Jie Ni1, Hongye Wang2, Xiyi Wei2,3, Kangjie Shen2, Yeqin Sha2, Yuxiang Dong2, Yimei Shu2, Xiaojie Wan4, Jingwen Cheng5, Fang Wang6, Yihai Liu7. 1. Department of Emergency, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China. 2. The First Clinical Medical School, Nanjing Medical University, Nanjing, China. 3. Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 4. Clinical School of Imaging, Nanjing Medical University, Nanjing, China. 5. The Medical School of Pediatrics, Nanjing Medical University, Nanjing, China. 6. Department of Emergency, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, Jiangsu Province, China. 771647652@qq.com. 7. Department of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China. drhai@njmu.edu.cn.
Abstract
BACKGROUND: The cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism is unclear. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: The cardiotoxicity of isoniazid on zebrafish embryos and its underlying mechanism is unclear. METHODS: 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. RESULTS: 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. CONCLUSION: 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.