Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Str. 20, Tulln 3430, Austria.
Christian Doppler Laboratory for Mycotoxin Metabolism, Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Str. 20, Tulln 3430, Austria.
Toxicol Lett. 2019 May 15;306:43-52. doi: 10.1016/j.toxlet.2019.02.006. Epub 2019 Feb 12.
Plant-derived mycotoxin conjugates like deoxynivalenol-3-glucoside can be partly hydrolyzed to their aglycones in vivo, albeit to different extent depending on the mycotoxin conjugate and on the animal species. The aim of this work was to investigate the metabolization of the trichothecene mycotoxin nivalenol (NIV) and the fate of its modified form NIV-3-glucoside (NIV3G) in rats. To that end, 350 μg/kg body weight of NIV and the equimolar dose of NIV3G were administered to six rats by gavage in a 5 × 6 design and excreta were collected for 2 days after each treatment. For further analysis of NIV and NIV3G metabolites in rat urine and feces, seven novel NIV- and NIV3G metabolites including NIV sulfonates (NIVS) 1, 2 and 3, deepoxy-NIV (DNIV), DNIV sulfonate 2, NIV3G sulfonate (NIV3GS) 2 and NIV-3-glucuronide were produced, isolated and characterized. Subsequently, LC-MS/MS based methods for determination of NIV, NIV3G and their metabolites in excreta samples were developed, validated and applied. The biological recoveries of administered toxins in the form of their fecal and urinary metabolites were 57 ± 21% for NIV and 94 ± 36% for NIV3G. The majority of NIV and NIV3G metabolites was excreted into feces, with DNIV and NIVS 2 as major NIV metabolites and NIV3GS 2 and DNIV as major metabolites of NIV3G. Only 1.5% of the administered NIV3G was recovered in urine, with NIV3G itself as major urinary metabolite. The biological recovery of free NIV in urine was approximately 30 times lower after treatment with NIV3G than after administration of NIV, indicating that exposure of rats to NIV3G results in lower toxicity than exposure to NIV.
植物来源的霉菌毒素缀合物，如脱氧雪腐镰刀菌烯醇-3-葡萄糖苷，可在体内部分水解为其配基，但不同的霉菌毒素缀合物和动物物种对其水解程度不同。本研究的目的是研究玉米赤霉烯酮毒素 nivalenol（NIV）及其修饰形式 NIV-3-葡萄糖苷（NIV3G）在大鼠体内的代谢情况和其命运。为此，通过灌胃方式向 6 只大鼠给予 350μg/kg 体重的 NIV 和等摩尔剂量的 NIV3G，在每种处理后收集 2 天的排泄物。为了进一步分析大鼠尿液和粪便中 NIV 和 NIV3G 的代谢物，共分离鉴定出 7 种新型 NIV 和 NIV3G 代谢物，包括 NIV 硫酸盐（NIVS）1、2 和 3、去氧玉米赤霉烯酮（DNIV）、DNIV 硫酸盐 2、NIV3G 硫酸盐（NIV3GS）2 和 NIV-3-葡萄糖醛酸苷。随后，建立并验证了基于 LC-MS/MS 的方法，用于测定排泄物样品中 NIV、NIV3G 及其代谢物的含量。以粪便和尿液代谢物形式给予的毒素的生物回收率分别为 NIV 57±21%和 NIV3G 94±36%。NIV 和 NIV3G 的大部分代谢物随粪便排出，DNIV 和 NIVS 2 为主要 NIV 代谢物，NIV3GS 2 和 DNIV 为 NIV3G 的主要代谢物。给予的 NIV3G 中仅有 1.5%在尿液中回收，其中 NIV3G 本身为主要的尿液代谢物。与给予 NIV 相比，大鼠给予 NIV3G 后尿液中游离 NIV 的生物回收率约低 30 倍，表明大鼠暴露于 NIV3G 导致的毒性低于暴露于 NIV。
