Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.
Ecotoxicol Environ Saf. 2022 Nov;246:114184. doi: 10.1016/j.ecoenv.2022.114184. Epub 2022 Oct 13.
Bioaccumulation and biotransformation are critical factors that affect the release of easily metabolizable chemicals to cause human toxicity. The glucoside-type modified mycotoxin Zearalenone-14-Glucoside (Z14G) has attracted global attention for its high occurrence in foodstuffs and the potential threat to humans as its high rate of transformation into parent forms. Given the limited toxicokinetics information, this study assessed the absorption, distribution, biotransformation and excretion of Z14G, aiming to define the potential risk of Z14G. The toxicokinetics of Z14G were assessed after intravenous (IV) or oral administration (PO) in SD rats at doses of 10 mg/kg·b.w. In addition, comparative work with the parent mycotoxin ZEN was performed in parallel. The determination of Z14G and its metabolites (ZEN, α-zearalenol, β-zearalenol, α-zearalanol, β-zearalanol) proceeded with a sensitive UHPLC-MS/MS method. Our research indicated that Z14G readily disappeared from the blood, and distributed throughout the tissues via transformation into its parent form ZEN, and excreted primarily through urine. More importantly, the metabolite α-ZEL was observed in most analyzed tissue, urine and feces samples. Overall, our findings highlight the importance of biotransformation with regard to Z14G, providing critical insight for the health risk assessment of co-exposure of humans to glucoside-type modified mycotoxins.
生物累积和生物转化是影响易代谢化学物质释放并导致人类毒性的关键因素。葡糖苷型修饰真菌毒素 Zearalenone-14-Glucoside(Z14G)在食品中高频率出现,并且由于其向母体形式转化的高转化率,对人类构成潜在威胁,因此引起了全球关注。鉴于有限的毒代动力学信息,本研究评估了 Z14G 的吸收、分布、生物转化和排泄,旨在确定 Z14G 的潜在风险。在 SD 大鼠中以 10mg/kg·bw 的剂量静脉内(IV)或口服(PO)给予 Z14G 后,评估了其毒代动力学。此外,还与母体真菌毒素 ZEN 进行了平行比较工作。采用灵敏的 UHPLC-MS/MS 方法测定 Z14G 及其代谢物(ZEN、α-玉米赤霉烯醇、β-玉米赤霉烯醇、α-玉米赤霉烯醇、β-玉米赤霉烯醇)。我们的研究表明,Z14G 很快从血液中消失,并通过转化为母体形式 ZEN 分布到组织中,主要通过尿液排泄。更重要的是,在大多数分析的组织、尿液和粪便样本中都观察到代谢物 α-ZEL。总体而言,我们的研究结果强调了 Z14G 生物转化的重要性,为评估人类同时接触葡糖苷型修饰真菌毒素的健康风险提供了关键的见解。