Phase II metabolism of the soy isoflavones genistein and daidzein in humans, rats and mice: a cross-species and sex comparison

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Soy isoflavones (IF) are in the focus of biomedical research since more than two decades. To assess their bioactivity, IF are investigated in rats and mice as a model. As the biological activity of IF is affected by their biotransformation, our aim was to comprehensively compare the conjugative and microbial metabolism of daidzein and genistein in adult humans, rats and mice of both sexes. One identical soy extract and a validated LC-MS method were used for all studies. We detected considerable differences between the three species. In rats and mice, sex-specific differences were observed in addition. The major plasma phase II metabolites in humans were the 7-sulfo-4'-glucuronides (39-49 %) and, in case of genistein, also the diglucuronide (34 %), whereas in mice monosulfates (33-41 %) and monoglucuronides (30-40 %) predominated. In male rats the disulfates (23-62 %) and 7-sulfo-4'-glucuronides (19-54 %) were predominant, while in female rats the 7-glucuronides (81-93 %) exhibited highest concentrations. The portion of aglycones was low in humans (0.5-1.3 %) and rats (0.5-3.1 %) but comparatively high in mice (3.1-26.0 %), especially in the case of daidzein. Furthermore, substantial differences were observed between daidzein and genistein metabolism. In contrast to humans, all rats and mice were equol producer, independent of their sex. In conclusion, there are marked differences between humans, rats and mice in the profile of major metabolites following IF phase II metabolism. These differences may contribute to resolve inconsistencies in results concerning the bioactivity of IF and should be considered when applying findings of animal studies to humans, e.g., for risk assessment.

Details

Original languageEnglish
Pages (from-to)1335-1347
Number of pages13
JournalArchives of Toxicology
Volume90
Issue number6
Publication statusPublished - Jun 2016
Peer-reviewedYes

External IDs

PubMed 26838042
Scopus 84969513713

Keywords

Keywords

  • Adult, Animals, Biotransformation, Chromatography, High Pressure Liquid, Female, Genistein/blood, Humans, Isoflavones/blood, Limit of Detection, Male, Mass Spectrometry, Metabolic Detoxication, Phase II, Mice, Inbred BALB C, Middle Aged, Postmenopause/blood, Rats, Wistar, Sex Factors, Soybeans/chemistry, Species Specificity