The present study investigated the involvement of UDP-glucuronosyltransferase and sulfotransferase in the extensive liver and intestinal first-pass glucuronidation and sulfation of flavones in both mice and humans. Seven structurally similar mono- and di-hydroxyflavones were chosen as model compounds. Human liver, C57 mouse liver and intestinal S9 fraction, as well as C57 intestinal perfusion model were used. In human and C57 mouse, all selected flavones were found to be glucuronidated with the highest rates at the 7-OH group. In contrast, flavones with 3-OH group were not sulfated at all. Both glucuronidation and sulfation preferred 4'- and 7-OH in human and mouse in vitro and in situ. There were differences in glucuronidation and sulfation in human and mouse observed for all flavones and it is based on substitutional positions of the hydroxyl groups. The S9 fractions could accurately model glucuronidation (as the slope of correlation curve was 0.7988 for those flavones with 4'- or 7-OH) and sulfation (as the slope of correlation curve was 0.9834) in situ. Conclusively, the sulfation and glucuronidation of the flavones was regiospecific- and speciesdependent. Sulfation and glucuronidation in the mouse intestine in vitro were correlated well with those in situ.
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