Melatonin Prevents NaAsO<sub>2</sub>-Induced Developmental Cardiotoxicity in Zebrafish through Regulating Oxidative Stress and Apoptosis
Rui Yan,
Jie Ding,
Yuanjie Wei,
Qianlei Yang,
Xiaoyun Zhang,
Hairu Huang,
Zhuoyue Shi,
Yue Feng,
Heran Li,
Hengdong Zhang,
Wenjun Ding,
Yan An
Affiliations
Rui Yan
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Jie Ding
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Yuanjie Wei
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Qianlei Yang
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Xiaoyun Zhang
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Hairu Huang
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Zhuoyue Shi
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Yue Feng
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Heran Li
Microwants International Ltd., Hong Kong, China
Hengdong Zhang
Department of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Jiangsu Preventive Medicine Association, Nanjing 210028, China
Wenjun Ding
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China
Yan An
Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Toxicology, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
Melatonin is an indoleamine hormone secreted by the pineal gland. It has antioxidation and anti-apoptosis effects and a clear protective effect against cardiovascular diseases. Our previous studies demonstrated that embryonic exposure to sodium arsenite (NaAsO2) can lead to an abnormal cardiac development. The aim of this study was to determine whether melatonin could protect against NaAsO2-induced generation of reactive oxygen species (ROS), oxidative stress, apoptosis, and abnormal cardiac development in a zebrafish (Danio rerio) model. We found that melatonin decreased NaAsO2-induced zebrafish embryonic heart malformations and abnormal heart rates at a melatonin concentration as low as 10−9 mol/L. The NaAsO2-induced oxidative stress was counteracted by melatonin supplementation. Melatonin blunted the NaAsO2-induced overproduction of ROS, the upregulation of oxidative stress-related genes (sod2, cat, gpx, nrf2, ho-1), and the production of antioxidant enzymes (Total SOD, SOD1, SOD2, CAT). Melatonin attenuated the NaAsO2-induced oxidative damage, DNA damage, and apoptosis, based on malonaldehyde and 8-OHdG levels and apoptosis-related gene expression (caspase-3, bax, bcl-2), respectively. Melatonin also maintained the control levels of heart development-related genes (nkx2.5, sox9b) affected by NaAsO2. In conclusion, melatonin protected against NaAsO2-induced heart malformations by inhibiting the oxidative stress and apoptosis in zebrafish.
