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

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.

Soy supplementation: Impact on gene expression in different tissues of ovariectomized rats and evaluation of the rat model to predict (post)menopausal health effect

“…In Fig. 2 the gene expression patterns in PBMC of the present rat study were compared to those obtained in the short-term rat study [ 18 ]. Only 145 genes were significantly regulated in both data sets (data not shown) of which fifteen marker genes were identified to be highly correlated (deviation value 0 to ±10) and their gene expression was significantly changed in the same direction (increased or decreased) in both studies.…”

“…8 week exposure) and from the group exposed to the same dose (i.e. 2 mg soy isoflavones/kg bw per day) in the short-term (2 days) rat study [ 18 ]. Each dot represents the t-value of a single gene and the highlighted dots ( ♦ ) indicate the highly correlated genes.…”

“…Secondly, the use of an inbred strain will minimize the background noise in micro array analysis. Thirdly, for reasons of comparison, we used the same strain of rats as for the short-term study and measured PBMC gene expression; this enabled comparison of PBMC gene expression after long term exposure (present study) and short term exposure [ 18 ].…”

“…This short-term study, in which rats from the same strain (i.e. ovariectomized F344) were exposed to a similar soy isoflavone supplement, and also PBMC were collected and studied by microarray analysis, was mainly designed for quantification of the bioavailability of soy isoflavone [ 18 ].…”

“…breast, uterus and sternum tissues) and non-target (PBMC, adipose and liver tissues) tissues of ovariectomized female F344 rats exposed to a commercially available soy supplement for eight weeks in an oral dose which, on a kg bw base, is similar as the recommended dose for humans. In addition, the changes in gene expression in PBMC in the current study were compared with those of a previously reported short-term rat study [ 18 ]. Finally a cross-species comparison of changes in gene expression in PBMC and adipose tissues among ovariectomized rats and (post)menopausal women was carried out to compare the effects of soy isoflavone supplementation in rats with those observed in (post)menopausal human volunteers.…”