Neonatology, Anxi County Hospital, Quanzhou, People's Republic of China.
Scientific Research Center, Anxi County Hospital, Quanzhou, People's Republic of China.
Birth Defects Res. 2024 May;116(5):e2350. doi: 10.1002/bdr2.2350.
Cyprodinil is a widely used fungicide with broad-spectrum activity, but it has been associated with cardiac abnormalities. (-)-Epicatechin gallate (ECG), a natural polyphenolic compound, has been shown to possess protective properties in cardiac development.
In this study, we investigated whether ECG could mitigate cyprodinil-induced heart defects using zebrafish embryos as a model. Zebrafish embryos were exposed to cyprodinil with or without ECG.
Our results demonstrated that ECG significantly improved the survival rate, embryo movement, and hatching delay induced by cyprodinil. Furthermore, ECG effectively ameliorated cyprodinil-induced cardiac developmental toxicity, including pericardial anomaly and impairment of cardiac function. Mechanistically, ECG attenuated the cyprodinil-induced alterations in mRNA expression related to cardiac development, such as amhc, vmhc, tbx5, and gata4, as well as calcium ion channels, such as ncx1h, atp2a2a, and cdh2. Additionally, ECG was found to inhibit the activity of the aryl hydrocarbon receptor (AhR) signaling pathways induced by cyprodinil.
In conclusion, our findings provide evidence for the protective effects of ECG against cyprodinil-induced cardiac developmental toxicity, mediated through the inhibition of AhR activity. These findings contribute to a better understanding of the regulatory mechanisms and safe utilization of pesticide, such as cyprodinil.
环丙嘧啶是一种广泛使用的具有广谱活性的杀菌剂，但它与心脏异常有关。（-）-表儿茶素没食子酸酯（ECG）是一种天然多酚化合物，已被证明具有心脏发育的保护特性。
在这项研究中，我们使用斑马鱼胚胎作为模型，研究了 ECG 是否可以减轻环丙嘧啶引起的心脏缺陷。斑马鱼胚胎暴露于环丙嘧啶和/或 ECG 中。
我们的结果表明，ECG 显著提高了环丙嘧啶引起的存活率、胚胎运动和孵化延迟。此外，ECG 有效改善了环丙嘧啶引起的心脏发育毒性，包括心包异常和心脏功能损害。机制上，ECG 减轻了环丙嘧啶引起的与心脏发育相关的 mRNA 表达改变，如 amhc、vmhc、tbx5 和 gata4 以及钙通道，如 ncxlh、atp2a2a 和 cdh2。此外，还发现 ECG 抑制了环丙嘧啶诱导的芳烃受体（AhR）信号通路的活性。
总之，我们的发现为 ECG 对环丙嘧啶诱导的心脏发育毒性的保护作用提供了证据，这是通过抑制 AhR 活性介导的。这些发现有助于更好地理解农药（如环丙嘧啶）的调节机制和安全利用。
