The role of miRNA-26a-5p and target gene socs1a in flutolanil induced hepatotoxicity of zebrafish at environmental relevant levels

文献类型： 外文期刊

第一作者： Yang, Yang

作者： Yang, Yang;Xu, Xiyan;Chang, Jinhe;Li, Yuanbo;Xu, Xiyan;Zheng, Yongquan;He, Bin;Li, Yuanbo

作者机构：

关键词： Flutolanil; Environmental concentration; Zebrafish; HepG2; Hepatotoxicity; miRNAs-mRNAs

期刊名称：ENVIRONMENTAL POLLUTION （ 影响因子：8.9； 五年影响因子：9.5 ）

ISSN： 0269-7491

年卷期： 2023 年 335 卷

页码：

收录情况： SCI

摘要： Flutolanil has been detected worldwide in aquatic environment and fish, which has become an undeniable stressor on ecosystem and human health. Flutolanil has been reported to be toxic to aquatic organisms. However, the pathophysiological and molecular mechanism behind the detrimental effects remains obscure. Here we reported hepatotoxicity induced by flutolanil in HepG2 cells and zebrafish, as revealed by toxicokinetic, HE staining, miRNAs-mRNAs sequencing, molecular dynamic simulations and dual luciferase reporter assays. Collectively, our results indicated that flutolanil could be absorbed by and accumulated in the liver of zebrafish, causing hepatic vacuolar degeneration, steatosis and nuclear condensation and abnormal liver function, where its exposure at environmental levels disrupted the expressions of miRNA-26a-5p and its target gene socs1a by mediating JAK-STAT signaling pathway, which was partially responsible for hepatotoxicity, correlated with oxidative stress, cell apoptosis, inflammation, cell cycle disorder and mitochondrial dysfunction. These findings suggest that miRNA-26a-5p/socs1a can serve as potential biomarkers of hepatotoxicity in zebrafish following exposure to flutolanil. This uncovered route will provide a new tool for the risk assessment of flutolanil and a guide to proper use of flutolanil and environmental remedy, and open up a new horizon for liver disease assessment.

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