Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine , Ghent University , Salisburylaan 133 , 9820 Merelbeke , Belgium.
Sciensano , Juliette Wytsmanstraat 14 , 1050 Elsene , Belgium.
J Agric Food Chem. 2019 Mar 27;67(12):3448-3458. doi: 10.1021/acs.jafc.8b05838. Epub 2019 Mar 13.
The aim of this study was to determine the toxicokinetic characteristics of ZEN and its modified forms, α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), zearalenone-14-glucoside (ZEN14G), and zearalenone-14-sulfate (ZEN14S), including presystemic and systemic hydrolysis in pigs. Crossover pig trials were performed by means of intravenous and oral administration of ZEN and its modified forms. Systemic plasma concentrations of the administered toxins and their metabolites were quantified and further processed via tailor-made compartmental toxicokinetic models. Furthermore, portal plasma was analyzed to unravel the site of hydrolysis, and urine samples were analyzed to determine urinary excretion. Results demonstrate complete presystemic hydrolysis of ZEN14G and ZEN14S to ZEN and high oral bioavailability for all administered compounds, with further extensive first-pass glucuronidation. Conclusively, the modified-ZEN forms α-ZEL, β-ZEL, ZEN14G, and ZEN14S contribute to overall ZEN systemic toxicity in pigs and should be taken into account for risk assessment.
本研究旨在确定玉米赤霉烯酮（ZEN）及其修饰形式α-玉米赤霉烯醇（α-ZEL）、β-玉米赤霉烯醇（β-ZEL）、玉米赤霉烯酮-14-葡萄糖苷（ZEN14G）和玉米赤霉烯酮-14-硫酸盐（ZEN14S）的毒代动力学特征，包括猪体内的前体系统和全身水解。通过静脉和口服给予 ZEN 及其修饰形式进行了交叉猪试验。对给予的毒素及其代谢物的系统血浆浓度进行了定量，并通过定制的房室毒代动力学模型进行了进一步处理。此外，还分析了门脉血浆以揭示水解部位，并分析了尿液样本以确定尿排泄。结果表明，ZEN14G 和 ZEN14S 完全在前体系统中水解为 ZEN，所有给予的化合物的口服生物利用度都很高，进一步广泛地发生了首过葡萄糖醛酸化。总之，修饰后的 ZEN 形式α-ZEL、β-ZEL、ZEN14G 和 ZEN14S 有助于猪体内 ZEN 的整体系统毒性，应在风险评估中考虑到这些因素。
