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Insights into enhanced toxic effects by the binary mixture of carbendazim and procymidone on hepatic lipid metabolism in mice

文献类型： 外文期刊

作者： Bao, Zhiwei 1 ; Wang, Dou 2 ; Zhao, Yao 1 ; Luo, Ting 2 ; Yang, Guilin 2 ; Jin, Yuanxiang 1 ;

作者机构： 1.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310032, Peoples R China

2.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, State Key Lab Managing Biot & Chem Threats Qual &, Lab Hangzhou Risk Assessment Agr Prod,Minist Agr, Hangzhou 310021, Zhejiang, Peoples R China

3.Xianghu Lab, Hangzhou 311231, Peoples R China

关键词： Fungicides; Joint toxicity; Lipid metabolism; Metabolomics; Mice

期刊名称：SCIENCE OF THE TOTAL ENVIRONMENT （ 影响因子：9.8； 五年影响因子：9.6 ）

ISSN： 0048-9697

年卷期： 2023 年 882 卷

页码：

收录情况： SCI

摘要： Carbendazim (CBZ) and procymidone (PRO) are two widely used fungicides in agriculture. However, there are still gaps in knowledge regarding about the potential hazards of joint exposure to CBZ and PRO in animals. Here, 6-week-old ICR mice were exposed to CBZ, PRO and CBZ + PRO for 30 days, and metabolomics were performed to discover the mechanism by which the mixture enhanced the effects on lipid metabolism. Co-exposure to CBZ + PRO elevated the body weights, relative liver weights and relative epididymis fat weights, but not in the single exposure groups. Molecular docking analysis suggested that CBZ and PRO combined with peroxisome proliferator-activated re-ceptor (PPAR gamma) at the same amino acid site as the agonist rosiglitazone. The RT-qPCR and WB results demonstrated that the levels of PPAR gamma were higher in the co-exposure group than in the single exposure groups. In addition, hundreds of differential metabolites were discovered by metabolomics and enriched in different pathways, such as pentose phos-phate pathway and purine metabolism. A unique effect, a decrease in glucose-6-phosphate (G6P) that promoted more NADPH production, was observed in the CBZ + PRO group. These results demonstrated that exposure to CBZ + PRO caused more serious lipid metabolism disorder in the liver than exposure to a single fungicide, which could provide some new insight for the toxic effects after fungicides joint exposure.

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