title: Metabolism of Zearalenone and Its Major Modified Forms in Pigs.
abstract: TheFusariummycotoxin 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.
authors.affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria. sabina.binder@boku.ac.at.
authors.forename: Sabina B
authors.initials: SB
authors.lastname: Binder
authors.affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria. heidi.schwartz@boku.ac.at.
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Schwartz-Zimmermann
authors.affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria. elisabeth.varga@boku.ac.at.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Varga
authors.affiliation: BIOMIN Research Center, Technopark 1, 3430 Tulln, Austria. gerlinde.bichl@biomin.net.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Bichl
authors.affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 24, 3430 Tulln, Austria. herbert.michlmayr@boku.ac.at.
authors.forename: Herbert
authors.initials: H
authors.lastname: Michlmayr
authors.affiliation: Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 24, 3430 Tulln, Austria. gerhard.adam@boku.ac.at.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Adam
authors.affiliation: Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, 3430 Tulln, Austria. franz.berthiller@boku.ac.at.
authors.forename: Franz
authors.initials: F
authors.lastname: Berthiller
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005516:Food Microbiology; D005960:Glucosides / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D006868:Hydrolysis; D007408:Intestinal Absorption; D066237:Intestinal Elimination; D008297:Male; D050217:Metabolic Detoxication, Phase II; D065667:Renal Elimination; D034421:Sus scrofa; D053719:Tandem Mass Spectrometry; D015025:Zearalenone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity / Q000652:urine; D015029:Zeranol / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D005960:Glucosides; D020719:Glucuronides; C029659:zearalenol; C000597750:zearalenone-14-glucuronide; C068796:zearalenone-4-sulfate; D015025:Zearalenone; D015029:Zeranol
keywords: bioavailability; cleavage; enzymatic hydrolysis; gastrointestinal tract; high performance liquid chromatography tandem mass spectrometry; masked mycotoxins; mycotoxins; plant metabolites