Plasma bioavailability and changes in PBMC gene expression after treatment of ovariectomized rats with a commercial soy supplement

Mohammed A Islam; Guido J E J Hooiveld; Johannes H J van den Berg; Mark V Boekschoten; Vera van der Velpen; Albertinka J Murk; Ivonne M C M Rietjens; F X Rolaf van Leeuwen

doi:10.1016/j.toxrep.2014.12.013

Plasma bioavailability and changes in PBMC gene expression after treatment of ovariectomized rats with a commercial soy supplement

Toxicol Rep. 2015 Jan 2:2:308-321. doi: 10.1016/j.toxrep.2014.12.013. eCollection 2015.

Authors

Mohammed A Islam¹, Guido J E J Hooiveld², Johannes H J van den Berg¹, Mark V Boekschoten², Vera van der Velpen^{2

3}, Albertinka J Murk¹, Ivonne M C M Rietjens¹, F X Rolaf van Leeuwen¹

Affiliations

¹ Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands.
² Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HE Wageningen, The Netherlands.
³ Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.

Abstract

The health effects of soy supplementation in (post)menopausal women are still a controversial issue. The aim of the present study was to establish the effect of the soy isoflavones (SIF) present in a commercially available supplement on ovariectomized rats and to investigate whether these rats would provide an adequate model to predict effects of SIF in (post)menopausal women. Two dose levels (i.e. 2 and 20 mg/kg b.w.) were used to characterize plasma bioavailability, urinary and fecal concentrations of SIF and changes in gene expression in peripheral blood mononuclear cells (PBMC). Animals were dosed at 0 and 48 h and sacrificed 4 h after the last dose. A clear dose dependent increase of SIF concentrations in plasma, urine and feces was observed, together with a strong correlation in changes in gene expression between the two dose groups. All estrogen responsive genes and related biological pathways (BPs) that were affected by the SIF treatment were regulated in both dose groups in the same direction and indicate beneficial effects. However, in general no correlation was found between the changes in gene expression in rat PBMC with those in PBMC of (post)menopausal women exposed to a comparable dose of the same supplement. The outcome of this short-term study in rats indicates that the rat might not be a suitable model to predict effects of SIF in humans. Although the relative exposure period in this rat study is comparable with that of the human study, longer repetitive administration of rats to SIF may be required to draw a final conclusion on the suitability of the rat a model to predict effects of SIF in humans.

Keywords: BPs, biological pathways; Bioavailability; DMSO, dimethyl sulfoxide; Dose effect; E2, estradiol; ECM, extracellular matrix; EREs, estrogen-responsive elements; ERs, estrogen receptors; GSEA, gene set enrichment analysis; Gene expression; HD, high dose; HPLC, high performance liquid chromatography; KEGG, kyoto encyclopedia of genes and genomes; LD, low dose; MDS, multidimensional scaling; NCBI, National Center for Biotechnology Information; PBMC, peripheral blood mononuclear cells; SIF, soy isoflavones; Soy supplementation; Species differences; UPC, universal expression code.