Toxicokinetics of alpha-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans

文献类型： 外文期刊

第一作者： Yang, Shupeng

作者： Yang, Shupeng;Zhou, Jinhui;Li, Yi;Zhang, Huiyan;Sun, Feifei;Li, Yanshen;De Boevre, Marthe;De Saeger, Sarah;Zhang, Huiyan;Sun, Feifei

作者机构：

关键词： Alpha-zearalenol-14 glucoside; Masked mycotoxins; Metabolism; Zearalenone

期刊名称：JOURNAL OF HAZARDOUS MATERIALS （ 影响因子：10.588； 五年影响因子：10.129 ）

ISSN： 0304-3894

年卷期： 2020 年 393 卷

页码：

收录情况： SCI

摘要： Alpha-zearalenol (alpha-ZEL) and its masked form alpha-zearalenol-14 glucoside (alpha-ZEL-14G) have much higher oestrogenic activity than zearalenone. Owing to very limited toxicokinetic and metabolic data, no reference points could be established for risk assessment. To circumvent it, the toxicokinetic, metabolic profiles, and phenotyping of alpha-ZEL and alpha-ZEL-14G were comprehensively investigated in this study. As a result, the plasma concentrations of alpha-ZEL and alpha-ZEL-14G were all below LOQ after oral administration, while after iv injection, both could be significantly bio-transformed into various metabolites. A complete hydrolysis of alpha-ZEL-14G contributed to alpha-ZEL overall toxicity. Additionally, 31 phase I and 10 phase II metabolites of alpha-ZEL, and 9 phase I and 5 phase II metabolites were identified for alpha-ZEL-14G. For alpha-ZEL, hydroxylation, dehydrogenation, and glucuronidation were the major metabolic pathways, while for alpha-ZEL-14G, it was deglycosylation, reduction, hydroxylation, and glucuronidation. Significant metabolic differences were observed for alpha-ZEL and alpha-ZEL-14G in the liver microsomes of rats, chickens, swine, goats, cows and humans. Phenotyping studies indicated that alpha-ZEL and alpha-ZEL-14G were mediated by CYP 3A4, 2C8, and 1A2. Moreover, the deglycosylation of alpha-ZEL-14G was critically mediated by CES-I and CES-II. The acquired data would provide fundamental perspectives for risk evaluation of mycotoxins and their modified forms.

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