using transgenic zebrafish (cmlc2: GFP) and confirmed by in situ hybridization. The negative effects of isoniazid on the developing heart were characterized by lower heart rate and more heart looping disorders. Mechanistically, PCR showed decreased expression of heart-specific transcription factors when exposed to isoniazid. Oxidative stress was induced by isoniazid in cardiomyocytes, mediated by decreased activities of catalase and superoxide dismutase, which were rescued by scavengers of reactive oxygen species. In conclusion, this study demonstrated that isoniazid led to heart looping disturbance by the downregulation of cardiac-specific transcription factors and induction of cardiomyocyte apoptosis.

中文翻译：

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异烟肼通过诱导氧化应激导致斑马鱼胚胎心循环障碍


异烟肼对斑马鱼胚胎的心脏毒性及其潜在机制尚不清楚。在这里，我们将受精后 4 小时的斑马鱼胚胎暴露于不同水平的异烟肼中，并在显微镜下记录畸形和死亡胚胎的形态和数量。高浓度异烟肼组比低浓度异烟肼组和对照组出现更多的畸形和死亡胚胎。使用转基因斑马鱼（cmlc2：GFP）观察心脏的形态及其变化，并通过原位杂交进行确认。异烟肼对发育中的心脏的负面影响的特点是心率降低和更多的心循环障碍。从机制上讲，PCR 显示，当暴露于异烟肼时，心脏特异性转录因子的表达降低。异烟肼在心肌细胞中诱导氧化应激，介导的过氧化氢酶和超氧化物歧化酶活性降低，而活性氧清除剂可挽救氧化应激。总之，本研究证明异烟肼通过下调心脏特异性转录因子并诱导心肌细胞凋亡而导致心脏循环障碍。