Metabolism of nivalenol and nivalenol-3-glucoside in rats.

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 (NIV3 G) in rats. To that end, 350 µg/kg body weight of NIV and the equimolar dose of NIV3 G 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 NIV3 G metabolites in rat urine and feces, seven novel NIV- and NIV3 G metabolites including NIV sulfonates (NIVS) 1, 2 and 3, deepoxy-NIV (DNIV), DNIV sulfonate 2, NIV3 G sulfonate (NIV3 GS) 2 and NIV-3-glucuronide were produced, isolated and characterized. Subsequently, LC-MS/MS based methods for determination of NIV, NIV3 G 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 NIV3 G. The majority of NIV and NIV3 G metabolites was excreted into feces, with DNIV and NIVS 2 as major NIV metabolites and NIV3 GS 2 and DNIV as major metabolites of NIV3 G. Only 1.5% of the administered NIV3 G was recovered in urine, with NIV3 G itself as major urinary metabolite. The biological recovery of free NIV in urine was approximately 30 times lower after treatment with NIV3 G than after administration of NIV, indicating that exposure of rats to NIV3 G results in lower toxicity than exposure to NIV.