数字农科院2.0

First insight into the formation of transformation products of a biopesticide guvermectin in rat and its health risk

文献类型： 外文期刊

作者： Yuan Shi;Xinglu Pan;Xiaohu Wu;Jun Xu;Wensheng Xiang;Zhiyuan Li;Yongquan Zheng;Xiangjing Wang;Fengshou Dong

作者机构：

关键词： Biotransformation;CYP450s;Guvermectin;Oral toxicity;UPLC-QTOF/MS

期刊名称： Science of the Total Environment

ISSN： 0048-9697

年卷期： 2024 年 954 卷

页码：

收录情况： SCIE（2024版） ; ; EI（2024版）

摘要： Guvermectin is a new chemical isolated from the microbial metabolites and is registered as a novel plant growth regulator. However, the biotransformation behavior and toxicity of guvermectin to mammals remain unclear and have unknown implications for consumers or occupationally exposed persons. Therefore, we investigated the biotransformation of guvermectin in vivo and in vitro, its effects on CYP450s activities, and its oral toxicity in rats. The results showed that guvermectin could be rapidly absorbed when administered orally and eliminated rapidly in the serum, with a half-life of 6.3 h. Four phase І metabolism products of guvermectin in the serum were screened and identified using UPLC-QTOF/MS. Two products, adenine and psicofuramine, were confirmed using reference standards. Hydrolysis and oxidation reactions were the main transformation pathways. Oral toxicity tests in rats showed that guvermectin exhibited light toxicity to rats (LC50 > 5000 mg/kg b.w.). However, an in vitro probe drug experiment revealed that guvermectin could induce CYP2D6 activity, and a lower concentration of guvermectin exhibited a stronger effect on CYP2D6 than higher concentration (1.38-fold). Molecular docking studies implied that guvermectin was an antagonist of CYP1A2, CYP2C9, and CYP3A4. These findings provided a better understanding of the environmental and human health risks associated with guvermectin and promote its rational use. However, the potential risk of endocrine disruption can not be ignored due to the presence of nucleoside-like metabolites.

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