title: Mouse tissue distribution and persistence of the food-born fusariotoxins Enniatin B and Beauvericin.
abstract: The fusariotoxins Enniatin B (Enn B) and Beauvericin (Bea) have recently aroused interest as food contaminants and as potential anticancer drugs. However, limited data are available about their toxic profile. Aim of this study was to investigate their pharmacological behavior in vivo and their persistence in mice. Therefore, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze the distribution of Enn B and Bea in selected tissue samples and biological fluids originating from mice treated intraperitoneally with these cyclohexadepsipeptides. Overall, no toxicological signs during life time or pathological changes were observed. Moreover, both fusariotoxins were found in all tissues and serum but not in urine. Highest amounts were measured in liver and fat demonstrating the moleculeś tendency to bioaccumulate in lipophilic tissues. While for Bea no metabolites could be detected, for Enn B three phase I metabolites (dioxygenated-Enn B, mono- and di-demethylated-Enn B) were found in liver and colon, with dioxygenated-Enn B being most prominent. Consequently, contribution of hepatic as well as intestinal metabolism seems to be involved in the overall metabolism of Enn B. Thus, despite their structural similarity, the metabolism of Enn B and Bea shows distinct discrepancies which might affect long-term effects and tolerability in humans.
authors.affiliation: Department of Public Health, Faculty of Pharmacy, University of Valencia, Av. Vicent A. Estellés s/n, 46100 Burjassot, Spain.
authors.forename: Yelko
authors.initials: Y
authors.lastname: Rodríguez-Carrasco
authors.affiliation: Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria; Comprehensive Cancer Center of the Medical University, Spitalgasse 23, 1090 Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Heilos
authors.affiliation: Technische Universität Berlin, Institut für Chemie, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Lennart
authors.initials: L
authors.lastname: Richter
authors.affiliation: Technische Universität Berlin, Institut für Chemie, Straße des 17. Juni 124, 10623 Berlin, Germany.
authors.forename: Roderich D
authors.initials: RD
authors.lastname: Süssmuth
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria; Comprehensive Cancer Center of the Medical University, Spitalgasse 23, 1090 Vienna, Austria; Research Platform "Translational Cancer Therapy Research", Vienna, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Heffeter
authors.affiliation: Department of Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz Str. 20, 3430 Tulln, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sulyok
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Währingergürtel 18-20, Vienna, Austria; Ludwig Boltzmann Institute for Cancer Research, Währingerstraße 13a, Vienna, Austria,; Institute of Laboratory Animal Pathology, Veterinary University of Vienna, Veterinärplatz 1, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria; Comprehensive Cancer Center of the Medical University, Spitalgasse 23, 1090 Vienna, Austria; Research Platform "Translational Cancer Therapy Research", Vienna, Austria. Electronic address: walter.berger@meduniwien.ac.at.
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.affiliation: Department of Pharmacology and Toxicology, University of Vienna, Althanstr. 14, A-1090 Vienna, Austria; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria; Comprehensive Cancer Center of the Medical University, Spitalgasse 23, 1090 Vienna, Austria. Electronic address: rita.dornetshuber@univie.ac.at.
authors.forename: Rita
authors.initials: R
authors.lastname: Dornetshuber-Fleiss
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000493:pharmacokinetics; D001682:Biological Availability; D002853:Chromatography, Liquid; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D047630:Depsipeptides / Q000378:metabolism / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D013605:T-2 Toxin / Q000378:metabolism / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; C100264:enniatins; C004456:beauvericin; D013605:T-2 Toxin
keywords: Beauvericin; Enniatin B; In vivo; LC-MS/MS; Metabolism