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Fungicide bromuconazole has the potential to induce hepatotoxicity at the physiological, metabolomic and transcriptomic levels in rats

文献类型： 外文期刊

作者： Wu, Shuchun 1 ; Ji, Xiaofeng 3 ; Wang, Jianmei 3 ; Wu, Huizhen 3 ; Han, Jianzhong 2 ; Zhang, Hu 3 ; Xu, Jie 3 ; Qian, Min 1 ;

作者机构： 1.Hangzhou Med Coll, Hangzhou, Peoples R China

2.Zhejiang Gongshang Univ, Coll Food Sci & Biotechnol, Hangzhou, Peoples R China

3.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, Zhejiang Prov Key Lab Food Safety, Hangzhou, Peoples R China

关键词： Bromuconazole; Hepatotoxicity; Physiological; Metabolomics; Transcriptomic; Rats

期刊名称：ENVIRONMENTAL POLLUTION （ 影响因子：8.071； 五年影响因子：8.35 ）

ISSN： 0269-7491

年卷期： 2021 年 280 卷

页码：

收录情况： SCI

摘要： Bromuconazole (BROMU), a representative triazole fungicide, has been widely used in agriculture for its low cost and highly efficiency against various fungi. BROMU residue was often detected in the environment and food chain, even though there is indication of health risk to animals, and in humans. However, the data related to the toxicity of BROMU in animals remains unclear, and the mechanism is still not fully elucidated. Here, male adult rats were exposed to 0, 13.8, 32.8 and 65.6 mg/kg/d of BROMU for 10 days by oral gavage. It was observed that short time BROMU exposure not only caused liver histological damage, including vacuolar degeneration of hepatocytes with pyknotic nuclei, but also changed the levels of some hepatic physiological parameters, including aspartate transaminase (AST), triglyceride (TG), pyruvate and total cholesterol (TC), indicating that BROMU causes hepatotoxicity in rats. In addition, according to the transcriptomics and metabolomics analysis, a total of 58 metabolites and 259 genes significantly changed in the high-dose BROMU treated group. Although several different pathways are involved, lipid metabolism- and bile acids metabolism-related pathways were highlighted in both metabolomics and transcriptomics analysis. More importantly, further validation had proven that BROMU could not only interact with peroxisome proliferator-activated receptor gamma (PPAR-gamma), but also significantly decrease its protein and gene expression in the liver, supporting that BROMU decreased the TG synthesis via inhibiting the PPAR-y pathway. These results clearly showed that BROMU exposure could result in hepatotoxicity at metabolomic and transcriptomic level in rats. These observations could provide some important steps toward understanding the mechanism underlying BROMU-induced mammalian toxicity. (C) 2021 Elsevier Ltd. All rights reserved.

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