Scope: Zearalenone (ZEN) and α-zearalanol (α-ZAL, zeranol) were studied in differentiated Caco-2 cells and in the Caco-2 Millicell® system in vitro to simulate their in vivo intestinal absorption and metabolism in humans.
Methods and results: In addition to metabolic reduction/oxidation, extensive conjugation with glucuronic acid and sulfate of the parent compounds and their phase I metabolites was observed. The positional isomers of the glucuronides and sulfates were unambiguously identified: Sulfonation occurred specifically at the 14-hydroxyl group, whereas glucuronidation was less specific and, in addition to the preferred 14-hydroxyl group, involved the 16- and 7-hydroxyl groups. Using the Caco-2 Millicell® system, an efficient transfer of the glucuronides and sulfates of ZEN and α-ZAL and their phase I metabolites into both the basolateral and the apical compartment was observed after apical administration. The apparent permeability coefficients (Papp values) of ZEN, α-ZAL and the ZEN metabolite α-zearalenol were determined, using an initial apical concentration of 20 μM and a permeation time of 1 h.
Conclusion: According to the Papp values, the three compounds are expected to be extensively and rapidly absorbed from the intestinal lumen in vivo and reach the portal blood both as aglycones and as glucuronide and sulfate conjugates in humans.