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Thifluzamide Induces The Toxic Effects On Zebrafish (Danio Rerio) Via Inhibition Of Succinate Dehydrogenase (Sdh)

文献类型： 外文期刊

作者： Yang, Y; Dong, FS; Liu, XG; Xu, J; Wu, XH; Zheng, YQ

作者机构：

关键词： Thifluzamide; Zebrafish; Toxicity; Chitinase; Sdh

期刊名称： ENVIRONMENTAL POLLUTION

ISSN： 0269-7491

年卷期： 2020 年 265 卷

页码：

收录情况： JCR（2021版） ; EI（2021版）

摘要： Thifluzamide is widely used in treatment of rice diseases and has potential toxicity on aquatic organism. Although previous studies have focused on the toxic effect of thifluzamide in zebrafish, no consistent conclusions have been reached. To help to elucidate the toxic mechanism, qualities of liver and mitochondria were evaluated. The global changes in the transcriptome of zebrafish after exposure to thifluzamide were measured. Based on this, the expression and activities of chitinase and succinate dehydrogenase (SDH) were further assayed. And the targeted site of thifluzamide in zebrafish was confirmed by dock study and co-exposure study. Here we report that developmental inhibition was observed along with presence of liver and mitochondrial damage. The expression of SDHa-d and genes related to mitochondrial DNA (mtDNA) replicate and mitochondrial complexes were significantly altered. And, as the top differentially expressed genes, the expression of chia.1-6 did show apparent changes, but differences of chitinase activity between exposure groups and the controls did not reach significance. In line with that, dock study showed that the binding potentials of thifluzamide toward zebrafish chitinase and SDH exhibited in the following order: SDH> chitinase. And sdhb-sdhc-sdhd (Qp site) showed the highest binding activity toward thifluzamide. The joint exposure (thifluzamide + Q10) significantly improved the survival of zebrafish compared with single thifluzamide exposure. These results indicate that SDH, especially Qp-site, may be the target of thifluzamide in zebrafish and inhibition of SDH activity may be at least in partial responsible for the toxicity of thifluzamide in zebrafish. In addition, the antagonistic effect of Q10 on thifluzamide toxicity in zebrafish suggests that Q10 may be a useful adjunct to detoxification. (C) 2020 Elsevier Ltd. All rights reserved.

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