Oxidative metabolism of the mammalian lignans enterolactone and enterodiol by rat, pig, and human liver microsomes.
Hepatic microsomes from aroclor-treated male Wistar rats biotransform enterolactone to 12 metabolites, six of which carry an additional hydroxy group at the aromatic and six at the aliphatic moiety according to HPLC/MS and GC/MS analysis. The aromatic hydroxylation products were identified with the help of synthesized reference compounds as enterolactone monohydroxylated in the para position and in both ortho positions of the original phenolic hydroxy group of either aromatic ring. The synthesis of the reference compounds and their spectroscopic characterization is described. Enterodiol is metabolized by hepatic microsomes from aroclor-treated male rats to three aromatic and four aliphatic monohydroxylated metabolites. Aromatic hydroxylation occurs in the para position and the two ortho positions of the original phenolic hydroxy group. Most of the metabolites of enterolactone and enterodiol were also formed with microsomes from uninduced rat, pig, and human liver, suggesting that oxidative metabolism is a common feature in the disposition of these lignans in the mammalian organism.
Jacobs
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E
Institute of Food Chemistry, Department of Chemistry, University of Karlsruhe, GY-76128 Karlsruhe, Germany.
Metzler
M
M
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D001711:Biotransformation; D020111:Chlorodiphenyl (54% Chlorine) / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004967:Estrogens / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation; D017705:Lignans / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
D004967:Estrogens; D017705:Lignans; D020111:Chlorodiphenyl (54% Chlorine); C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone