The metabolism of zearalenone in subcellular fractions from rabbit and hen hepatocytes and its estrogenic activity in rabbits.

The in vitro reduction of zearalenone (ZEN) by subcellular fractions from hen and rabbit hepatocytes clearly shows species-specific differences in the cofactor requirements, rate of metabolism and production of metabolites. The presence of NADH as cofactor in the reaction mixtures enhanced only the reducing activity of the microsomal fraction from rabbit hepatocytes, while NADPH enhanced the reducing activities of the cytosolic fraction from rabbit and both the microsomal and cytosolic fractions from hen hepatocytes. Furthermore, we observed that hen hepatocytes metabolize faster and produce beta-zearalenol (ZEL) as the major metabolite, whereas rabbit hepatocytes metabolize ZEN slowly and mainly into alpha-ZEL, the more uterotrophic metabolite. These last findings are closely related to the higher sensitivity to ZEN estrogenic effects observed in rabbits during the toxicity test involving p.o. administration of the mycotoxin to the animals at 3 dosage levels (0.1, 1, 2 mg/kg body wt).