School of Public Health Management, Jiangsu Health Vocational College, Nanjing 211800, PR China.
Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University, The Sixth People's Hospital of Nantong, Nantong 226011, PR China.
Ecotoxicol Environ Saf. 2024 Jul 1;279:116484. doi: 10.1016/j.ecoenv.2024.116484. Epub 2024 May 30.
Myclobutanil (MYC) is a common triazole fungicide widely applied in agriculture. MYC extensively exists in the natural environment and can be detected in organisms. However, little is known about MYC-induced embryonic developmental damage. This study aimed to unravel the cardiotoxicity of MYC and the underlying mechanisms, as well as the cardioprotective effect of curcumin (CUR, an antioxidant polyphenol) using the zebrafish model. Here, zebrafish embryos were exposed to MYC at concentrations of 0, 0.5, 1 and 2 mg/L from 4 to 96 h post fertilization (hpf) and cardiac development was assessed. As results, MYC reduced the survival and hatching rate, body length and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal cardiac morphology and function in myl7:egfp transgenic zebrafish, and downregulated cardiac developmental genes. MYC promoted oxidative stress through excessive reactive oxygen species (ROS) accumulation and suppressed the activities of antioxidant enzymes, triggering cardiomyocytic apoptosis via upregulated expression of apoptosis-related genes. These adverse toxicities could be significantly ameliorated by the antioxidant properties of CUR, indicating that CUR rescued MYC-induced cardiotoxicity by inhibiting oxidative stress and apoptosis. Overall, our study revealed the potential mechanisms of oxidative stress and apoptosis in MYC-induced cardiotoxicity in zebrafish and identified the cardioprotection of CUR in this pathological process.
环戊菌唑（MYC）是一种常见的三唑类杀菌剂，广泛应用于农业。MYC 广泛存在于自然环境中，并能在生物体内检测到。然而，关于 MYC 诱导的胚胎发育损伤知之甚少。本研究旨在利用斑马鱼模型揭示 MYC 的心脏毒性及其潜在机制，以及姜黄素（CUR，一种抗氧化多酚）的心脏保护作用。在此，斑马鱼胚胎从受精后 4 至 96 小时（hpf）分别暴露于 0、0.5、1 和 2mg/L 的 MYC 中，并评估心脏发育情况。结果表明，MYC 降低了存活率和孵化率、体长和心率，但增加了畸形率和自发运动。MYC 在 myl7:egfp 转基因斑马鱼中引起心脏形态和功能异常，并下调了心脏发育基因。MYC 通过过度积累活性氧（ROS）引起氧化应激，并抑制抗氧化酶的活性，通过上调凋亡相关基因的表达引发心肌细胞凋亡。抗氧化特性的 CUR 可显著改善这些不良毒性，表明 CUR 通过抑制氧化应激和凋亡，挽救了 MYC 诱导的心脏毒性。总的来说，本研究揭示了 MYC 诱导的斑马鱼心脏毒性中氧化应激和凋亡的潜在机制，并确定了 CUR 在这一病理过程中的心脏保护作用。
