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

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.

Les aliments au soja : consommation en France, qualités nutritionnelles et données scientifiques récentes sur la santé

“…S'interroger sur la possibilité d'extrapoler les résultats observés chez le rongeur à l'Homme est donc tout à fait pertinent. Soukup et al (2016) était faible (0,5-1,3 % et 0,5-3,1 % respectivement), tandis qu'elle était plus élevée chez la souris (3,1-26 %), en particulier concernant la daïdzéine. À la différence de l'Homme, tous les rats et les souris se sont montrés producteurs d'équol, quel que soit leur sexe.…”

Exposing the Exposome with Global Metabolomics and Cognitive Computing

“…Consequently, it is possible to directly evaluate the metabolism/toxicokinetics of a toxicant in a specific individual or population sub-group in studies collecting samples at multiple time points, an potentially valuable tool when evaluating for detoxification capacities. A current example of how diverse the metabolism of a xenobiotic may be dependent on species, gender and hormone levels was exemplified by Soukup, et al 31 for GEN and other isoflavones. Hence, we additionally investigated the presence of glucuronide and sulfate conjugates in the pooled serum sample.…”

Metabolomics reveals that dietary xenoestrogens alter cellular metabolism induced by palbociclib/letrozole combination cancer therapy

“…Given the results obtained in this in vitro study it seems not unlikely that the phytoestrogen GEN and the mycoestrogen ZEN may also influence the described PAL+LET combination therapy through their bioactivity in an in vivo scenario. As we aimed to unravel the effects on metabolism on baseline xenoestrogen concentrations realistic in a Western style society (Soukup et al, 2016; Verkasalo et al, 2007; Warth et al, 2013), it is important to note that the described alterations of metabolism, cellular proliferation, and mTOR signaling were caused by rather low concentrations. It is possible that individuals consuming high soy (GEN) or high cereal (ZEN) diets may exceed these concentrations in their plasma.…”