title: Bioactivation of zearalenone by porcine hepatic biotransformation.
abstract: Zearalenone (ZEA) is a resorcylic acid lactone derivative produced by various Fusarium species that are widely found in food and feeds. The structure of zearalenone is flexible enough to allow a conformation able to bind to mammalian oestrogen receptors, where it acts as an agonist. Using oestrogen-dependent Human Breast Cancer (MCF-7) cells, the oestrogenic activity of zearalenone and its derivatives were compared using 17 beta-oestradiol as a positive control. The results obtained demonstrate that the oestrogenic potency of ZEA derivatives could be ranked in the following order: alpha-zearalenol > alpha-zearalanol > zearalenone > beta-zearalenol. Since pigs have been reported to be among the most sensitive animal species, biotransformation studies with pig liver subcellular fractions were conducted. These studies indicated that alpha-zearalenol is the main hepatic metabolite of zearalenone in pigs, and it is assumed that 3 alpha- and 3 beta-hydroxysteroid dehydrogeneases are involved in the hepatic biotransformation, since the formation of alpha-zearalenol and beta-zearalenol could be inhibited by prototypic substrates for either enzyme. The bioactivation of ZEA into the more active alpha-zearalenol seems to provide a possible explanation for the observed high sensitivity of pigs towards feeding-stuffs contaminated with the mycotoxin.
authors.affiliation: Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16, 3508 TD Utrecht, The Netherlands.
authors.forename: Hassan
authors.initials: H
authors.lastname: Malekinejad
authors.forename: Roel Franciscus
authors.initials: RF
authors.lastname: Maas-Bakker
authors.forename: Johanna
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D000818:Animals; D001681:Biological Assay; D001711:Biotransformation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D015394:Molecular Structure; D013552:Swine; D013997:Time Factors; D015025:Zearalenone / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004968:Estrogens, Non-Steroidal; D004958:Estradiol; D015025:Zearalenone