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 17β-oestradiol as a positive control. The results obtained demonstrate that the oestrogenic potency of ZEA derivatives could be ranked in the following order: α- zearalenol > α-zearalanol > zearalenone > β-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 α-zearalenol is the main hepatic metabolite of zearalenone in pigs, and it is assumed that 3α- and 3β-hydroxysteroid dehydrogeneases are involved in the hepatic biotransformation, since the formation of α-zearalenol and β-zearalenol could be inhibited by prototypic substrates for either enzyme. The bioactivation of ZEA into the more active α-zearalenol seems to provide a possible explanation for the observed high sensitivity of pigs towards feedingstuffs contaminated with the mycotoxin. © INRA, EDP Sciences, 2005.