(-)-表儿茶素没食子酸酯通过抑制斑马鱼体内的芳基烃受体改善环丁胺诱导的心脏发育缺陷

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2024-05-18 DOI:10.1002/bdr2.2350

Dongqin Huang, Yuchao Su, Mingmei Li, Chengwei Xie, Weibin Hu, Shuxiang Wang, Nanmei Zheng, Jianhui Chen, Yueyun Lin, Weize Cai, Jianjia Xiao, Baojia Chen, Nanping Hu, Fushan Zhou

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引用次数: 0

摘要

背景：嘧菌酯是一种广泛使用的杀真菌剂，具有广谱活性，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，已被证明对心脏发育具有保护作用：在这项研究中，我们以斑马鱼胚胎为模型，研究了表儿茶素是否能减轻环丙地尼所诱发的心脏缺陷。将斑马鱼胚胎暴露于含或不含心电图的环丙地尼中：结果：我们的研究结果表明，心电图能明显改善环丙地尼诱导的斑马鱼胚胎存活率、胚胎运动和孵化延迟。此外，心电图还能有效改善环丙地尼诱导的心脏发育毒性，包括心包畸形和心脏功能损害。从机理上讲，ECG可减轻环丙地尼诱导的与心脏发育有关的mRNA表达变化，如amhc、vmhc、tbx5和gata4，以及钙离子通道，如ncx1h、atp2a2a和cdh2。此外，还发现心电图抑制了环丙地尼诱导的芳基烃受体（AhR）信号通路的活性：总之，我们的研究结果为心电图通过抑制 AhR 活性对环丙地尼诱导的心脏发育毒性的保护作用提供了证据。这些研究结果有助于更好地理解农药（如环丙地尼）的调控机制和安全使用。

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(−)-Epicatechin gallate ameliorates cyprodinil-induced cardiac developmental defects through inhibiting aryl hydrocarbon receptor in zebrafish

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.