In vitro and in vivo metabolism of the soy isoflavone glycitein.

Glycitein (GLY) is a major isoflavone of soy germ which is used as a functional ingredient to enrich foods with isoflavones as well as a component of soy supplements. Since data on the metabolism of GLY are incomplete, the in vitro phase I metabolism of GLY using rat liver microsomes, human liver microsomes (HLM), as well as human fecal flora was investigated. Furthermore, the in vivo metabolism has been studied after administration of GLY to Sprague-Dawley rats. The identification of the formed metabolites has been elucidated using HPLC/DAD, HPLC/API-ES MS, GC/MS, as well as reference compounds. With respect to the phase I metabolism, GLY has been converted to ten metabolites by liver microsomes of Aroclor-induced Wistar rats with 8-hydroxy(OH)-GLY as the main metabolite. HLM converted GLY to six metabolites with 8-OH-GLY and 6-OH-daidzein (DAI) being the major products. No sex-related differences were observed in each system. Intestinal metabolism of GLY led to four metabolites with 6-OH-DAI as the main product. The in vivo metabolism in rat urine after single-dose administration of GLY resulted in the identification of three oxidative and two bacterial metabolites as well as the demethylation product 6-OH-DAI as the main metabolite.

Selective metabolism of E-3,4-bis(4-ethylphenyl)hex-3-ene in rat liver microsomes.

The synthetic stilbene derivative E-3,4-bis(4-ethylphenyl)hex-3-ene (E-DE-BPH) has been proposed as a potential anticancer drug with a new mode of action. We report here on the in vitro metabolism of E-DE-BPH in liver microsomes of rats and pigs. The formation of five metabolites, which could be separated on a reverse-phase HPLC column with UV detection, was observed in microsomal incubations. To facilitate the structural identification of these metabolites, two different deuterium-labeled forms of E-DE-BPH were synthesized. By comparing the mass spectra obtained for the metabolites of unlabeled E-DE-BPH and of the two deuterated forms, it could be demonstrated that E-DE-BPH was oxidized by liver microsomes exclusively at the benzylic positions of the molecule. The major metabolite was identified as E-3-(4-(1-hydroxyethyl)phenyl)-4-(4-ethylphenyl)hex-3-ene. Four minor metabolites were formed from the major metabolite, either by hydroxylation at the other benzylic position to yield a bishydroxylated metabolite, or by oxidation of the hydroxyl group to form E-3-(4-acetylphenyl)-4-(4-ethylphenyl)hex-3-ene. The latter compound was also obtained by chemical oxidation of the monohydroxylated metabolite of E-DE-BPH. Since no products containing hydroxyl groups at the aromatic rings or at other aliphatic sites of the molecule were detected, a surprisingly selective oxidative metabolism of E-DE-BPH appears to occur with rat and pig liver microsomes.