dinoprost and daidzein

The isoflavonoids genistein and daidzein have been shown to have antioxidant activity in vitro, but their effects on in vivo oxidation have not been assessed. The newly described F2-isoprostanes are believed to currently represent the best available marker of in vivo lipid peroxidation. Therefore we have assessed the effects of a 55 mg daily isoflavonoid supplement on urinary F2-isoprostane concentrations in subjects with high-normal blood pressure (BP). A total of 59 subjects completed an 8-week parallel design, randomized, double blind, and placebo-controlled study. F2-isoprostanes, isoflavonoids and creatinine were measured in 24-h urine samples taken at baseline and at the end of the intervention. There were significant increases in urinary excretion of genistein (5.22+/-0.75 mg/day, P < 0.0001) and daidzein (2.53+/-0.43 mg/day, P < 0.0001) in the group taking the isoflavonoid supplement. Creatinine excretion was significantly correlated with F2-isoprostanes at baseline (r = 0.45, P < 0.01). After adjustment for baseline values, there was no significant difference between groups in creatinine adjusted post-intervention F2-isoprostane concentrations (P = 0.74). In addition, changes in genistein and daidzein excretion were not significantly correlated with changes in F2-isoprostanes in the isoflavonoid treatment group. These results are not consistent with the suggestion that the two soy derived isoflavonoids have in vivo antioxidant activity at a level of intake achievable by dietary means and in subjects with high-normal BP.

Topics: Adult; Aged; Antioxidants; Blood Pressure; Creatinine; Dinoprost; Double-Blind Method; Female; Genistein; Humans; Hypertension; Isoflavones; Lipid Peroxidation; Male; Middle Aged

Dietary intake of soy has been linked with decreased cancer risk, and the active compounds in soy that have been identified include the isoflavones genistein and daidzein. Since these compounds have antioxidant properties, we examined levels of oxidative damage in blood of six women and six men before and during soy supplementation using Novasoy tablets. Blood samples were obtained at weekly intervals for 3 weeks from the women taking 50-mg isoflavones once daily and the men taking 50-mg isoflavones twice daily. Plasma levels of genistein and daidzein increased after supplementation with maximal levels occurring at 2 weeks for the women while levels in men kept increasing over the 3 weeks of study. There was wide variation between individuals in the levels of isoflavones achieved. Mean levels of 5-hydroxymethyl-2'-deoxyuridine (5-OHmdU) in DNA from nucleated blood cells decreased after 1 week of supplementation in the women, with a decrease of 47% in mean 5-OHmdU levels after 3 weeks. In men, mean 5-OHmdU levels did not decrease until after 3 weeks of supplementation, at which there was 61% decrease. Mean plasma levels of 8-isoprostanes were not changed appreciably in either men or women. These pilot results suggest that soy isoflavone supplementation decreases levels of oxidative DNA damage in humans, and this may be a mechanism behind the cancer-preventive effects of soy isoflavones.

Topics: Adult; Antineoplastic Agents; Chromatography, High Pressure Liquid; Dietary Supplements; Dinoprost; DNA Damage; Estrogens, Non-Steroidal; F2-Isoprostanes; Female; Genistein; Glycine max; Humans; Immunoenzyme Techniques; Isoflavones; Male; Middle Aged; Oxidative Stress; Phytotherapy; Plant Extracts; Sex Factors; Thymidine; Time Factors

The present study investigated the effect of genistein, daidzein and estradiol on in vitro rat uterine responsiveness to oxytocin (OT) and PGF(2)alpha or luprostiol (L). In a first experiment, animals were either sham-operated (SH; n=5), or ovariectomized (OVX; n=20) and orally treated for three months with either genistein (G; n=5; 10 microg/g BW/d) or daidzein (D; n=5; 10 microg/g BW/d) or 17 alpha-ethinylestradiol (E; n=5; 23 microg/kg BW/d) or untreated (OVX; n=5). At necropsy, the basal uterine tension was lower in OVX, G and D than in SH, the highest value being measured in E. Oxytocin (10(-12); 10(-11) M) or PGF(2)alpha (10(-12); 10(-9) M) induced an increase in SH, but not in OVX, E and G. In D, only the highest doses were efficient. In a second experiment, 20 intact animals were s.c. injected with either genistein (G; n=5; 10 microg/g BW) or daidzein (D; n=5; 10 microg/g BW) or estradiol benzoate (E; n=5; 23 microg/kg BW) or vehicle (C: controls; n=5), and killed 24 h later. In C and E, OT (10(-15) to 10(-10) M) or L (10(-12) to 10(-7) M) stimulated uterine contractile activity in a dose-dependent manner until a maximal level. On the opposite, in G and D, contractile agents (except the highest luprostiol doses) did not stimulate myometrium contractions. Moreover, radioligand binding assays showed that genistein or daidzein inhibited the specific binding of [(3)H] estradiol to the calf uterus estrogen receptor (ER). Therefore, it could be postulated that both genistein and daidzein might bind to the rat uterus ER, inducing either anti-estrogenic or very weak estrogenic effects (depending on the experimental conditions) on in vitro uterine responsiveness to OT and PGF(2)alpha or luprostiol.

Topics: Animals; Dinoprost; Enzyme Inhibitors; Estradiol; Estrogens, Non-Steroidal; Female; Genistein; In Vitro Techniques; Isoflavones; Organ Size; Ovariectomy; Oxytocics; Oxytocin; Prostaglandins F, Synthetic; Random Allocation; Rats; Rats, Wistar; Receptors, Estrogen; Uterine Contraction; Uterus

Some of the isoflavonoids present in human diet as well as in urine are expected to exert biologic effects as they have been reported to bind to estrogen receptors and to be estrogenic in other species. This report describes the in vitro assessment of estrogenic effects of isoflavonoids using human endometrial cells and tissue. The relative estrogenic potencies (EC50 values) of estradiol, 3 dietary isoflavonoids (coumestrol, genistein and daidzein) and one of their metabolites (equol), were estimated by using a recently developed multiwell plate in vitro bioassay based on the estrogen-specific enhancement of alkaline phosphatase (AlkP) activity in human endometrial adenocarcinoma cells of the Ishikawa-Var I line. The maximal AlkP activity elicited by the isoflavonoids tested was as high as that achieved with estradiol and their effects were suppressed by the antiestrogens 4-hydroxytamoxifen and ICI 164,384. These results indicate that estradiol and the isoflavonoids exert their effects on AlkP by similar interactions with the estrogen receptor, with potencies depending on binding affinities. The estrogenic effect of equol was confirmed by another in vitro bioassay, based on the estrogen-stimulated enhancement of prostaglandin F2 alpha output by fragments of human secretory endometrium.

Topics: Adenocarcinoma; Alkaline Phosphatase; Biological Assay; Chromans; Coumestrol; Dinoprost; Endometrial Neoplasms; Endometrium; Equol; Estradiol; Female; Genistein; Humans; Isoflavones; Polyunsaturated Alkamides; Tamoxifen; Tumor Cells, Cultured