Bioactivation of zearalenone by porcine hepatic biotransformation
Résumé
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 feedingstuffs contaminated with the mycotoxin.
Origine : Accord explicite pour ce dépôt
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