Abstract
The Fusarium mycotoxin zearalenone (ZEN) can be conjugated with polar molecules, like sugars or sulfates, by plants and fungi. To date, the fate of these modified forms of ZEN has not yet been elucidated in animals. In order to investigate whether ZEN conjugates contribute to the total ZEN exposure of an individual, ZEN (10 µg/kg b.w.) and equimolar amounts of two of its plant metabolites (ZEN-14-O-β-glucoside, ZEN-16-O-β-glucoside) and of one fungal metabolite (ZEN-14-sulfate) were orally administered to four pigs as a single bolus using a repeated measures design. The concentrations of ZEN, its modified forms and its mammalian metabolites ZEN-14-glucuronide, α-zearalenol (α-ZEL) and α-ZEL-14-glucuronide in excreta were analyzed by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) based methods. The biological recovery of ZEN in urine was 26% ± 10%, the total biological recovery in excreta was 40% ± 8%. Intact ZEN-14-sulfate, ZEN-14-O-β-glucoside and ZEN-16-O-β-glucoside were neither detected in urine nor in feces. After ZEN-14-sulfate application, 19% ± 5% of the administered dose was recovered in urine. In feces, no ZEN metabolites were detected. The total biological recoveries of ZEN-14-O-β-glucoside and ZEN-16-O-β-glucoside in the form of their metabolites in urine were 19% ± 11% and 13% ± 7%, respectively. The total biological recoveries in urine and feces amounted to 48% ± 7% and 34 ± 3%. An explanation for the low biological recoveries could be extensive metabolization by intestinal bacteria to yet unknown metabolites. In summary, ZEN-14-sulfate, ZEN-14-O-β-glucoside, and ZEN-16-O-β-glucoside were completely hydrolyzed in the gastrointestinal tract of swine, thus contributing to the overall toxicity of ZEN.
Highlights
Mycotoxins are natural secondary metabolites produced by various species of fungi and are able to exert toxic effects in humans, animals, and plants [1]
The results of this study extend the current knowledge about the in vivo metabolization of some ZEN conjugates, contributing significantly to the further risk assessment of these compounds
The plant and fungal ZEN metabolites ZEN-14-Glc, ZEN-16-Glc, and ZEN-14-S were readily hydrolyzed to ZEN and converted to other still-unknown metabolites in the GI tract of pigs
Summary
Mycotoxins are natural secondary metabolites produced by various species of fungi and are able to exert toxic effects in humans, animals, and plants [1]. Zearalenone (ZEN), one of the most important mycotoxins, can cause fertility and reproduction disorders in mammals. Gilts are the most sensitive species to ZEN exposure [2]. ZEN possesses an estrogenic effect, which manifests itself. Toxins 2017, 9, 56; doi:10.3390/toxins9020056 www.mdpi.com/journal/toxins clinically in hyperestrogenism. Prepubertal females react sensitively [3].
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