Plant Estrogens Research Articles

Phytoestrogenic Isoflavones Daidzein and Genistein Reduce Glucose‐Toxicity‐Induced Cardiac Contractile Dysfunction in Ventricular Myocytes

Epidemiological evidence suggests a reduction in the incidence of coronary heart disease, cancer and osteoporosis in populations with a high dietary intake of plant estrogen or phytoestrogen. The clinical benefit of phytoestrogens in cereals, vegetables and medicinal plants is attracting increasing attention for the general public. In the present study, we examined the effect of phytoestrogenic isoflavones daidzein and genistein on glucose toxicity‐induced cardiac mechanical malfunction simulating diabetic cardiomyopathy. Adult rat ventricular myocytes were isolated and maintained for 24 hours in normal (NG, 5.5 mM) or high glucose (HG, 25.5 mM) medium in the absence or presence of isoflavones daidzein (50 µM) or genistein (20 µM). Cardiac contractile indices were evaluated using an IonOptix® MyoCam system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time‐to‐PS (TPS) and time‐to‐90% relengthening (TR90). Myocytes maintained in HG medium displayed altered mechanical function simulating in vivo diabetes including reduced PS, ± dL/dt and prolonged TR90 associated with normal TPS compared to those from NG myocytes. Interestingly, these HG‐induced mechanical dysfunctions were abolished by co‐incubation of daidzein or genistein. However, daidzein but not genistein itself depressed PS in NG myocytes. Neither daidzein nor genistein affected any other mechanical parameters tested in NG myocytes. Collectively, these data suggest that the phytoestrogenic isoflavones daidzein and genistein may reduce glucose toxicity‐induced cardiac mechanical dysfunction and thus possess therapeutic potential against diabetes‐associated cardiac defects.

Soy and bone. Where do we stand?

Interest in the use of plant estrogens (phytoestrogens) to attenuate postmenopausal bone loss has increased during the past 10 years as healthcare consumers, practitioners, and scientists have searched for alternative treatments to the use of hormone replacement therapy. Promising research has emerged regarding the potential benefit of increased consumption of phytoestrogens, primarily from dietary soy products. Dietary phytoestrogens, primarily isoflavones found in soy foods, may alter bone turnover in postmenopausal women by decreasing bone resorption and increasing bone formation.

Menopausal hormone therapy informed consent

A little over a year ago now, the large hormone therapy clinical trial of the Women’s Health Initiative came to an abrupt halt. The publication of the results rocked the medical community and our patients because a class of drugs once thought to be associated overwhelmingly with benefit was found to cause more harm than good. Now doctors have the dilemma of how to inform patients of the results of the Women’s Health Initiative in a way that will help them make the best decision for themselves of whether they should use of these agents for hot flashes, night sweats, vaginal dryness, or prevention of osteoporosis. In the thousands of daily conversations on this topic, the scenario used to look like this: The patient came to the office asking questions about menopause. When the practitioner determined the patient was going through the menopausal transition, the doctor wrote a prescription for hormone pills or patches, saying they would address her concerns by replacing the hormones her body used to make. They would abolish her hot flashes, slow her bone loss, and reduce her risk of a heart attack. The patient asked if the pills caused breast cancer. Probably in some women, the doctor would acknowledge, but argued that the benefits to the heart and bones were worth taking the chance. Now the patient comes to the office and asks about the confusing information she has been reading on the increased risk of heart attack, strokes, blood clots, and dementia with hormone use. The doctor acknowledges the information has changed and is very important, but the decision to use or not to use hormones is up to her. She has menopausal symptoms and wants a solution. However, she is looking for something safe that does not cause more problems than it solves.

More Evidence That Plant Estrogens Don't Reduce Hot Flashes

In the wake of findings from the Women's Health Initiative (Journal Watch Women's Health Aug 7 2002 ), the literature is teeming with studies designed

Evidence for cell-specific changes with age in expression of oestrogen receptor (ER) alpha and beta in bone fractures from men and women.

Oestrogen is recognized as important for maintaining bone mass in men and women. Oestrogen receptor (ER) alpha and the recently described ER-beta are both expressed in bone cells, but have different affinities for oestrogen agonists and plant oestrogens, which could be important in developing treatments for bone loss in both men and women. It is unclear, however, which isoform predominates in bone; cell type and age may influence their relative expression. The present study has compared ER-alpha and ER-beta expression in serial sections of human fracture callus from males (n = 19, age range 5-72 years) and females (n = 15, age range 3-86 years) by indirect immunoperoxidase. Fracture callus was used as it can be readily obtained from individuals over a wide age range and contains a variety of bone cells. Antibody specificity was confirmed by western blotting and comparison of immunoreactivity in sections of breast tumour and benign prostate hyperplasia. No gender difference in ER expression was found in bone from individuals less than 40 years old. Proliferative chondrocytes were positive for both isoforms, but few larger hypertrophic cells were immunoreactive. ER-alpha and ER-beta were co-expressed in osteoclasts, suggesting that oestrogen may act directly on these cells. Osteoblasts, osteocytes, and mesenchymal cells also expressed both isoforms. In women over 40 years of age, however, relatively fewer biopsies contained osteocytes positive for ER-alpha and ER-beta. Likewise, the proportions of osteoblasts and mesenchymal cells expressing ER-beta were reduced but ER-alpha remained unaffected. In contrast, in men over 40 years, only the proportion of biopsies containing ER-beta-positive mesenchymal cells was lower. In these older men and women, ER-alpha and ER-beta expression was retained by the small proliferative chondrocytes. These results demonstrate that gender, age, and cell type are important determinants of ER isoform expression in skeletal cells.

Lipoprotein-associated estrogens.

The discovery of a family of hormonal steroids esterified with fatty acid has raised questions concerning their physiologic role. Because of their water-insolubility these compounds are present in the circulation only as components of lipoprotein particles. Current evidence supports the hypothesis that estrogen esterification is catalyzed by lecithin:cholesterol acyltransfearse associated with HDL. In addition, recent results indicate that estradiol esters are transferred from HDL to LDL particles in a cholesteryl ester transfer protein (CETP)-associated process. The studies now focus on the various possible physiologic roles proposed for these hormone derivatives, (1) functioning as fat-soluble antioxidants incorporated in lipoproteins rendering protection against oxidation of these particles, (2) providing a mechanism for hormonal storage in lipoproteins and fat tissues, (3) providing a novel hormone transport system using lipoprotein as carriers and lipoprotein receptors for entry into cells. Quantitative methods of determination of estradiol fatty acid esters in human body fluids have been developed. Preliminary studies suggest that diet-derived plant estrogens may also form fat-soluble derivatives which become incorporated in lipoproteins.

A Case-Control Study of Dietary Phytoestrogens and Testicular Cancer Risk

A few dietary studies have found elevated testicular cancer risks for higher red meat, fat, and milk intakes and lower intakes of fruits, vegetables, and fiber. Because hormonal modulation by dietary intake of plant estrogens could affect risk of testicular cancer, we chose to explore the possible relationship between dietary phytoestrogens and testicular cancer. We conducted a hospital-based case-control study of 159 testicular cancer cases diagnosed between 1990 and 1996 and 136 adult friend-matched controls at the University of Texas M. D. Anderson Cancer Center. Amounts of phytoestrogenic compounds in foods were added to the National Cancer Institute's DietSys program and then grouped into prelignans, lignans, flavonoids, isoflavonoids, phytosterols, and coumestrol for statistical analysis, expressed per 1,000 kcal. The results of multivariate logistic regression analysis showed, after adjustment for age, education, income, ethnicity, cryptorchidism, body mass index, baldness unrelated to therapy, severe acne in adolescence, early puberty, daily fiber and fat intake, and total daily calories, no discernable monotonic increased or decreased risk estimates across quartiles of phytoestrogen intake. A U-shaped pattern was observed for lignans and coumestrol. Further evaluation of this pattern by cubic spline parameterization did fit the data, but the data were also consistent with no effect. This hypothesis-generating study does not support the premise that dietary phytoestrogens increase or decrease testicular cancer risk in young men.

Is exposure to endocrine disrupting compounds during fetal/post-natal development affecting the reproductive potential of farm animals?

Concerns have been raised about the potential adverse effects on reproductive health and immune status of farm animals following exposure to a range of natural and synthetic environmental compounds that disrupt normal hormonal actions. These compounds range from natural plant oestrogens (e.g. genistein, coumesterol) and mycoestrogens (e.g. Aflatoxins, zearalenone) to growth promoting pharmaceuticals (e.g. trenbolone acetate, melengastrol acetate) to chemicals spread in water, sewage sludge or the atmosphere such as detergents and surfactants (e.g. octylphenol, nonylphenol), plastics (e.g. bisphenol-A, phthalates), pesticides (e.g. methoxychlor, dieldrin, DDT) and industrial chemicals (e.g. PCB, TCDD). These compounds are commonly termed ‘endocrine disrupting compounds’ (EDCs) or ‘endocrine disruptors’ due to their ability to act as either hormone agonists or antagonists or the ability to disrupt hormone synthesis, storage or metabolism. A similar group of compounds are called ‘immunotoxicants’ and are thought to affect the immune system mainly by disrupting B and T cell homeostasis. As more studies are performed it is becoming clear that many compounds can directly or indirectly affect both the endocrine and immune systems. The susceptibility of target tissues is related to the stage of development, the cumulative exposure dose and the immune status of the individual. While some of the effects of the EDCs on the endocrine and immune systems are quite distinct, many are subtle and identifying the causative agent from the vast array of environmental challenges including EDCs, nutrition, temperature, etc. can be problematic. Identifying the causative agent is confounded by the possibility that effects that are observed in the adult may be due to exposure to EDCs during fetal life. This has major implications for the determination of universal end-point measurements to assess exposure to EDCs in farm animals.

Phytoöstrogene und Brustkrebs - senken Pflanzenöstrogene das Risiko?

Ernährungsfaktoren haben einen signifikanten modulierenden Einfluss auf das Brustkrebsrisiko von Frauen. Epidemiologische Ländervergleichsstudien legen nahe, dass Soja, unraffinierte Korn- und Samenprodukte sowie Gemüse das Brustkrebsrisiko senken könnten. Asiatische Frauen, die sich traditionell und bevorzugt phytoöstrogenreich ernähren, haben eine niedrige Brustkrebsinzidenz und -mortalität. In Migrationsstudien fanden sich niedrige Brustkrebsrisiken bei weiblichen Erste-Generation-Migrantinnen mit einer Kindheit in ihrem asiatischen Heimatland, jedoch schon die zweite Generation verlor mit zunehmendem „westlichen“ Ernährungs- und Lebensstil diesen Schutz.

THE INFLUENCE OF COUMESTROL, ZEARALENONE, AND GENISTEIN ADMINISTRATION ON INSULIN RECEPTORS AND INSULIN SECRETION IN OVARIECTOMIZED RATS

ABSTRACTThe influence of phytoestrogens (genistein and coumestrol) and mycoestrogen (zearalenone) on insulin secretion, liver insulin receptors and some aspects of lipid and carbohydrate metabolism were investigated in this study. Ovariectomized rats were injected s.c. with the above mentioned compounds in the amount of 1 mg for three days. Coumestrol and zearalenone caused a significant increase in uterus weight, similar to the effects observed after estrone action, while this effect was not observed after the genistein injection. Blood insulin level was not changed after phyto- or mycoestrogen treatment. However, coumestrol and genistein significantly decreased the binding capacity of liver insulin receptors. These changes corresponded with alterations in glucose and free fatty acids profiles in blood, as well as with glycogen content in liver. The effects observed after genistein and coumestrol injections differed from those noticed in rats treated with zearalenone or estrone. On the basis of these results we conclude that metabolic effects of high doses of coumestrol and genistein in ovariectomized rats are partly mediated by changes in insulin sensitivity of the liver and that the action of plant estrogens on metabolism is, at least to the some degree, independent of their estrogen activity.

Neurobehavioral actions of coumestrol and related isoflavonoids in rodents

Isoflavonoids are plant estrogens that are increasingly advocated as a natural alternative to estrogen replacement therapy (ERT) and are available as dietary supplements. As weak estrogen agonists/antagonists with a range of other enzymatic activities, the isoflavonoids provide a useful model for the actions of endocrine disruptors. This paper reviews the responses of rodents to diets containing coumestrol or an isoflavone supplement in comparison to animals fed the phytoestrogen-free AIN76A diet. Neural mechanisms were investigated by examining isoflavonoid effects on ERα-dependent (regulation of oxytocin receptor [OTR] binding in the ventromedial nucleus of the hypothalamus [VMN]) and ERβ-dependent (regulation of ERβ mRNA in the paraventricular nucleus [PVN]) endpoints. Activational as well as organizational effects on sexual behavior and gonadotropin secretion were observed for coumestrol. Treatment of rat dams with a 100-ppm coumestrol diet from birth to postnatal day (PND) 21 induced premature anovulation in female offspring, and treatment from birth to PND 10 suppressed sexual behavior in male offspring. One-week treatment of ovariectomized (OVX) female rats with the same coumestrol diet increased ERβ mRNA expression in the PVN, an effect opposite to that of estradiol. Ten days of treatment with a 200-ppm coumestrol diet increased LH secretion in OVX wild-type mice, an effect opposite to the normal negative feedback effects of estradiol. No effects were observed in ERα knockout (ERαKO)-OVX females, indicating that coumestrol's action on LH was mediated through ERα. Similar activational effects were observed for the isoflavone diet. The lordotic response to estrogen was significantly reduced by 2 days of treatment of OVX adult females with an isoflavone diet providing 13 ppm genistein and 33 ppm daidzein. One week of treatment with the same isoflavone diet produced an effect opposite to that of estradiol in the PVN, increasing ERβ mRNA expression above control levels. These investigations show that, in spite of their preferential affinity for ERβ, isoflavonoids act through both ERα and ERβ. Moreover, their neurobehavioral actions were antiestrogenic, either antagonizing or producing an action in opposition to that of estradiol. This work demonstrates that even small, physiologically relevant exposure levels can alter estrogen-dependent gene expression in the brain and complex behavior.

Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats.

In women, arterial pressure generally increases after menopause, but several studies suggest that women who eat large amounts of plant estrogens (phytoestrogens) experience a slower rise in the incidence of postmenopausal hypertension. This suggests that both ovarian hormones (principally estrogen) and phytoestrogens may protect at least some women from hypertension. The present study tests the hypothesis that phytoestrogens blunt hypertension in estrogen-depleted female spontaneously hypertensive rats (SHR). Three-week-old ovariectomized SHR were fed one of four diets that contained basal (0.6%) or high (8%) NaCl with or without dietary phytoestrogens for 9 wk. In SHR on the basal NaCl diet, arterial pressure was unaffected by the removal of dietary phytoestrogens. In contrast, in SHR on the high-NaCl diet, arterial pressure was significantly higher in rats on the phytoestrogen-free (204 +/- 4 mmHg) compared with the phytoestrogen-replete (153 +/- 4 mmHg) diet. Ganglionic blockade resulted in reductions in arterial pressure that were directly related to the dietary NaCl-induced increases in arterial pressure. Together, these data indicate that dietary phytoestrogens protect ovariectomized female SHR from dietary NaCl-sensitive hypertension and that the sympathetic nervous system plays an important role in this effect. Furthermore, these results demonstrate that dietary phytoestrogens can have a major impact on the interpretation of studies into the physiological role of estrogen in females.

Soya isoflavones: a new and promising ingredient for the health foods sector

Isoflavones are phytoestrogens, they have a structural/functional similarity to human estrogen and have been consumed by humans world-wide throughout history. Of all plant estrogens, soy isoflavones have been studied most. Because of the extensive consumption of soy-foods in Asia and Japan, there is reasonably knowledge on long-term safety aspects, as well as on possible interactions between soy isoflavone consumption and disease prevention. In Asian countries, soy-isoflavone intake is estimated to range from 20–100 mg/day. The Western population, however, consumes much less. A comparison of populations on a high isoflavone intake with the normal Western population highlights a lower mortality rate and lower incidence of heart disease, type II diabetes, osteoporosis and certain cancers. If it is true that regular consumption of isoflavones may help to reduce the risk of certain diseases, then this is a good reason to educate people to consume isoflavone-rich foods. Based on the availability of extracted soy isoflavones it is now possible to study the effect on relevant bio-markers in controlled clinical trials. A confirmation of safety and efficacy is important for the establishment and legal/public acceptance of compound related health claims. Recent studies on the effect of isoflavones on heart health, bone health and post-menopausal symptoms, indicate positive effects that are highly attractive to the functional foods market. Further independent studies are required to substantiate health benefit claims.

Fat reduction to prevent prostate cancer: waiting for more evidence?

Complementary medicine has become an important area of interest for patients and researchers around the world. The utilization of some of these therapies by many individuals makes it imperative to understand whether they have any role in treatment of cancer or other diseases. Some of such therapies may play a role in the prevention of prostate cancer. Clinical trials are addressing this issue, and whether these products could also improve prognosis of prostate cancer. That dietary fat reduction may help to prevent prostate cancer is supported by numerous case-control studies reported over the past several decades, but recent prospective studies suggest that the impact of fat reduction in this regard may not be great. Clinicians should be careful not to suggest such a benefit until more research provides a better picture of the situation. Breast cancer is probably the best example of why more research into dietary changes for reduction in cancer risk is needed. Once believed to play a significant role, recent prospective studies suggest that dietary fat reduction may have little effect on breast cancer prevention, although some interesting insights have been gained with regard to the method of meat preparation and the influence of genetics. Fat reduction, together with soy products or other plant estrogen foods, may have a symbiotic relationship. Numerous healthy lifestyle changes incorporated and practiced at one time (healthy diet, attainment and maintenance of normal weight, soy consumption, among others) may hold some promise in the area of cancer prevention. In the meantime any healthy lifestyle or dietary change should be encouraged, because it may reduce the risk of cardiovascular disease, which is still the number one cause of mortality. It is also an important cause of morbidity and mortality in cancer patients. Regardless, complementary medicine should probably be discussed with any patient who is initiating or undergoing conventional treatment, because of the cardiovascular benefits and overall potential impact on all-cause mortality. Whether such therapies impact on prostate carcinoma remains to be determined through additional prospective investigations.

Dietary Estrogen Protects Against NaCl-Sensitive Hypertension in Estrogen-Depleted Female Spontaneously Hypertensive Rats.

P169 In male spontaneously hypertensive rats (SHR) a high NaCl diet produces a rapid and sustained increase in hypertension. In contrast, in female SHR a high NaCl diet causes only a small, transient increase in arterial pressure. Elimination of most endogenous estrogen (via ovariectomy) produces mild NaCl-sensitive hypertension in female SHR, but simultaneous ovariectomy and elimination of exogenous dietary plant estrogens (phytoestrogens) nearly quadruples the hypertensive effect of the high NaCl diet, although phytoestrogen removal has a negligible effect on blood pressure in SHR fed a basal NaCl diet. This suggests that phytoestrogens (particularly genistein, the primary dietary phytoestrogen) protect ovariectomized female SHR from NaCl-sensitive hypertension. However, other reports suggest that the beneficial effects of phytoestrogens may only be present when genistein is combined with a high soy diet. The present study tests the hypothesis that genistein can independently reduce NaCl-sensitive hypertension in estrogen-depleted female SHR. Female SHR were ovariectomized at 3 weeks of age and placed on one of four casein-based, non-soy containing, diets (AIN-76A), i.e., a high (8%) or basal (0.6%) NaCl diet with or without genistein (0.06%; the approximate phytoestrogen concentration in the diet) added to the diet. After 5 weeks, femoral arterial catheters were implanted and 3 days later arterial pressures were recorded from all rats. The high NaCl diet increased arterial pressure by 68 ± 6 mm Hg in the phytoestrogen-free SHR, but produced only a 17 ± 5 mm Hg rise in arterial pressure in the genistein-supplemented group (similar to the rise previously observed in ovariectomized SHR fed a normal high NaCl diet). These results demonstrate that dietary genistein reduces NaCl-sensitive hypertension in ovariectomized female SHR. This work was supported by NHLBI Grant HL-37722.

Dietary Estrogen Protects Against NaCl-Sensitive Hypertension in Estrogen-Depleted Female Spontaneously Hypertensive Rats.

P169 In male spontaneously hypertensive rats (SHR) a high NaCl diet produces a rapid and sustained increase in hypertension. In contrast, in female SHR a high NaCl diet causes only a small, transient increase in arterial pressure. Elimination of most endogenous estrogen (via ovariectomy) produces mild NaCl-sensitive hypertension in female SHR, but simultaneous ovariectomy and elimination of exogenous dietary plant estrogens (phytoestrogens) nearly quadruples the hypertensive effect of the high NaCl diet, although phytoestrogen removal has a negligible effect on blood pressure in SHR fed a basal NaCl diet. This suggests that phytoestrogens (particularly genistein, the primary dietary phytoestrogen) protect ovariectomized female SHR from NaCl-sensitive hypertension. However, other reports suggest that the beneficial effects of phytoestrogens may only be present when genistein is combined with a high soy diet. The present study tests the hypothesis that genistein can independently reduce NaCl-sensitive hypertension in estrogen-depleted female SHR. Female SHR were ovariectomized at 3 weeks of age and placed on one of four casein-based, non-soy containing, diets (AIN-76A), i.e., a high (8%) or basal (0.6%) NaCl diet with or without genistein (0.06%; the approximate phytoestrogen concentration in the diet) added to the diet. After 5 weeks, femoral arterial catheters were implanted and 3 days later arterial pressures were recorded from all rats. The high NaCl diet increased arterial pressure by 68 ± 6 mm Hg in the phytoestrogen-free SHR, but produced only a 17 ± 5 mm Hg rise in arterial pressure in the genistein-supplemented group (similar to the rise previously observed in ovariectomized SHR fed a normal high NaCl diet). These results demonstrate that dietary genistein reduces NaCl-sensitive hypertension in ovariectomized female SHR. This work was supported by NHLBI Grant HL-37722.

Xenoestrogênios: o exemplo do bisfenol-A

Evidências acumuladas indicam que a saúde dos seres humanos, animais e espécies selvagens pode sofrer conseqüências adversas da exposição a produtos químicos presentes no meio ambiente e que interagem com o sistema endócrino, tais como bifenilas policloradas, dioxinas, estrogênios de ocorrência natural e sintéticos. Por outro lado, permanecem incertezas científicas com respeito aos dados relatados e, também, quanto à hipótese de haver níveis suficientemente elevados de exposição a estes agentes, a ponto de exercer efeito estrogênico generalizado sobre a população. Este trabalho revisa os principais tópicos relacionados a um dos xenoestrogênios que vem sendo mais recentemente estudado: o Bisfenol A (BFA), um monômero de plástico poli-carbonato, com pouca homologia estrutural com o estradiol (E2) mas semelhante ao dietilestilbestrol (DES), hexestriol e componente bisfenólico do tamoxifeno. O presente trabalho comenta e analisa criticamente os efeitos do BFA sobre o trato reprodutivo e função lactotrófica em animais de experimentação, à luz das informações disponíveis e experiência do grupo nesta área, e recomenda algumas necessidades de pesquisa.

Phytoestrogens do not influence lipoprotein levels or endothelial function in healthy, postmenopausal women

Plant estrogen or phytoestrogens (PE) are increasingly consumed for the purposes of menopause symptom relief and prevention of cardiovascular and other diseases. The objective of this study was to evaluate the effects of PE on plasma lipids and lipoproteins and on endothelial function. Twenty healthy, postmenopausal women, 50 to 70 years old, and with evidence of endothelial dysfunction, were treated with a soybean PE tablet of 80 mg/day of isoflavones. Endothelial function was assessed noninvasively using brachial ultrasound. A double-blind, placebo-controlled, randomized crossover design was employed. After 3 weeks stabilization on a standard fat-reduced diet, subjects received PE or placebo for 8 weeks in random order, separated by a washout period of 8 weeks. Compared with placebo, there were no significant effects of PE on blood pressure and plasma lipid or lipoprotein concentrations. Flow-mediated endothelium-dependent dilation (FMD) in response to reactive hyperemia was not significantly changed by PE ingestion (3.3 ± 0.7% on placebo vs 4.1 ± 0.7% on PE, p >0.4). Variation in FMD was not correlated with change in plasma isoflavone concentration (r = −0.09, p >0.7). Glyceryl trinitrate endothelium-independent dilation was not significantly changed with PE (15.9 ± 1.3% vs 13.7 ± 1.2%, p >0.1). These results fail to show a significant impact of medium-term supplementation with 80 mg/day of isoflavones on lipid and lipoprotein levels or on endothelial function in healthy, postmenopausal women.

Cardioprotection by the phytoestrogen genistein in experimental myocardial ischaemia-reperfusion injury.

1. Soybean phytoestrogens have no oestrogen agonist effects on the reproductive system and therefore it is reasonable to explore the potential of these naturally occurring plant oestrogens in the cardiovascular pathology. We therefore investigated the effects of genistein in a rat model of myocardial ischaemia-reperfusion injury. 2. Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham operated rats were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK), serum and macrophage Tumour Necrosis Factor-alpha (TNF-alpha), cardiac intercellular adhesion molecule-1 (ICAM-1) immunostaining, cardiac mRNA for ICAM-1 evaluated by the means of reverse transcriptase polymerase chain reaction (RT - PCR), ventricular arrhythmias and myocardial contractility (left ventricle dP/dt(max)) were evaluated. 3. Myocardial ischaemia and reperfusion in untreated rats produced marked myocardial necrosis, increased serum CPK activity and MPO activity both in the area-at-risk and in the necrotic area, reduced myocardial contractility, caused ventricular arrhythmias and induced a marked increase in serum and macrophage TNF-alpha. Furthermore myocardial ischaemia-reperfusion injury increased ICAM-1 expression in the myocardium. 4. Administration of genistein (1 mg kg(-1), i.v., 5 min after coronary artery occlusion) lowered myocardial necrosis and MPO activity in the area-at-risk and in the necrotic area, decreased serum CPK activity, increased myocardial contractility, decreased the occurrence of ventricular arrhythmias, reduced serum and macrophages levels of TNF-alpha and blunted ICAM-1 expression in the injured myocardium. Finally genistein added in vitro to peritoneal macrophages collected from untreated rats subjected to myocardial ischaemia-reperfusion injury significantly reduced TNF-alpha production. 5. Our data suggest that genistein limits the inflammatory response and protects against myocardial ischaemia-reperfusion injury.

The rising incidence of breast cancer in women and prostate cancer in men. Dietary influences: a possible preventive role for nature's sex hormone modifiers - the phytoestrogens (review).

The rise in breast cancer in women and prostate cancer in men in Western societies this century, stimulated a search for any possibly reversible aetiological associations common to both. Apart from more citizens living to an older age the most significant associated factor in common is the dietary practices of communities most at risk, particularly a decreasing Western dependence on plant foods with increasing dietary animal fats. Plant foods, especially legumes like soy, contain phytoestrogens (plant oestrogens). They are natural hormone modifying agents and give balance to levels of circulating hormones in both sexes. Animal fats hinder hormone modulation. They retain and slowly release unwanted stored hormones. To reverse this situation Western communities could revert to Asian type diets with high soy content but a more practical approach might be to add concentrated soy or other phytoestrogen product to a fat reduced Western diet.