TY - JOUR
T1 - Plasma bioavailability and changes in PBMC gene expression after treatment of ovariectomized rats with a commercial soy supplement
AU - Islam, Mohammed A.
AU - Hooiveld, Guido J. E. J.
AU - van den Berg, Johannes H. J.
AU - Boekschoten, Mark V.
AU - van der Velpen, Vera
AU - Murk, Albertinka J.
AU - Rietjens, Ivonne M. C. M.
AU - van Leeuwen, F. X. Rolaf
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Soy supplementation
KW - bioavailability
KW - gene expression
KW - does effect
KW - species differences
UR - http://www.scopus.com/inward/record.url?scp=84921488229&partnerID=8YFLogxK
U2 - 10.1016/j.toxrep.2014.12.013
DO - 10.1016/j.toxrep.2014.12.013
M3 - Article
AN - SCOPUS:84921488229
VL - 2
SP - 308
EP - 321
JO - Toxicology Reports
JF - Toxicology Reports
SN - 2214-7500
ER -