Back to Search
Start Over
Isoflavonoid-based bone-sparing treatments exert a low activity on reproductive organs and on hepatic metabolism of estradiol in ovariectomized rats.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2007 Oct 15; Vol. 224 (2), pp. 105-15. Date of Electronic Publication: 2007 Jun 30. - Publication Year :
- 2007
-
Abstract
- The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological and molecular analyses on reproductive organs. The impact on the oxidative metabolism of estradiol and on associated cytochrome P450 (CYP) activities was evaluated in liver microsomes. The relative wet weights of both the uterus and the vagina were increased in the equol group, but no significant changes in proliferating cell nuclear antigen or hormone receptor mRNA expression were noticed. In contrast, genistein and daidzein did not induce uterotrophy but caused an overexpression of estrogen receptor alpha mRNA which could correspond to a long-lasting effect of physiological concentrations of estrogens. The hepatic metabolism of estradiol was influenced by daidzein which increased the synthesis of putative mutagenic derivatives. At the same time, genistein favored estrogen 2-hydroxylation, and equol decreased 4-hydroxyestrogen production. Surprisingly, no significant alteration in hepatic CYP activities was detected. Taken together, these results demonstrate that isoflavonoid-based bone-sparing treatments are able to cause side effects on other estrogen-sensitive target organs when given in the long-term.
- Subjects :
- Animals
Bone Density drug effects
Cytochrome P-450 Enzyme System drug effects
Cytochrome P-450 Enzyme System metabolism
Disease Models, Animal
Equol
Female
Gene Expression Regulation drug effects
Genistein pharmacology
Isoflavones pharmacology
Menopause drug effects
Microsomes, Liver metabolism
Organ Size drug effects
Osteoporosis drug therapy
Ovariectomy
Phytoestrogens pharmacology
Proliferating Cell Nuclear Antigen metabolism
Rats
Rats, Wistar
Uterus drug effects
Uterus metabolism
Vagina drug effects
Vagina metabolism
Estradiol metabolism
Genistein adverse effects
Isoflavones adverse effects
Phytoestrogens adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 0041-008X
- Volume :
- 224
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17655901
- Full Text :
- https://doi.org/10.1016/j.taap.2007.06.012