Volume 36, Number 5-6, September-December 2005
|Page(s)||799 - 810|
|How to cite this article||Vet. Res. (2005) 799-810|
Bioactivation of zearalenone by porcine hepatic biotransformationHassan Malekinejad, Roel Franciscus Maas-Bakker and Johanna Fink-Gremmels
Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16, 3508 TD Utrecht, The Netherlands
(Received 18 June 2004; accepted 4 April 2005)
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 -oestradiol as a positive control. The results obtained demonstrate that the oestrogenic potency of ZEA derivatives could be ranked in the following order: - zearalenol > -zearalanol > zearalenone > -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 -zearalenol is the main hepatic metabolite of zearalenone in pigs, and it is assumed that 3- and 3-hydroxysteroid dehydrogeneases are involved in the hepatic biotransformation, since the formation of -zearalenol and -zearalenol could be inhibited by prototypic substrates for either enzyme. The bioactivation of ZEA into the more active -zearalenol seems to provide a possible explanation for the observed high sensitivity of pigs towards feedingstuffs contaminated with the mycotoxin.
Key words: zearalenone / MCF-7 cells / oestrogenic effects / biotransformation / pigs
Corresponding author: Johanna Fink-Gremmels J.Fink@vfft.vet.uu.nl
© INRA, EDP Sciences 2005
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