phytoestrogens and Body-Weight

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; 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Plant Oils; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Platelet Activation; Platelet Function Tests; Pneumonia, Viral; Poaceae; Pogostemon; Poloxamer; Poly I; Poly(ADP-ribose) Polymerase Inhibitors; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polycyclic Compounds; Polyethylene Glycols; Polylysine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Population Dynamics; Portasystemic Shunt, Transjugular Intrahepatic; Positron Emission Tomography Computed Tomography; Postoperative Complications; Postprandial Period; Potassium Cyanide; Predictive Value of Tests; Prefrontal Cortex; Pregnancy; Prepulse Inhibition; Prevalence; Procalcitonin; Prodrugs; Prognosis; Progression-Free Survival; Proline; Proof of Concept Study; Prospective Studies; Protein Binding; Protein Conformation; Protein Domains; Protein Folding; Protein Multimerization; Protein Sorting Signals; Protein Structure, Secondary; Proton Pump Inhibitors; Protozoan Proteins; Psychometrics; Pulse Wave Analysis; Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

In the assessment of the health risk of an obese individual, both the amount of adipose tissue and its distribution and metabolic activity are essential. In adults, the distribution of adipose tissue differs in a gender-dependent manner and is regulated by sex steroids, especially estrogens. Estrogens affect adipocyte differentiation but are also involved in the regulation of the lipid metabolism, insulin resistance, and inflammatory activity of the adipose tissue. Their deficiency results in unfavorable changes in body composition and increases the risk of metabolic complications, which can be partially reversed by hormone replacement therapy. Therefore, the idea of the supplementation of estrogen-like compounds to counteract obesity and related complications is compelling. Phytoestrogens are natural plant-derived dietary compounds that resemble human estrogens in their chemical structure and biological activity. Supplementation with phytoestrogens may confer a range of beneficial effects. However, results of studies on the influence of phytoestrogens on body composition and prevalence of obesity are inconsistent. In this review, we present data from in vitro, animal, and human studies regarding the role of phytoestrogens in adipose tissue development and function in the context of their potential application in the prevention of visceral obesity and related complications.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Diet; Humans; Obesity, Abdominal; Phytoestrogens

Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion.

Topics: 5-alpha Reductase Inhibitors; Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Dairy Products; Diet; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Male; Meat; Phytoestrogens; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Selective Estrogen Receptor Modulators; Selenium; Smoking Cessation; Vitamins

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; Enterobacteriaceae; Enterococcus faecalis; Enterotoxigenic Escherichia coli; Environmental Monitoring; Enzyme Inhibitors; Epidemiologic Factors; Epigenesis, Genetic; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Esterases; Esterification; Ethanol; Ethiopia; Ethnicity; Eucalyptus; Evidence-Based Practice; Exercise; Exercise Tolerance; Extracorporeal Membrane Oxygenation; Family; Fatty Acids; Feedback; Female; Ferric Compounds; Fibrin Fibrinogen Degradation Products; Filtration; Fish Diseases; Flavonoids; Flavonols; Fluorodeoxyglucose F18; Follow-Up Studies; Food Microbiology; Food Preservation; Forests; Fossils; Free Radical Scavengers; Freund's Adjuvant; Fruit; Fungi; Gallium; Gender Identity; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Genes, Bacterial; Genes, Plant; Genetic Predisposition to Disease; Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; Inflammation Mediators; Infrared Rays; Inhibitory Concentration 50; Injections, Intravenous; Interferon-gamma; Interleukin-23; Interleukin-4; Interleukin-6; Intermediate Filaments; Intermittent Claudication; Intestine, Small; Iridoid Glucosides; Iridoids; Iron; Isomerism; Isotope Labeling; Isoxazoles; Itraconazole; Kelch-Like ECH-Associated Protein 1; Ketoprofen; Kidney Failure, Chronic; Kinetics; Klebsiella pneumoniae; Lactams, Macrocyclic; Lactobacillus; Lactulose; Lakes; Lamivudine; Laparoscopy; Laparotomy; Laryngoscopy; Leucine; Limit of Detection; Linear Models; Lipid A; Lipopolysaccharides; Listeria monocytogenes; Liver; Liver Cirrhosis; Logistic Models; Longitudinal Studies; Losartan; Low Back Pain; Lung; Lupinus; Lupus Erythematosus, Systemic; Machine Learning; Macular Degeneration; Madin Darby Canine Kidney Cells; Magnetic Phenomena; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetics; Malaria, Falciparum; Male; Mannans; MAP Kinase Signaling System; Mass Spectrometry; Melatonin; Membrane Glycoproteins; Membrane Proteins; Meniscectomy; Menisci, Tibial; Mephenytoin; Mesenchymal Stem Cells; Metal Nanoparticles; Metal-Organic Frameworks; Methionine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Obese; Mice, Transgenic; Microbial Sensitivity Tests; Microcirculation; MicroRNAs; Microscopy, Video; Microtubules; Microvascular Density; Microwaves; Middle Aged; Minimally Invasive Surgical Procedures; Models, Animal; Models, Biological; Models, Molecular; Models, Theoretical; Molecular Docking Simulation; Molecular Structure; Molecular Weight; Morus; Mouth Floor; Multicenter Studies as Topic; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Muscle, Skeletal; Myocardial Ischemia; Myocardium; NAD; NADP; Nanocomposites; Nanoparticles; Naphthols; Nasal Lavage Fluid; Nasal Mucosa; Neisseria meningitidis; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms, Experimental; Neural Stem Cells; Neuroblastoma; Neurofilament Proteins; Neurogenesis; Neurons; New York; NF-E2-Related Factor 2; NF-kappa B; Nicotine; Nitriles; Nitrogen; Nitrogen Fixation; North America; Observer Variation; Occupational Exposure; Ochrobactrum; Oils, Volatile; Olea; Oligosaccharides; Omeprazole; Open Field Test; Optimism; Oregon; Oryzias; Osmolar Concentration; Osteoarthritis; Osteoblasts; Osteogenesis; Ovarian Neoplasms; Ovariectomy; Oxadiazoles; Oxidation-Reduction; Oxidative Stress; Oxygen; Ozone; p38 Mitogen-Activated Protein Kinases; Pakistan; Pandemics; Particle Size; Particulate Matter; Patient-Centered Care; Pelargonium; Peptides; Perception; Peripheral Arterial Disease; Peroxides; Pets; Pharmaceutical Preparations; Pharmacogenetics; Phenobarbital; Phenols; Phenotype; Phosphates; Phosphatidylethanolamines; Phosphines; Phospholipids; Phosphorus; Phosphorylation; Photoacoustic Techniques; Photochemotherapy; Photosensitizing Agents; Phylogeny; Phytoestrogens; Pilot Projects; Plant Components, Aerial; Plant Extracts; Plant Immunity; Plant Leaves; Plant Oils; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Platelet Activation; Platelet Function Tests; Pneumonia, Viral; Poaceae; Pogostemon; Poloxamer; Poly I; Poly(ADP-ribose) Polymerase Inhibitors; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polycyclic Compounds; Polyethylene Glycols; Polylysine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Population Dynamics; Portasystemic Shunt, Transjugular Intrahepatic; Positron Emission Tomography Computed Tomography; Postoperative Complications; Postprandial Period; Potassium Cyanide; Predictive Value of Tests; Prefrontal Cortex; Pregnancy; Prepulse Inhibition; Prevalence; Procalcitonin; Prodrugs; Prognosis; Progression-Free Survival; Proline; Proof of Concept Study; Prospective Studies; Protein Binding; Protein Conformation; Protein Domains; Protein Folding; Protein Multimerization; Protein Sorting Signals; Protein Structure, Secondary; Proton Pump Inhibitors; Protozoan Proteins; Psychometrics; Pulse Wave Analysis; Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

This paper reported the effects of commonly used whole soy foods (soy flour) and purified daidzein (one of the major isoflavones and the precursor of equol) on changes in anthropometric measurements and body composition in a 6-month double-blind, randomized, placebo-controlled trial among prehypertensive postmenopausal women who are also equol producers.. 270 eligible women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group), or 40 g low-fat milk powder (placebo group) daily each for 6 months. Anthropometric indicators and body composition were measured before and after intervention.. 253 subjects completed the study with good compliance. Urinary isoflavones levels suggested good compliance of subjects with supplementation. Whole soy and purified daidzein had no significant effect on body weight, body mass index (BMI), waist and hip circumferences, waist to hip ratio (WHR), body fat percentage, fat mass, and free fat mass.. Six-month consumption of whole soy and purified daidzein at provided dosage had no improvement on body weight and composition compared with isocaloric milk placebo among prehypertensive equol-producing postmenopausal women. This trial is registered with ClinicalTrials.gov NCT01270737.

Topics: Adiposity; Aged; Analysis of Variance; Body Composition; Body Mass Index; Body Weight; Double-Blind Method; Equol; Female; Hong Kong; Humans; Isoflavones; Middle Aged; Overweight; Phytoestrogens; Postmenopause; Predictive Value of Tests; Prehypertension; Soy Foods; Time Factors; Treatment Outcome; Waist Circumference; Waist-Hip Ratio

Postmenopausal women are particularly inclined to an increased risk of developing non-alcoholic hepatic steatosis. The purpose of this study was to investigate whether adding isoflavone supplementation to exercise training could reduce the risk.. In a 6-month, double-blind, randomized, controlled trial, 54 healthy overweight-to-obese (body mass index 28-40 kg/m2) postmenopausal women were randomly assigned to one of the following groups: (1) exercise and isoflavones (Ex-Iso; n = 26), (2) exercise and placebo (Ex-Pla; n = 28). Exercise training consisted of three weekly sessions of mixed training. We examined the plasma level of specific hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and alkaline phosphatase) as a reflection of fatty liver along with the calculation of the fatty liver index. All measures were obtained at baseline and after the 6-month intervention.. Following the intervention, a lower fatty liver index (p <0.01; 29% in Ex-Iso, 18% in Ex-Pla) and plasma γ-glutamyltransferase (p <0.01; 22% in Ex-Iso, 16% in Ex-Pla) were observed in both groups, with a higher reduction in the Ex-Iso group. On the other hand, for all other hepatic enzymes, there was no change.. Our results show that exercise training appears to bring favorable changes in the plasma level of hepatic enzymes, possibly due to the lowering of liver fat content. While postmenopausal women can benefit from this intervention to decrease the risk of developing non-alcoholic hepatic steatosis, it seems that the addition of isoflavones to exercise training provides some additional effects to those provided by exercise alone.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Analysis of Variance; Aspartate Aminotransferases; Body Composition; Body Mass Index; Body Weight; Energy Intake; Exercise; Fatty Liver; Female; gamma-Glutamyltransferase; Glycine max; Humans; Isoflavones; Middle Aged; Obesity; Phytoestrogens; Postmenopause; Statistics, Nonparametric; Waist Circumference

To evaluate the correlation between tear osmolarity and blood levels of 17-β estradiol, estrone, and testosterone in postmenopausal women with dry eye syndrome, and to assess the efficacy and safety of oral supplementation with phytoestrogens, lipoic acid, and eicosapentaenoic acid in this population.. Cross-sectional study including 66 postmenopausal women with dry eye syndrome.. Sixty-six postmenopausal women with dry eye syndrome were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients were divided into 2 groups (groups A and B) and treated, respectively, with phytoestrogen (Bioos, Montegiorgio, Italy) tablets or placebo tablets for 30 days. The 2 treatment periods were separated by a 30-day washout. Patients were examined on days 0 and 30 of each period. Assessments included blood levels of sex hormones, the Schirmer test for tear production, and measurement of tear osmolarity and tear film break-up time.. At baseline, all patients had low sex hormone levels, which were correlated with high tear film osmolarity values (r = -0.59,-0.61,-0.58, respectively). After 30 days of therapy, the group treated with Lacrisek® (Bioos) had significantly decreased tear osmolarity (P<0.005) and significantly increased tear production evaluated with the Schirmer test and tear film break-up time values (P<0.001) compared with the placebo-treated group.. Our study confirms that steroid hormones play an important role in ocular surface equilibrium and functions. Consequently, reduced blood levels of these hormones can produce changes at the ocular surface. Phytoestrogen supplementation can significantly improve the signs and symptoms of dry eye syndrome in postmenopausal women.

Topics: Body Weight; Chromatography, High Pressure Liquid; Cross-Over Studies; Cross-Sectional Studies; Dietary Supplements; Double-Blind Method; Dry Eye Syndromes; Estradiol; Estrone; Female; Humans; Middle Aged; Osmolar Concentration; Phytoestrogens; Postmenopause; Tablets; Tears; Testosterone; Treatment Outcome

We investigated the effects of consuming an isoflavone aglycone-enriched soya milk containing viable bifidobacteria on urinary isoflavone excretion and percentage recovery. Sixteen postmenopausal women were randomly divided into two groups to consume either fermented or non-fermented soya milk. Each group participated in a double-blind, crossover study with three 14 d supplementation periods, separated by a 14 d washout. Subjects ingested three daily dosages of isoflavone via the soya milk and collected four 24 h pooled urine specimens per supplementation period. Soya milks were prepared with soya protein isolate and soya germ, followed by fermentation with bifidobacteria. Isoflavone levels were quantified using HPLC. Non-fermented soya milks at 20, 40 and 80 mg isoflavone/200 ml contained 10 %, 9 % and 7 % aglycone, respectively, with their fermented counterparts containing 69 %, 57 % and 36 % aglycone (P<0.001). A trend to a greater percentage urinary recovery of daidzein and glycitein was observed among women consuming fermented soya milk at a dosage of 40 mg isoflavone (P=0.13). A distinct linear dose response for the fermented soya milk group (R2=0.9993) compared with the non-fermented group (R2=0.8865) suggested less interindividual variation in isoflavone absorption. However, total urinary isoflavone excretion was similar for both groups (P>0.05), with urinary isoflavone recovery at approximately 31 %. Increasing the isoflavone dosage correlated positively with its urinary excretion, but urinary percentage recovery of isoflavone was inversely related to dosage level. Hence, a modest dosage ranging from 20 to 30 mg/d may provide the most bioavailable source of isoflavone, regardless of whether it is via an aglycone-rich fermented soya milk or a glucoside-rich soya milk.

Topics: Bifidobacterium; Biological Availability; Body Mass Index; Body Weight; Cross-Over Studies; Double-Blind Method; Eating; Enzyme Inhibitors; Female; Fermentation; Genistein; Humans; Isoflavones; Middle Aged; Phytoestrogens; Postmenopause; Probiotics; Soy Milk

To assess the effect of phytoestrogens on bone turnover and growth in adolescent boys.. Randomized double-blind placebo-controlled trial.. Single school in northwest Tasmania.. Adolescent boys (treatment n=69, placebo n=59, mean age 16.8 y).. Six weeks of isoflavone supplementation (Novasoy, 50 mg daily of isoflavone equivalents). Bone turnover markers (bone specific alkaline phosphatase (BAP) and pyridinoline creatinine ratio (PYR)) were measured at baseline and follow-up.. Despite marked increases in urinary genistein and daidzein in the treatment arm (both P<0.001), there were no significant differences in BAP, PYR or short-term height or weight change. This applied to both intention-to-treat and per protocol analysis. Neither was there a significant correlation between urinary genistein and daidzein levels and BAP or PYR.. Phytoestrogen supplementation to the level of usual Japanese dietary intake has no measurable effect on bone turnover in adolescent boys. Longer-term studies of bone density may be desirable but it is unlikely that there will be a large effect in either girls or boys given the lower endogenous oestrogen levels in boys.

Topics: Adolescent; Body Height; Body Weight; Bone Density; Dietary Supplements; Estrogens, Non-Steroidal; Humans; Isoflavones; Male; Phytoestrogens; Plant Preparations; Tasmania; Time Factors

Steroid sex hormones play a central role in breast carcinogenesis. Evidence from in vitro and animal studies suggests that phytoestrogens may inhibit the development of mammary tumors through their role in regulating the synthesis, metabolism, and signal transduction of steroid hormones. In a study of 117 case-control pairs of postmenopausal women in Shanghai, we investigated whether the association between urinary phytoestrogen excretion and breast cancer risk may differ by levels of endogenous steroid sex hormones, sex hormone binding globulin (SHBG), body mass index (BMI), and waist:hip ratio (WHR). Fasting morning blood and urine samples were collected for the analysis of urinary isoflavonoids and mammalian lignans, as well as blood levels of SHBG and selected steroid hormones. For cancer patients, samples were collected before any cancer therapy. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals after adjusting for potential confounding factors. The inverse associations between urinary phytoestrogens and breast cancer risk were found to be more evident among women with a high BMI or WHR than those with a low level of these anthropometric measurements. Although a reduced risk of breast cancer was observed among women with a high excretion rate of urinary isoflavonoids in all of the strata defined by blood SHBG and steroid hormones, the inverse association was more pronounced among women with a high blood concentration of estradiol, a low level of estrone sulfate, or a low level of SHBG. The risks of breast cancer were also reduced with increasing excretion rate of mammalian lignans, although no test for a linear association was statistically significant in stratified analyses. Findings from this study suggest that the potential protective association of phytoestrogens may be modified by BMI, WHR, and blood levels of SHBG, and steroid hormones.

Topics: Adult; Age Factors; Anthropometry; Biomarkers, Tumor; Body Mass Index; Body Weight; Breast Neoplasms; Case-Control Studies; China; Dehydroepiandrosterone Sulfate; Eating; Estrogens; Female; Fibroadenoma; Humans; Isoflavones; Menopause; Middle Aged; Phytoestrogens; Plant Preparations; Risk Factors; Sex Hormone-Binding Globulin; Statistics as Topic; Testosterone; Women's Health

Phytoestrogen consumption has been shown to reduce risk factors for cardiovascular disease. Type 2 diabetes confers an adverse cardiovascular risk profile particularly in women after menopause. The aim of this study was to determine whether a dietary supplement with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes.. A total of 32 postmenopausal women with diet-controlled type 2 diabetes completed a randomized, double blind, cross-over trial of dietary supplementation with phytoestrogens (soy protein 30 g/day, isoflavones 132 mg/day) versus placebo (cellulose 30 g/day) for 12 weeks, separated by a 2-week washout period.. Compliance with the dietary supplementation was >90% for both treatment phases. When compared with the mean percentage change from baseline seen after 12 weeks of placebo, phytoestrogen supplementation demonstrated significantly lower mean values for fasting insulin (mean +/- SD 8.09 +/- 21.9%, P = 0.006), insulin resistance (6.47 +/- 27.7%, P = 0.003), HbA(1c) (0.64 +/- 3.19%, P = 0.048), total cholesterol (4.07 +/- 8.13%, P = 0.004), LDL cholesterol (7.09 +/- 12.7%, P = 0.001), cholesterol/HDL cholesterol ratio (3.89 +/- 11.7%, P = 0.015), and free thyroxine (2.50 +/- 8.47%, P = 0.004). No significant change occurred in HDL cholesterol, triglycerides, weight, blood pressure, creatinine, dehydroepiandrosterone sulfate, androstenedione, and the hypothalamic-pituitary-ovarian axis hormones.. These results show that dietary supplementation with soy phytoestrogens favorably alters insulin resistance, glycemic control, and serum lipoproteins in postmenopausal women with type 2 diabetes, thereby improving their cardiovascular risk profile.

Topics: Blood Glucose; Blood Pressure; Body Weight; Cardiovascular Diseases; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dietary Supplements; Double-Blind Method; Estrogens, Non-Steroidal; Female; Glycated Hemoglobin; Glycine max; Hormones; Humans; Isoflavones; Lipids; Patient Compliance; Patient Selection; Phytoestrogens; Phytotherapy; Placebos; Plant Preparations; Postmenopause

Isoflavonoids are a class of flavonoids that are derived in the human diet mainly from soybean-based foods. The major dietary isoflavonoids, genistein and daidzein, have estrogen-like activity and are classed as phytoestrogens. Because estrogens can lower serum LDL cholesterol and raise HDL cholesterol, the objective of this study was to determine if isoflavonoids could improve serum lipids in healthy subjects. Forty-six men and 13 postmenopausal women not receiving hormone replacement therapy completed a randomized, double-blind, placebo-controlled trial of two-way parallel design and 8 wk duration. One tablet containing 55 mg of isoflavonoids (predominantly in the form of genistein) or one placebo tablet was taken daily with the evening meal. Subjects maintained their usual diet and physical activity, which were unchanged throughout the intervention. Measurement of isoflavonoids and their metabolites in 24-h urine samples provided an assessment of compliance and of isoflavonoid metabolism. Serum total, LDL, HDL and HDL subclass cholesterol, triglycerides and lipoprotein (a) were assessed at baseline and during the last week of intervention. After adjustment for baseline values, no significant differences in postintervention serum lipid and lipoprotein (a) concentrations between groups were identified. Further adjustment for age, gender and weight change did not alter the results. In addition, changes in urinary isoflavonoids were not significantly correlated with changes in serum lipids and lipoprotein (a). Therefore, this study does not support the hypothesis that isoflavonoid phytoestrogens can improve the serum lipids, at least in subjects with average serum cholesterol concentrations.

Topics: Adult; Aged; Body Weight; Dietary Supplements; Double-Blind Method; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Lipids; Lipoproteins; Male; Middle Aged; Osmolar Concentration; Phytoestrogens; Plant Preparations

This study systematically investigated the effects of phytoestrogen glabrene on postmenopausal osteoporosis in an ovariectomy (OVX) rat model. Glabrene administration (25, 50, and 100 mg/kg) for 13 weeks can significantly slow down the body weight gain and slightly increase the uterus weight of OVX rats. The increased levels of U-Ca, U-P levels, urine DPD/creatinine, serum ALP, OCN, triglycerides, and total cholesterol induced by OVX were dramatically inhibited in rats, whereas no difference occurred for S-Ca and S-P in all groups. Furthermore, glabrene can enhance bone mineral density of the right femur, fourth-lumbar vertebra and tibia and improve biomechanical parameters, such as femoral neck loading force, three-point bending of the tibia, and vertebral compression in OVX rats. Moreover, glabrene greatly suppressed the expression of TRAP protein but increased OPG and BGP protein expression in tibia tissue of OVX rats. In addition, OVX-induced reduction of Lrp-5, β-catenin, Runx2, and Osx protein expression was all restored by glabrene treatment. The present study indicated that glabrene might be a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis via activation of the Wnt/β-catenin signaling pathway.

Topics: Animals; beta Catenin; Body Weight; Dose-Response Relationship, Drug; Female; Isoflavones; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Up-Regulation; Uterus; Wnt Signaling Pathway

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.

Topics: Adipocytes, White; Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Body Weight; Cell Enlargement; Cold-Shock Response; Diet, High-Fat; Eating; Energy Metabolism; Genistein; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Obesity; Phytoestrogens; Protective Agents

Coumestrol is a dietary phytoestrogen with estrogen-mimicking characteristics. This study investigated the molecular mechanisms of antiobesity effects of coumestrol. Two weeks of coumestrol treatment reduced body weight and improved glucose tolerance of high-fat diet (HFD)-fed mice. Notably, coumestrol treatment reduced adiposity but expanded brown adipose tissue mass. In addition, coumestrol treatment induced up-regulation of brown adipocyte markers and lipolytic gene expression in adipose tissue. Mechanistically, coumestrol induced an increase in mitochondrial contents of brown adipose tissue, which was associated with up-regulation of adenosine monophosphate-activated protein kinase and sirtuin 1. In vitro knockdown of estrogen receptor 1 inhibited the effect of coumestrol on brown adipogenic marker expression, increase in mitochondrial contents and oxygen consumption rate in brown adipocytes. Furthermore, lineage tracing of platelet-derived growth factor receptor A-positive (PDGFRA+) adipocyte progenitors confirmed increased levels of de novo brown adipogenesis from PDGFRA+ cells by coumestrol treatment. In conclusion, our results indicate that coumestrol has antiobesity effects through the expansion and activation of brown adipose tissue metabolism.

Topics: Adipocytes, Beige; Adipogenesis; Adipose Tissue, Brown; Adipose Tissue, White; Adiposity; Animals; Body Weight; Coumestrol; Diet, High-Fat; Glucose Tolerance Test; Lipolysis; Male; Mice; Mice, Inbred C57BL; Obesity; Phytoestrogens

Phytoestrogens are plant-derived compounds that can modulate estrogen activity in the brain and periphery. Laboratory rodent diets are typically high in soy-based phytoestrogens and therefore may influence neurophysiological and behavioural measures that are sensitive to estrogen signaling. Here we assessed such measures in rats (males and females) fed Australian made diets that varied in their soy levels. We found that a low-soy diet promoted greater weight, and lower levels of plasma estradiol, particularly in male rats. It also produced sex-specific effects on estrogen receptor gene expression in the brain, increasing ESR2 expression in the hippocampus and prefrontal cortex in female rats, and decreasing dopamine D1 receptor gene expression in the striatum of both male and female rats. We also found a dietary effect on short-term place recognition memory, but this was independent of soy levels in the diet. These results demonstrate that the choice of rodent laboratory diet can influence physiology, neurobiology and behavior, particularly on measures related to estrogen signaling.

Topics: Animals; Body Weight; Diet; Estrogens; Estrous Cycle; Female; Hippocampus; Male; Neostriatum; Phytoestrogens; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Sex Characteristics; Signal Transduction; Soy Foods; Spatial Memory

Daidzein application may represent an effective and less harmful alternative to indicated, classical estrogenization of ageing men. The aim of this study was to perform structural and hormonal analysis of the adrenal cortex, after estradiol or daidzein supplementation in a rat model of the andropause.. Middle-aged Wistar rats were divided into sham operated (SO; n = 8), orchidectomized (Orx; n = 8), estradiol treated orchidectomized (Orx + E; n = 8) and daidzein treated orchidectomized (Orx + D; n = 8) groups. Estradiol (0.625 mg/kg b.m./day) or daidzein (30 mg/kg b.m./day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. Set objectives were achieved using stereology, histochemistry/immunohistochemistry, immunoassays and ultrastructural analysis.. Both estradiol and daidzein treatment significantly increased volumes of the zona glomerulosa cell and nuclei, but decreased circulating aldosterone levels. Estradiol markedly increased volumes of the zona fasciculata cell and nuclei in parallel with significant decrease of the adrenal tissue level of corticosterone, while daidzein significantly decreased both the adrenal and circulating levels of corticosterone. Serum DHEA level and volumes of the zona reticularis cell and nuclei significantly increased upon estradiol treatment, whereas daidzein even stronger increased the circulating level of DHEA. Shunting of the corticosteroidogenesis pathways towards adrenal androgens production, after the treatments, corresponded to the ultrastructural findings and zonal capillary network rearrangements.. Given the coherence of its effects and relative safety, daidzein could be the remedy of choice for the treatment of ageing-caused androgen deprivation and the hypothalamo-pituitary-adrenal axis hyperfunction/related metabolic issues in males.

Topics: Adrenal Cortex; Aldosterone; Andropause; Animals; Body Weight; Corticosterone; Dehydroepiandrosterone; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Isoflavones; Male; Microscopy, Electron, Transmission; Mitochondria; Orchiectomy; Organ Size; Phytoestrogens; Potassium; Random Allocation; Rats; Rats, Wistar; Sodium

Estrogen is involved in lipid metabolism. Menopausal women with low estrogen secretion usually gain weight and develop steatosis associated with abnormal lipid metabolism. A previous study showed that blackcurrant (

Topics: Adipocytes; Adiponectin; Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Dyslipidemias; Fatty Liver; Female; gamma-Glutamyltransferase; Intra-Abdominal Fat; Leptin; Lipid Metabolism; Liver; Menopause; Non-alcoholic Fatty Liver Disease; Ovariectomy; Phytoestrogens; Plant Extracts; Rats; Rats, Sprague-Dawley; Ribes; Triglycerides

Phytoestrogens are nonsteroidal plant compounds with similar chemical structures to mammalian estrogen capable of mimicking the effect of estrogen in selective tissues. A diet rich in phytoestrogens is associated with a variety of health benefits including decreased risks for heart disease, breast cancer, and osteoporosis. Obesity has long thought to be associated with improved bone density due to increased mechanical loading, but recent literature suggests obesity may actually decrease bone health. Daidzein, a soy-derived phytoestrogen, has been shown to improve parameters of bone health in lean animal models of osteoporosis but has not been tested in obese animals. Following a one-week acclimation to a standard AIN-93G diet, 19 five-week-old female obese Zucker rats (OZR) were randomly assigned to a modified AIN-93G diet containing either high daidzein (HD, 0.121 g kg-1 feed) or low daidzein (LD, 0.01 g kg-1 feed). After 8 weeks, tibias and femurs were removed to assess true density (Archimedes principal), mechanical strength (three-point bending test), and femoral osteogenic gene expression. Serum was collected to assess osteocalcin and deoxypyridinoline. Our results indicated that there were no significant differences between the measures for tibial or femoral true density or mechanical strength for the rats in the HD and LD diet groups. Similarly, there were no significant differences in gene expressions related to osteogenic pathways, or serum biomarkers of bone formation and resorption. Overall, an increased dose of daidzein from soy protein supplementation does not elicit an improvement in markers of bone health in obese Zucker rats.

Topics: Amino Acids; Animals; Biomarkers; Body Weight; Bone and Bones; Bone Density; Diet; Dietary Supplements; Disease Models, Animal; Energy Intake; Female; Femur; Gene Expression; Isoflavones; Obesity; Osteocalcin; Osteogenesis; Osteoporosis; Phytoestrogens; Rats; Rats, Zucker

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diet, High-Fat; Enzyme Inhibitors; Fructose; Glycogen; Kidney; Lipase; Lipids; Liver; Male; Mice; Obesity; Phytoestrogens

Topics: Aging; Animals; Body Weight; Female; Glycine max; Hydroxycholesterols; Isoflavones; Lipid Metabolism; Liver; Organ Size; Phytoestrogens; Rats; Rats, Wistar; Thyroid Hormones

Genistein, a kind of phytoestrogen abundant in soybeans, is beneficial for alleviating non-alcoholic fatty liver disease (NAFLD), but the specific mechanism was not clearly understood. This study was designed to determine the effect of genistein on NAFLD and explore the possible mechanism. 36 male Sprague-Dawley rats were divided into 4 groups: the control group, high fat-high sucrose diet (HFS) group, HFS with 4mg/kg body weight genistein, and HFS with 8mg/kg body weight genistein. 12 weeks later, serum and hepatic lipid profiles, liver histopathological examination were characterized. The protein levels of liver AMP-activated protein kinase (AMPK), phosphorylation of AMPK (p-AMPK), acetyl-CoA carboxylase (ACC), phosphorylation of ACC (p-ACC) and sterol regulatory element binding protein 1 (SREBP-1) were determined by western blot. mRNA expressions of fatty acid synthase gene (FAS) and glycerol-3-phosphate acyltransferase (GPAT), peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transfer enzyme-1 (CPT-1) and acyl-CoA oxidase (ACO) were measured by reverse transcription polymerase chain reaction (RT-PCR). Results showed that genistein effectively improved serum and hepatic lipid metabolism and diminished fat accumulation in liver. And the protein level of hepatic p-AMPK and p-ACC were increased, but SREBP-1 was decreased by genistein. Meanwhile, the mRNA levels of FAS and GPAT were lower, but PPARα, CPT-1, ACO were higher in rats treated with genistein compared with HFS group. Collectively, genistein can improve hepatic steatosis via activating AMPK, thus promoting fatty acid oxidation and inhibiting lipid synthesis in liver.

Topics: AMP-Activated Protein Kinases; Animals; Body Weight; Diet, High-Fat; Fatty Liver; Genistein; Lipid Metabolism; Liver; Male; Non-alcoholic Fatty Liver Disease; Oxidation-Reduction; Phytoestrogens; PPAR alpha; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Sucrose

Genistein is a phytoestrogen found in soy and soy-based products. Previously, we found that genistein adversely affected estradiol levels and follicle growth in vitro. Proper hormone production and follicle growth are key regulators of normal fertility. Therefore, we hypothesized that genistein adversely affects female fertility and pregnancy outcomes. To test this hypothesis, we dosed sexually mature female CD-1 mice (35days) with 0, 300, 500, or 1000ppm genistein for 30, 60, 150, and 240days. At the end of the dosing periods, we measured mating rate, pregnancy rate, fertility rate, gestation time, parturition time, pup mortality, litter size, average pup weight, and estradiol and progesterone levels. We found that chronic, preconception exposure to genistein affects gestation time, parturition time, litter size, pup weight, and pup mortality. Additionally, genistein exposure for 240days appears to have a protective effect on fertility rate, but does not affect hormone levels in vivo.

Topics: Animals; Body Weight; Diet; Estradiol; Female; Fertility; Genistein; Litter Size; Liver; Male; Mice; Organ Size; Ovary; Phytoestrogens; Pregnancy; Progesterone; Reproduction; Uterus

Associations of bone mineral density (BMD) with specific food components, including dietary fiber and isoflavones (that have a negative association with serum estrogen), are unclear and need to be determined, particularly in populations more likely to consume large amounts of these nutrients (such as young athletes).. To determine dietary intake of specific food components in athletes with oligoamenorrhea (OA) compared to athletes with eumenorrhea (EA) and nonathletes (NA), and associations of the dietary intake of these nutrients with lumbar spine BMD.. This cross-sectional study evaluated 68 OA, 24 EA, and 26 NA individuals aged 14 to 23 years. Measurements included 4-day food records, a dual x-ray absorptiometry scan evaluating lumbar spine BMD and body composition, and hormone levels. Multivariate analysis was used to estimate associations of nutrients with lumbar spine BMD.. Compared with EA and NA, OA had higher intake of fiber, phytic acid, and vegetable protein (all P values <0.0001). Intake of isoflavones, genistein, and daidzein was higher in OA than NA (P=0.003 and P=0.0002, respectively). OA had lower consumption of energy from saturated fatty acids than NA (P=0.002). After controlling for confounders such as body weight, menstrual status (indicative of estrogen status), calcium intake, and serum vitamin D (known BMD determinants), lumbar spine BMD z scores were inversely associated with dietary fiber (β=-.30; P=0.01), vegetable protein (β= -.28; P=0.02), phytic acid (β=-.27; P=0.02), genistein (β=-.25; P=0.01), and daidzein (β=-.24; P=0.01), and positively associated with percent energy from fatty acids (β=.32; P=0.0006).. Compared with EA and NA, OA had a higher dietary intake of fiber, vegetable protein, and phytic acid, which were inversely associated with lumbar spine BMD z scores. Further studies are needed to assess dietary recommendations for OA to optimize bone accrual.

Topics: Adolescent; Athletes; Body Mass Index; Body Weight; Bone Density; Cross-Sectional Studies; Diet; Diet Records; Dietary Fats; Dietary Fiber; Estrogens; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Humans; Multivariate Analysis; Oligomenorrhea; Phytic Acid; Phytoestrogens; Plant Proteins, Dietary; Vitamin D; Young Adult

Due to their functional similarity to estradiol, phytoestrogens could prove to be beneficial in late gestating sows. The goal of this study was to determine the impact of providing the phytoestrogen genistein during late pregnancy on the performance of sows and their litters. In total, 56 gilts were equally divided into the two following groups on day 90 of gestation: (1) controls (CTL); and (2) two daily i.m. injections of 220 mg of genistein (GEN). Treatments were carried out until farrowing. Jugular blood samples were collected from 16 gilts/treatment on days 89 and 110 of gestation, and on days 3 and 21 of lactation. Milk samples were also obtained from those sows on day 3 of lactation. A male piglet from 16 CTL and 15 GEN litters was slaughtered at 24 h postpartum and a blood sample was obtained. The liver, heart and visceral organs were weighed and the semitendinosus (ST) muscle was collected and carcass composition was determined. The treatment increased (P0.1) on weight or backfat loss of sows during lactation, milk composition or weights of piglets. The pre-weaning mortality rate of piglets was very low (0.1). However, carcasses from GEN litters contained more fat than those from CTL litters (9.63% v. 8.34%, P0.1). In conclusion, injecting gilts with 440 mg/day of genistein in late gestation increased IGF1 concentrations in gilts and carcass fat in neonatal piglets, but had minimal effect on muscle development of piglets at birth and on the performance of lactating sows and their litters.

Topics: Animals; Body Weight; Female; Fetal Development; Genistein; Injections, Intramuscular; Male; Mammary Glands, Animal; Muscle, Skeletal; Organ Size; Phytoestrogens; Sus scrofa

Genistein, a natural food compound mainly present in soybeans, is considered a potent antioxidant and to improve glucose homeostasis. However, its mechanism of action remains poorly understood. Here, we analyzed whether genistein could antagonize the progression of the hyperinsulinemic normoglycemic state (pre-diabetes) toward full-blown T2DM in Zucker Diabetic Fatty (ZDF) rats by decreasing mitochondrial oxidative stress and improving skeletal muscle oxidative capacity. Rats were assigned to three groups: (1) lean control (CNTL), (2) fa/fa CNTL, and (3) fa/fa genistein (GEN). GEN animals were subjected to a 0.02% (w/w) genistein-enriched diet for 8 weeks, whereas CNTL rats received a standard diet. We show that genistein did not affect the overall response to a glucose challenge in ZDF rats. In fact, genistein may exacerbate glucose intolerance as fasting glucose levels were significantly higher in fa/fa GEN (17.6 ± 0.7 mM) compared with fa/fa CNTL animals (14.9 ± 1.4 mM). Oxidative stress, established by electron spin resonance (ESR) spectroscopy, carbonylated protein content and UCP3 levels, remained unchanged upon dietary genistein supplementation. Furthermore, respirometry measurements revealed no effects of genistein on mitochondrial function. In conclusion, dietary genistein supplementation did not improve glucose homeostasis, alleviate oxidative stress, or augment skeletal muscle metabolism in ZDF rats.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Diet; Genistein; Glucose; Glucose Tolerance Test; Homeostasis; Insulin Resistance; Mitochondria, Muscle; Muscle, Skeletal; Oxidation-Reduction; Oxidative Stress; Phytoestrogens; Rats, Zucker

Mesquite (Prosopis sp.) and Leucaena leucocephala are widespread legumes, widely used to feed several livestock species and as food source for human populations in several countries. Both mesquite and Leucaena contain several phytoestrogens which might have potential estrogenic effects. Thus, the aim of this study was to evaluate the effects of mesquite pod and Leucaena extracts on several aspects of behavior and reproductive physiology of the male rat. The effects of the extracts were compared with those of estradiol (E2) and of two isoflavones: daidzein (DAI) and genistein (GEN). The following treatments were given to groups of intact male rats: vehicle; mesquite pod extract; Leucaena extract; E2; DAI; GEN. The results indicate that mesquite pod and Leucaena extracts disrupt male sexual behavior in a similar way to DAI and GEN, but less than E2. The main disruptor of sexual behavior was E2, however after 40 and 50days of administration, both extracts and phytoestrogens disrupted sexual behavior in a similar way to E2. The extracts also increased testicular germ cell apoptosis, decreased sperm quality, testicular weight, and testosterone levels, as phytoestrogens did, although these effects were less than those caused by estradiol. The number of seminiferous tubules with TUNEL-positive germ cells increased in extracts treated groups in a similar way to phytoestrogens groups, and E2 caused the greatest effect. The number of TUNEL-positive cells per tubule increased only in Leucaena extract and E2 groups, but not in mesquite- and phytoestrogens-treated groups. Spermatocytes and round spermatids were the TUNEL-positive cells observed in all experimental groups. This effect was associated with smaller testicular weights without atrophy in experimental groups compared with control. Testicular atrophy was only observed in estradiol-treated males. Testosterone decreased in males of all experimental groups, compared with control, this androgen was undetectable in E2 treated males. These results suggest that mesquite pod and Leucaena extracts cause effects similar to those of phytoestrogens in male rat reproduction, these effects were lower than those caused by E2.

Topics: Analysis of Variance; Animals; Body Weight; Genistein; In Situ Nick-End Labeling; Isoflavones; Male; Mimosine; Phytoestrogens; Plant Extracts; Prosopis; Rats; Rats, Wistar; Reproduction; Sexual Behavior, Animal; Spermatozoa; Testis; Testosterone; Time Factors

Daidzein is an isoflavone derived from soybeans that exerts preventive effects on bone loss in ovariectomized (OVX) animals. These effects have been correlated with increasing serum equol levels. In the present study, we investigated the effects of antibiotic intake on equol metabolism from daidzein, and the corresponding levels of bone loss in OVX mice.. Eight-week-old female ddY mice (n = 42) were either ovariectomized (OVX) or subjected to a sham operation (sham). OVX mice were then divided into six dietary subgroups: control diet (control), 0.3 % kanamycin diet (KN), 0.1 % daidzein diet (Dz), 0.1 % daidzein and 0.0375 % kanamycin diet (Dz+KN3.75), 0.1 % daidzein and 0.075 % kanamycin diet (Dz+KN7.5), and 0.1 % daidzein and 0.3 % kanamycin diet (Dz+KN30). The mice were fed their respective diets for 4 weeks.. Uterine weight and femoral bone mineral density (BMD) were significantly lower in the OVX mice compared in the sham mice. No significant differences in uterine weight were observed among all OVX dietary subgroups. The Dz subgroup was found to exhibit higher plasma equol and O-desmethylangolensin (O-DMA) concentrations, as well as greater femoral BMD, compared to all other OVX subgroups. Furthermore, when compared to the Dz group, kanamycin intake decreased plasma equol and O-DMA concentrations, as well as femoral BMD in the OVX mice.. These results suggest that kanamycin intake inhibited the conversion of daidzein to equol and O-DMA, blocking the preventive effects of daidzein on bone loss in OVX mice. Therefore, the bone-protective effects of daidzein intake may be predominantly associated with increased plasma concentrations of either equol or O-DMA.

Topics: Administration, Oral; Animals; Biotransformation; Body Weight; Bone Density; Diet; Disease Models, Animal; Equol; Female; Femur; Humans; Isoflavones; Kanamycin; Mice; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Uterus

Oxidative stress is the major cause of neuronal cell degeneration observed in neurodegenerative diseases including vascular dementia (VaD), and hypertension has been found to increase the probability of VaD. Here, we investigated the effects of equol in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats (DHRs) and the associated VaD. The systolic blood pressure of rats treated with low- (10 mg per kg body weight) and high-dose (20 mg per kg body weight) equol for 4 weeks was lower than that of the control group by 12.18 and 17.48% in a dose-dependent manner, respectively (p < 0.05), which was regulated by inhibiting angiotensin-converting enzyme (ACE) activity and increasing the nitric oxide (NO) production. Equol-treated DHRs showed a significant decrease in both the swimming distance and time required to reach the escape platform (78.20 to 82.56%, p < 0.05). In addition, the probe trial session and working memory test indicated that equol improved the long- and short-term memory of the rats. Moreover, the brain antioxidant activity was increased by elevating the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, and the malondialdehyde (MDA) content and acetylcholinesterase (AChE) activity were decreased, indicating that equol suppressed oxidative stress. In conclusion, we demonstrated that equol exhibited comparable blood pressure (BP)-lowering and VaD-improving effects with the clinically used drug, lisinopril in DHRs while there was a positive correlation between the doses. Therefore, this bioactive compound may be useful for developing functional foods, thereby extending the application of equol-containing crops.

Topics: Acetylcholinesterase; Animals; Blood Pressure; Body Weight; Brain; Catalase; Dementia, Vascular; Desoxycorticosterone Acetate; Disease Models, Animal; Dose-Response Relationship, Drug; Equol; Glutathione Peroxidase; Hypertension; Malondialdehyde; Memory, Short-Term; Nitric Oxide; Oxidative Stress; Physical Conditioning, Animal; Phytoestrogens; Rats; Renin-Angiotensin System; Superoxide Dismutase; Swimming

The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake.

Topics: Animal Feed; Animals; Blood Glucose; Body Weight; Dietary Supplements; Eating; Gene Expression Regulation; Glucose Tolerance Test; Hypothalamus; Male; Obesity; Phytoestrogens; Rats; Rats, Wistar

Gouania longipetala is commonly used in Cameroonian traditional medicine to manage women fertility and menopausal complaints. However, despite this use, the estrogenic properties of G. longipetala have not been studied until now.. The present study was aimed to assess estrogenic activities of the stem bark aqueous (GLA) and ethanolic (GLE) extracts of G. longipetala in post-menopause-like model of ovariectomized (Ovx) Wistar rats.. Animals were either sham-operated or Ovx. 84 days after ovariectomy, animals were divided into seven groups of five animals and were daily treated for 28 days with distilled water (10 mL/kg) for group 1, 2% solution of Tween 80 (10 mL/kg) for group 2, estradiol valerate (1 mg/kg) for group 3, GLA (45 or 180 mg/kg) and GLE (40 or 160 mg/kg) for groups 4 to 7 respectively. Sham-operated animals daily received distilled water (10 mL/kg). During the experimental period, the body weight was registered every week. At the day 29, blood pressure was registered by invasive method while uterine and vagina morphometry as well as body, uterine and abdominal fat weights changes were analyzed. Serum levels of total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol were determined. Moreover, oxidative stress markers such as nitrites, reduced glutathione (GSH) and malondialdehyde (MDA) were measured in homogenized liver and aorta.. Compared with the sham control, vagina and uterine dystrophy and elevated blood pressure were observed in Ovx rats treated with vehicles. Biochemical parameters showed a significant increase of total cholesterol, triglycerides, LDL-cholesterol and MDA as well as a significant decrease of nitrites and GSH in Ovx animals treated with vehicle as compared to sham group. GLA and GLE displayed estrogen-like effects on vagina and did not affect uterine wet weight and epithelial height compared with vehicle groups. Both extracts displayed anti-atherogenic properties by reducing AI, AIP and LDL-cholesterol level as compared to vehicles groups. GLA and GLE significantly prevented the increase of MDA induced by ovariectomy as compared to rats treated with vehicles.. This study showed that GLA and GLE exhibited estrogenic effects by providing vaginal lubrication, by modulating blood pressure and improving lipid profile, oxidative status and endothelial function and may not have an undesirable influence on the endometrium in ovariectomized rats.

Topics: Adipose Tissue; Animals; Blood Pressure; Body Weight; Cholesterol; Epithelium; Female; Ovariectomy; Oxidative Stress; Phytochemicals; Phytoestrogens; Plant Bark; Plant Extracts; Postmenopause; Rats; Rats, Wistar; Rhamnaceae; Triglycerides; Uterus; Vagina

Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage.

Topics: Adipocytes; Animals; Antimetabolites, Antineoplastic; Body Weight; Bone and Bones; Bone Density; Bone Marrow; Bone Resorption; Gene Expression Regulation; Genistein; Male; Methotrexate; Phytoestrogens; Rats; Rats, Sprague-Dawley

Millettia macrophylla Benth is a Cameroonian medicinal plant traditionally used to alleviate menopause-related problems. The methanol soluble fraction of this plant was shown to exhibit estrogenic effects in vitro in Human Embryonic kidney cells, and in vivo on ovariectomized rat following the classical uterotrophic assay. Since estrogens have been involved in bone remodeling process, the present study then aimed at evaluating bone loss preventive effects of the methanol soluble fraction of Millettia macrophylla (MM-met) in ovariectomized rat model.. Twenty-five healthy Wistar female rats (3-month-old) were randomly assigned to a sham-operated group and to four treated ovariectomized (OVX) groups. Treatments lasted 8 weeks and animals were sacrificed. The uterus, the femoral and the tibia bones of each animal were collected, weighed and fixed in 10% formalin for histological analysis.. Results showed that ovariectomy decreased uterine wet weight (p<0.01), induced body weight gain (p<0.01), decreased both femoral and tibia bone density and mineral content and increased alkaline phosphatase activity (p<0.05). E2V and MM-met treatments in general prevented bone mass loss and/or bone density loss. At all tested doses, MM-met induced a significant decrease of alkaline phosphatase activity (p<0.05). As observed with E2V, MM-met also induced a significant protective effect on bone, and this was indicated by an abundance of bone marrow in an almost intact trabecular network.. The overall results show that the methanol soluble fraction of Millettia macrophylla may prevent ovariectomy-induced bone mass loss and deterioration of the trabecular microarchitecture.

Topics: Alkaline Phosphatase; Animals; Body Weight; Bone Density; Bone Density Conservation Agents; Bone Marrow; Disease Models, Animal; Female; Femur; Leg Bones; Millettia; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Rats, Wistar; Tibia

Icariin, Genistein, and Hispidulin have been proven to have estrogen-like and antiosteoporotic activity and can be potentially used for the treatment of osteoporosis. The present study found that Icariin, Genistein, and Hispidulin treatments, emulating estrogen, significantly contributed to bone density. Comparative effects of Icariin, Genistein, and Hispidulin with estrogen on in ovariectomized rats were investigated. Our results showed that genistein was found to have superior bone protective effects against osteoporosis among genistein, Icariin, and Hispidulin.

Topics: Animals; Biomarkers; Blood Chemical Analysis; Body Weight; Bone and Bones; Bone Density; Female; Flavones; Flavonoids; Genistein; Organ Size; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Urinalysis; Uterus

Genistein is a phytoestrogen, particularly abundant in soybeans, that is able to bind estrogen receptors exerting both estrogenic and antiestrogenic activities. Genistein is largely present in the human diet even during pregnancy. Embryos and fetuses are therefore, commonly exposed to genistein during the development and after birth. In the present study, we used a murine model as a test end-point to investigate the effects of early exposure to genistein on adult male behavior and related neural circuits. Daily exposure of dams to genistein (100 μg/g of body weight) during late pregnancy and early lactation, produced in male offspring, when adults, significant changes in anxiety and aggressive behaviors. Moreover, we found statistically significant variations in the number of neuronal nitric-oxide synthase positive cells in the amygdala. In conclusions, these data indicate that early exposure to phytoestrogens may induce life-long effects on the differentiation of brain structures and behaviors.

Topics: Age Factors; Aggression; Amygdala; Animals; Anxiety; Body Weight; Dose-Response Relationship, Drug; Exploratory Behavior; Female; Genistein; Lactation; Male; Maze Learning; Mice; Nitric Oxide Synthase; Paraventricular Hypothalamic Nucleus; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Sexual Behavior, Animal

The effect of phytoestrogen-rich diet administered to male rats in a dose 20 mg/kg of body weight for 30 days with the mixture of phytoestrogens on reproductive function of male offspring and the effect of additional phytoestrogenization during milk feeding have been investigated. It was shown that male phytoestrogenization leads to feminization of the offsprings. Specifically, at birth, the ano-genital distance in males was less than that measured in control rats: (2.7 +/- 0.1) vs (3.1 +/- 0.0) mm (P < 0.05). This and additional phytoestrogenization of newborn rats during milk feeding inhibit their somatic and sexual development, weakening sexual activity in adults and reducing fertility at the expense of dectreased fertilizing capacity of sperm. A possible mechanism for the observed effects may be a reduction of relative androgenization due to increased of estradiol concentration by 3-4 times. Analysis of the data revealed a significant impact of phytoestrogens in father's diet on reproductive function of their offsprings under conditions of additional phytoestrogenization after birth.

Topics: Animals; Animals, Suckling; Body Weight; Estradiol; Female; Fertility; Genetic Fitness; Lactation; Male; Paternal Exposure; Phytoestrogens; Rats; Sexual Behavior, Animal; Sexual Maturation; Sperm Count; Sperm Motility; Testosterone

This study aimed to investigate the possible protective effects of genistein (GEN), a phytoestrogen, on the liver injury induced in rats by thioacetamide (TTA; 200.0 mg·(kg body mass)(-1); administered 3 times a week by intraperitoneal injection). GEN (0.5, 1.0, or 2.0 mg·(kg body mass)(-1); by subcutaneous injection) was concurrently administered on a daily basis for 8 weeks, and its effects were evaluated 24 h after the administration of the last dose. The results from this study revealed that TTA-induced liver injury was associated with massive changes in the serum levels of liver biomarkers, oxidative stress markers, and liver inflammatory cytokines. Treatment of TAA-induced liver injury in rats with GEN decreased the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, and total and direct bilirubin, and increased the serum level of albumin. GEN also restored the liver levels of malondialdehyde and reduced glutathione, as well as tumor necrosis factor-alpha, interleukin-6, and their modulator nuclear factor kappa-light-chain-enhancer of activated B cells. From our results, it can be concluded that GEN attenuates the liver injury-induced in rats with TAA, and this hepatoprotective role is attributed to its anti-inflammatory and antioxidant properties.

Topics: Aneuploidy; Animals; Biomarkers; Body Weight; Chemical and Drug Induced Liver Injury; Cytokines; Genistein; Liver; NF-kappa B; Oxidative Stress; Phytoestrogens; Protective Agents; Rats, Wistar; Silymarin; Thioacetamide

Bisphenol A (BPA), a pervasive, endocrine disrupting compound (EDC), acts as a mixed agonist-antagonist with respect to estrogens and other steroid hormones. We hypothesized that sexually selected traits would be particularly sensitive to EDC. Consistent with this concept, developmental exposure of males from the polygynous deer mouse, Peromyscus maniculatus, to BPA resulted in compromised spatial navigational ability and exploratory behaviors, while there was little effect on females. Here, we have examined a related, monogamous species, the California mouse (Peromyscus californicus), where we predicted that males would be less sensitive to BPA in terms of navigational and exploratory behaviors, while displaying other traits related to interactions with females and territorial marking that might be vulnerable to disruption. As in the deer mouse experiments, females were fed either a phytoestrogen-free CTL diet through pregnancy and lactation or the same diet supplemented with BPA (50 mg/kg feed weight) or ethinyl estradiol (EE) (0.1 part per billion) to provide a "pure" estrogen control. After weaning, pups were maintained on CTL diet until they had reached sexual maturity, at which time behaviors were evaluated. In addition, territorial marking was assessed in BPA-exposed males housed alone and when a control male was visible in the testing arena. In contrast to deer mice, BPA and EE exposure had no effect on spatial navigational skills in either male or female California mice. While CTL females exhibited greater exploratory behavior than CTL males, BPA exposure abolished this sex difference. BPA-exposed males, however, engaged in less territorial marking when CTL males were present. These studies demonstrate that developmental BPA exposure can disrupt adult behaviors in a sex- and species-dependent manner and are consistent with the hypothesis that sexually selected traits are particularly vulnerable to endocrine disruption and should be a consideration in risk assessment studies.

Topics: Animals; Animals, Newborn; Benzhydryl Compounds; Body Weight; Estrogens; Estrogens, Non-Steroidal; Ethinyl Estradiol; Exploratory Behavior; Female; Lactation; Male; Mice; Models, Animal; Peromyscus; Phenols; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Sexual Behavior, Animal

Echinacoside (ECH), isolated from Cistanche tubulosa (Schrenk) R. Wight stems, has been reported to enhance bone regeneration in MC3T3-E1 cells in vitro. The objectives of this study were to investigate the antiosteoporotic effect of ECH on bone metabolism in the ovariectomized (OVX) rat model of osteoporosis in vivo.. Fifty-six aged 6 months female Sprague-Dawley rats were randomly assigned into sham-operated group (SHAM) and six OVX subgroups (n=8 each). The OVX rats were then subdivided into six groups treated with vehicle (OVX), Xian-ling-gu-bao (XLGB, 0.5 g/kg body weight/day, orally), 17β-estradiol (E2, 50 μg/kg body weight/day, orally) or ECH (30, 90, and 270 mg/kg body weight, daily, orally) for 12 weeks respectively. We evaluated the pharmacological effects of E2, XLGB and ECH against osteoporosis by evaluating the body weight, uterus wet weight, serum and urine biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture, bone histomorphology and uterus immunohistochemistry.. In OVX rats, the increases of body weight, serum hydroxyproline (HOP) levels, and the decreases of uterus wet weight and BMD were significantly reversed by ECH treatment. Moreover, three dosages of ECH completely corrected the increased urine concentration of calcium (Ca), inorganic phosphorus (P), and HOP observed in OVX rats. Furthermore, Micro-CT analysis results of distal femur showed that all ECH-treated groups notably enhanced bone quality compared to OVX group (p<0.05). Consistent with this finding, total femur BMD and biomechanical strength of tibia were significantly improved (p<0.05) after 12 weeks ECH administration. Histological results also showed the protective activity of ECH through promotion of bone formation and suppression of bone resorption. In addition, the ECH administration also significantly enhanced the expression of ER in the uteri according to immunohistochemical evaluation (p<0.05). Those findings, based on the serum and urine biochemical, BMD, Micro-CT, biomechanical test, histopathological and immunohistochemical parameters, showed that ECH has a notable antiosteoporotic effect, similar to estrogen, especially effective for prevention osteoporosis induced by estrogen deficiency.. These results suggest that ECH, as a new class of phytoestrogen, has a remarkable antiosteoporotic activity, and may be a promising candidate for treatment of postmenopausal osteoporosis induced by estrogen deficiency in a natural way through herbal resources.

Topics: Animals; Body Weight; Bone and Bones; Bone Density; Bone Density Conservation Agents; Calcium; Cistanche; Drugs, Chinese Herbal; Estradiol; Estrogens; Female; Glycosides; Hydroxyproline; Organ Size; Osteoporosis; Ovariectomy; Phosphorus; Phytoestrogens; Phytotherapy; Plant Extracts; Plant Stems; Random Allocation; Rats; Rats, Sprague-Dawley; Uterus

Androgen and estrogen play an important role in the pathogenesis of benign prostatic hyperplasia (BPH). Estrogen exerts its action through two distinct estrogen receptors (ERs) either ER-α or ER-β. The phytoestrogenic property of silymarin (SIL) has been previously characterized. Thus, this study examined the protective effect of SIL against testosterone-induced BPH in rats. In an initial dose-response study, SIL in a dose of 50mg/kg was the most effective in preventing the rise in prostate weight, prostate weight/body weight ratio and histopathologic changes induced by testosterone. Testosterone significantly decreased ER-β and increased ER-α and AR expressions as compared to the control group and these effects were significantly ameliorated by SIL. Furthermore, SIL significantly protected against testosterone-provoked decline in mRNA expression of P21(WAF1/Cip1) and Bax/Bcl-xl ratio as well as caspase-3 activity. SIL minimized the number of proliferating cell nuclear antigen (PCNA) positive cells as compared to testosterone-treated group. Moreover, SIL significantly blunted the inducible NF-κB expression and restored the oxidative status to within normal values in the prostatic tissues. Collectively these findings elucidate the effectiveness of SIL in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its phytoestrogenic, pro-apoptotic and anti-oxidative properties.

Topics: Animals; Antioxidants; Apoptosis; Body Weight; Caspase 3; Cell Proliferation; Dose-Response Relationship, Drug; Immunohistochemistry; Male; NF-kappa B; Organ Size; Oxidative Stress; Phytoestrogens; Proliferating Cell Nuclear Antigen; Prostate; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Receptors, Androgen; Receptors, Estrogen; RNA, Messenger; Silymarin; Testosterone

Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats.. Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i) a control group that received vehicle (distilled water and Tween 80); (ii) a group treated with 10 mg/kg body weight (BW) of Genistein (Gen 10); and (iii) a group treated with a higher dose of Genistein (Gen 100). The rats were treated daily for three weeks from postnatal day 22 (P22) to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study.. A reduction of the mean weekly BW gain and organ weights (uteri and ovaries) were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05). These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals.. Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

Topics: Animals; Body Weight; Estrogens; Female; Follicle Stimulating Hormone; Genistein; Luteinizing Hormone; Organ Size; Ovary; Phytoestrogens; Rats; Rats, Sprague-Dawley; Time Factors; Uterus

Stephania venosa Spreng is a traditional herb which has been used for cancer treatment as well as an aphrodisiac. The scientific literature strongly supports its in vitro antiproliferative effects on cancer cell lines and has suggested developing this plant as a potential anticancer drug. However, the in vivo steroidogenic activity and toxicity of this plant have never been tested. We analyzed the levels of five key isoflavones in the plant extract by quantitative HPLC and then evaluated the in vivo estrogenic activity and toxicity in ovariectomized rats, in comparison with the phytoestrogen-rich plant, Pueraria mirifica. Twenty rats were first ovariectomized, and then seven days later divided into four groups and gavaged daily with 0, 10 and 100 mg/kg body weight/day of S. venosa, or 100 mg/kg body weight/day of P. mirifica for 28 days. A trace amount of puerarin, daidzin and daidzein with a subtle amount of genistein and genistin were isolated from the S. venosa tuber extract. S. venosa tuber powder, at both doses, did not exhibit any detectable estrogenic activity in ovariectomized rats, as assessed by the vaginal cytology and uterotropic assays, whilst P. mirifica induced a remarkable vaginal and uterine proliferation. S. venosa induced a toxicological effect on the hematological values and histopathological appearance of metabolic organs. Taken together, these results suggest that S. venosa has no discernable estrogenic activity but that it is toxic, at least to ovariectomized rats. Thus, the use of this plant for anticancer treatment needs to be reassessed or used with caution.

Topics: Animals; Body Weight; Female; Ovariectomy; Phytoestrogens; Plant Extracts; Rats; Rats, Wistar; Stephania; Uterus; Vagina

While peripheral insulin resistance is common during obesity and aging in mice and people, the progression to type 2 diabetes (T2D) is largely due to loss of β-cell mass and function through apoptosis. We recently reported that genistein, a soy derived isoflavone, can improve glycemic control and β-cell function in insulin-deficient diabetic mice. However, whether it can prevent β-cell loss and diabetes in T2D mice is unknown. Our current study aimed to investigate the effect of dietary supplemented genistein in a nongenetic T2D mouse model. Nongenetic, middle-aged obese diabetic mice were generated by high fat diet and a low dose of streptozotocin injection. The effect of dietary supplementation of genistein on glycemic control and β-cell mass and function was determined. Dietary intake of genistein (250 mg·kg(-1) diet) improved hyperglycemia, glucose tolerance, and blood insulin level in obese diabetic mice, whereas it did not affect body weight gain, food intake, fat deposit, plasma lipid profile, and peripheral insulin sensitivity. Genistein increased the number of insulin-positive β-cell in islets, promoted islet β-cell survival, and preserved islet mass. In conclusion, dietary intake of genistein could prevent T2D via a direct protective action on β-cells without alteration of periphery insulin sensitivity.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dietary Supplements; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Genistein; Glucose Tolerance Test; Hyperglycemia; Insulin; Insulin-Secreting Cells; Lipids; Male; Mice; Mice, Inbred C57BL; Phytoestrogens

Current knowledge about dietary soy isoflavone-induced hormonal effects and potential priming effects for the responsiveness of the organism to other estrogens is insufficient. The present study examined the effects of pre- and postnatal soy isoflavone exposure on estrogen responsiveness by estrogen receptor agonists in the uteri of prepubertal Wistar rats. To this end, offspring were generated from dams already maintained on three dietary groups, (1) a phytoestrogen-free diet, (2) a soy isoflavone-rich diet with 232 ppm daidzein and 240 ppm genistein or (3) a custom-made diet supplemented with 700 ppm genistein (GEN). Then, F1 females continuously exposed to isoflavones from GD1 to PND21 and non-exposed controls were subjected to an immature uterotrophic assay to compare physiological parameters and the response to subcutaneous treatment with 17β-estradiol, GEN or an estrogen receptor subtype (ERα and ERβ)-specific agonist. Uterine wet weight (UWW), luminal epithelial height (LEH) and myometrial thickness (MMT) were determined. In addition, isoflavone plasma levels and mRNA expression profiles of relevant steroid receptors and of molecular markers for proliferation and estrogenicity were assessed for all groups. The influence of dietary isoflavones on the sensitivity to various estrogenic stimuli in these prepubertal animals was minor. Yet, the uterus of immature rats with high chronic GEN exposure alone showed already an increase in UWW, LEH and MMT. The myometrial response to GEN was more pronounced than that of the luminal epithelium, which may be due to a non-uniform distribution of steroid receptors, in particular the progesterone receptor. In conclusion, although the impact of a continuous, prenatally initiated exposure to dietary isoflavones on the uterine physiology of juvenile rats is modest, the possible priming effects of this exposure for beneficial or adverse late-onset consequences in adults should not be neglected.

Topics: Animals; Body Weight; Diet; Epithelium; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Regulation; Genistein; Isoflavones; Myometrium; Organ Size; Phytoestrogens; Pregnancy; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Receptors, Progesterone; RNA; RNA, Messenger; Sexual Maturation; Uterus

Globally, non-alcoholic fatty liver disease (NAFLD) continues to rise and isoflavones exert antisteatotic effects by the regulation of hepatic lipogenesis/insulin resistance or adiposity/a variety of adipocytokines are related to hepatic steatosis. However, there is very little information regarding the potential effects of daidzein, the secondary abundant isoflavone, on NAFLD. Here, we have assessed the hepatic global transcription profiles, adipocytokines and adiposity in mice with high fat-induced NAFLD and their alteration by daidzein supplementation.. C57BL/6J mice were fed with normal fat (16% fat of total energy), high fat (HF; 36% fat of total energy) and HF supplemented with daidzein (0.1, 0.5, 1 and 2 g per kg diet) for 12 weeks.. Daidzein supplementation (≥ 0.5 g per kg diet) reduced hepatic lipid concentrations and alleviated hepatic steatosis. The hepatic microarray showed that daidzein supplementation (1 g per kg diet) downregulated carbohydrate responsive element binding protein, a determinant of de novo lipogenesis, its upstream gene liver X receptor β and its target genes encoding for lipogenic enzymes, thereby preventing hepatic steatosis and insulin resistance. These results were confirmed by lower insulin and blood glucose levels as well as homeostasis model assessment insulin resistance scores. In addition, daidzein supplementation inhibited adiposity by the upregulation of genes involved in fatty acid β-oxidation and the antiadipogeneis, and moreover augmented antisteatohepatitic leptin and adiponectin mRNA levels, whereas it reduced the mRNA or concentration of steatotic tumor necrosis factor α and ghrelin.. These findings show that daidzein might alleviate NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines by the alteration of adipocyte metabolism.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Body Weight; Diet; Fatty Liver; Gene Expression Profiling; Insulin; Insulin Resistance; Isoflavones; Lipogenesis; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phytoestrogens; Reverse Transcriptase Polymerase Chain Reaction

Continuous, low-dose exposure to a phytoestrogen (1 mg/kg/day genistein) and/or to an antiandrogenic food contaminant (1 mg/kg/day vinclozolin) has been recently reported to affect male reproductive tract and fertility [1] in adults. We investigated whether alterations of the testis are already present at the end of in utero exposure using the same rat model and doses following exposure from conception to delivery. After vinclozolin exposure, we observed in the neonate a slight but significant alteration of steroidogenesis and gametogenesis with a reduction of testosterone secretion and of the number of gonocytes. In contrast, genistein exposure had no effect. While the vinclozolin-genistein mixture acts in a synergistic manner to induce the most significant alterations in the adult, interestingly, genistein antagonized the deleterious effect of vinclozolin on germ cells in the neonate. This difference emphasizes the importance of studying the effects of endocrine disruptors during various developmental stages to understand their effects.

Topics: Age Factors; Aging; Androgen Antagonists; Animals; Animals, Newborn; Body Weight; Diet; Drug Interactions; Endocrine Disruptors; Female; Genistein; Gestational Age; Male; Oxazoles; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Rats; Rats, Wistar; Sperm Count; Spermatozoa; Testis; Testosterone

Soy-derived isoflavones potentially protect against obesity and depression. In five different studies we examined the influence of soy-containing diets or equol injections on depression, serotonin levels, body weight gain (BW) and white adipose tissue (WAT) deposition in female Long-Evans rats at various stages of life [rats were intact, ovariectomized or experienced natural ovarian failure (NOF)].. In general, animals fed a soy-rich diet (Phyto-600) and/or administered equol (@ 5 mg/kg/day) displayed significant decreases in BW and WAT compared to a low-soy diet. When equol was injected alone (5 mg/kg/day), experiments 1, 4, and 5 demonstrated that body weight was significantly decreased. Equol has body weight control effects in females that are dependent on ovarian status and/or age of diet initiation. Experiments 1-4 all displayed no significant differences in depressive-related behavior as measured by the Prosolt forced swim test (PFST) when soy-rich (Phyto-600) or low-soy diets (Phyto-low) or equol treatments (5 mg/kg/day) were tested in female rats at various ages or hormonal status. Results of all the experiments are not presented here due to space limitations, but data from experiment 5 are presented. From conception female rats were exposed to either: a) a soy-rich (Phyto-600) or b) low-soy diet (Phyto-low). After 290 days all rats experienced NOF. At 330 days-old the animals were examined in the Porsolt forced swim test (PFST). One month later a second PFST was performed [after Phyto-low fed animals were injected with equol (5 mg/kg/day) for one week prior to the second PFST]. At the first PFST, serotonin and mobility levels were significantly decreased in the Phyto-low fed animals compared to animals that consumed the Phyto-600 diet. After equol injections at the second PFST, mobility and serotonin levels significantly increased in aged NOF rats fed the Phyto-low diet (to levels comparable to Phyto-600 fed animals).. Consumption of dietary isoflavones or equol exposure in rats has body weight controlling effects and equol specifically may have antidepressant potential dependent upon diet initiation and/or dosage of treatments. The current study demonstrates that equol is able to decrease body weight, abdominal WAT, and depressive-related behavior. While other factors and mechanisms may play a role, in part, the present results provide a greater understanding of how isoflavonoid molecules modulate the brain's influence on behavior.

Topics: Age Factors; Aging; Animals; Body Weight; Depression; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Equol; Female; Glycine max; Hormones; Isoflavones; Male; Obesity; Organ Size; Ovariectomy; Phytoestrogens; Rats; Serotonin; Soybean Proteins; Statistics, Nonparametric; Swimming

The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland.

Topics: Androgen Antagonists; Animals; Body Weight; Drug Combinations; Female; Food Contamination; Genistein; Hyperplasia; Lactation; Mammary Glands, Animal; Maternal Exposure; Oxazoles; Phytoestrogens; Rats; Rats, Wistar; Sexual Maturation; Vagina

This study was designed to investigate the potential estrogenic effects of perinatal dietary phytoestrogens on the rat uterus. Pregnant rats were divided to three groups provided the following diets: (1) rat chow, (2) rat chow with 7.5% Trifolium (T.) pratense, or (3) rat chow supplemented with 17β-estradiol (0.5 mg/kg). The dams in each group were kept on the same diet during pregnancy and lactation. Female offspring were euthanized on day 21 at which time body and organ weights were recorded and tissue samples were taken for histology. Immunohistochemistry was performed to detect estrogen receptor alpha (ERα) and progesterone receptor (PR) levels. Our results revealed estrogen-like biological effects of perinatal T. pratense exposure. Relative uterus and ovary weights in the experimental groups were increased compared to control. The number of uterine glands and luminal epithelium heights were also increased. However, there were no statistically significant changes detected in the immunostaining intensity of ERα and PR between the groups.

Topics: Animals; Animals, Suckling; Body Weight; Estrogen Receptor alpha; Female; Immunohistochemistry; Isoflavones; Lactation; Maternal Exposure; Organ Size; Phytoestrogens; Plant Components, Aerial; Pregnancy; Rats; Rats, Wistar; Receptors, Progesterone; Trifolium; Uterus

Development of urinary incontinence, for many women, occurs following menopause. Dietary phytoestrogens consumed over the long term may affect the contractile function and maintenance of the urinary bladder in post menopausal women. This study examined the muscarinic receptor mediated contractile responses in the rat isolated bladder in response to ovariectomy and long term dietary phytoestrogen consumption.. Ovariectomised or sham-operated female Wistar rats (8 weeks) were fed either normal rat chow (soy, phytoestrogens) or a non-soy (phytoestrogen free) diet. Bladders were dissected from rats at 12, 24 and 52 weeks of age and placed in 25 ml organ baths filled with McEwans solution.. The contractile response to carbachol, in 12 week old female rats did not change as a result of dietary phytoestrogens or ovariectomy (P>0.05). At 24 weeks of age, detrusor muscle strip responses to carbachol from non-soy fed ovariectomised rats were attenuated (P<0.05). At 52 weeks, bladder detrusor strip responses to carbachol were reduced in all treatment groups with the exception of the soy-fed sham operated rats.. These results suggest an age-related reduction in the contractile response of the detrusor to the muscarinic receptor agonist carbachol, which may be prevented by long term dietary phytoestrogen intake.

Topics: Age Factors; Animal Feed; Animals; Body Weight; Carbachol; Cholinergic Agonists; Female; Glycine max; In Vitro Techniques; Muscle Contraction; Muscle, Smooth; Organ Size; Ovariectomy; Phytoestrogens; Rats; Rats, Wistar; Receptors, Muscarinic; Soybean Proteins; Urinary Bladder; Urinary Bladder, Overactive

The effects of supplemental Se in rodent models may depend upon composition of the basal diet to which it is added. Wild-type male littermates of Transgenic Adenocarcinoma of Mouse Prostate mice were fed until 18 wk of age 1 of 2 Se-adequate stock diets high in soy (HS) or low in phytoestrogens (LP) or the same diets supplemented with 3.0 mg Se/kg diet as seleno-methylselenocysteine. Body and abdominal fat pad weights were lower (P < 0.01) in mice fed the HS diet. Supplemental Se reduced fat pad weights in mice receiving the LP diet but increased body and fat pad weights in mice consuming the HS formulation (P-interaction < 0.005). Serum free triiodothyronine concentrations were unaffected by supplemental Se in mice fed the LP diet but were decreased by Se supplementation of mice given the HS feed (P-interaction < 0.02). Free thyroxine concentrations were higher in mice consuming the HS diet regardless of Se intake (P < 0.001). Hepatic mRNA for iodothyronine deiodinase I was lower (P < 0.001) in mice fed the HS diet. Supplementation of Se increased this mRNA (P < 0.001) in both diet groups. Results from this study show a significant interaction between the composition of basal diets and the effects of supplemental Se with respect to body composition. These findings have important implications for future studies in rodent models of the effects of supplemental Se on heart disease, cancer, diabetes, and other conditions related to body weight and composition.

Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Diet; Dietary Supplements; Glycine max; Iodide Peroxidase; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phytoestrogens; RNA, Messenger; Selenium; Thyroxine; Triiodothyronine

This study is to explore the effects of quercetin (QUE) on the 3 week-old mice ovarian development and relative hormone levels. The 3 week-old mice were exposed to QUE (45, 25, and 5 mg x kg(-1) x hd(-1)) by gavage for 50 days. The estrous cycle during 50 days and the changes of hormone level such as FSH, LH, etc were monitored. Moreover, the ovaries were removed after sacrifice. The organ index was measured, and the ratios of different stages of follicles were analyzed by HE staining. Furthermore, the proportion of PCNA positive cells during all stages was detected by immunohistochemistry. The results showed that QUE could increase body weight of mice and reduce the anogenital distance (AGD) to some extent, and was able to disrupt mice's estrous cycle, but it could not extend or reduce the cycle regularity. It increased ovarian organ index with a dose-dependent manner. The proportion of the primordial follicle and secondary follicles rose obviously, and that of mature follicles', atretic follicles' and corpus luteums' reduced, while primordial follicle had no change. Immunohistochemistry analysis showed that QUE could effectively increase the percentage of proliferating cells in all kinds of follicles. Serum hormone assay showed that there were significant changes of FSH and LH levels. In summary, QUE showed an estrogen-like effect on mice's ovarian development. The weight of ovary, the proportion of all kinds of follicles, the development of ovarian cells and the level of plasma hormone in mice were altered obviously by oral administration of QUE.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Estrous Cycle; Female; Follicle Stimulating Hormone; Luteinizing Hormone; Mice; Ovarian Follicle; Ovary; Phytoestrogens; Proliferating Cell Nuclear Antigen; Quercetin; Random Allocation

The isoflavonoids found in soy have attracted great interest as dietary phytoestrogens that might be effective for postmenopausal hormone replacement therapy. Special attention has been devoted to the hormonal effects of various isoflavonoids, like genistein (GEN) and daidzein's (DAID) potent metabolite, equol (EQ). Here we aimed to investigate the short-term effects of genistein and equol on the proximal femur of ovariectomized (OVX) rats. Forty-eight, 3-month-old female Sprague-Dawley rats were ovarectomized; after eight weeks the bilateral osteotomy and osteosynthesis (OS) of their tibiae was performed and the rats were randomly divided into the following four groups: OVX control group (C), treated with estradiol-17beta (E2) -benzoate (E; daily intake 0.086 mg/d per animal), genistein (GEN; daily intake 12.7 mg/d per animal) and equol (EQ; daily intake 4.65 mg/d per animal). At 5 weeks postoperatively (OS), the breaking test was performed on the trochanteric region of femur. Additionally, histomorphometric assessment, and trabecular and cortical bone microstructure analyses were performed. The relative gain of body weight (BW) in the EQ (24 %) group was significantly (p < 0.05) lower than in the C (33 %) and GEN (30 %) groups. After treatment for 5 weeks, the maximal load (F(max)) and yield load (yL) were higher (p < 0.05 for the weight-adapted results) in the E (188.4 N resp. 113.1 N) and EQ (177.3 N resp. 112 N) groups as compared to C (162.8 N resp. 109.1 N) and GEN (165.7 N resp. 108.8 N). In the histomorphometric tests the E- (trabecular area (Tb.Ar) = 74.93 %, trabecular nodes/mm(2) (N.Nd/mm(2)) = 48.65) and EQ-treated (Tb.Ar = 63.13 %, N.Nd/mm(2) = 43.72) animals showed significant improvement with regard to Tb.Ar and trabecular connectivity (N.Nd./mm(2)) in comparison to C (Tb.Ar = 46.84, N.Nd/mm(2) = 31.86) and GEN (Tb.Ar = 48.22 %, N.Nd/mm(2) = 34.15). There were no differences in relative cortical width (Ct.Wi) among the four groups. The treatment with EQ resulted in improved biomechanical and histomorphometric properties as compared to the treatment with GEN. Thus, of the studied substances, EQ seems to be a possible alternative to hormone replacement therapy, but further studies are needed.

Topics: Animals; Biomechanical Phenomena; Body Weight; Bone and Bones; Bone Remodeling; Diet; Equol; Estradiol; Estrogens; Female; Femur; Genistein; Glycine max; Isoflavones; Ovariectomy; Phytoestrogens; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods.

Topics: Animals; Body Weight; Conditioning, Classical; Cues; Diet; Endocrine Disruptors; Fear; Female; Genistein; Growth and Development; Lactation; Learning; Male; Maternal Behavior; Maze Learning; Memory; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats; Rats, Sprague-Dawley; Space Perception

The role of soy in reducing breast cancer risk has been suggested to be associated with early exposure to isoflavones, which alter mammary gland morphology. The objective of the study was to determine the effect of dietary exposure to the enantiomers of a key soy isoflavone metabolite, equol, on mammary gland development and later chemoprotection using the DMBA-induced animal model of breast cancer. Animals were exposed to S-(-)equol or R-(+)equol (250 mg/kg diet) during the neonatal (0-21 days) or prepubertal (21-35 days) periods only. Histological evaluation of the mammary glands showed that both enantiomers fed neonatally via the dam led to significant precocial mammary gland differentiation. By day 50, early S-(-)equol or R-(+)equol exposure resulted in a decrease in immature terminal end structures and an increase in mature lobules, suggesting an early 'imprinting' effect. Despite these morphological changes to the mammary gland, neonatal and prepubertal exposure to equol had no long-term chemoprevention against mammary tumors induced by DMBA, although for R-(+)equol there was a trend to delaying tumor formation. In summary, early exposure to equol was not chemopreventive, but neither did it increase tumor formation in response to DMBA, suggesting exposure in early life does not influence breast cancer risk.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Animals, Newborn; Body Weight; Carcinogens; Disease Models, Animal; Equol; Female; Genistein; Isoflavones; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Organ Size; Phytoestrogens; Rats; Rats, Sprague-Dawley; Stereoisomerism; Time Factors

Cardiovascular disease is the leading cause of death among menopausal women in developed countries, mostly due to the loss of endogenous oestrogen protection. Soybean protein (SP) is rich in isoflavone phytoestrogens. This study aimed to determine the effect of SP on ovariectomised rats subjected to myocardial infarction and its possible cardio-protection.. The study was conducted on 30 adult female albino rats, which were divided into three groups: Group I comprised the sham-operated rats; Group II, the ovariectomised (OVX) rats fed a standard diet; and Group III, OVX rats fed a standard diet supplemented with SP (OVX plus SP). The rats were anaesthetised, and electrocardiograms were conducted. The rats were then sacrificed, after which their hearts and livers were removed, weighed and subjected to histopathological examination. Blood was collected to determine the lipid profile, and the levels of total triiodothyronine, tetraiodothyronine (T4), thyroid-stimulating hormone (TSH), creatinine phosphokinase (CPK), lactate dehydrogenase, superoxide dismutase (SOD) and malonedialdehyde (MDA).. The biochemical studies showed a significant increase in plasma CPK (Group II), MDA and triacylglycerol (Groups II and III) levels compared to Group I. The plasma SOD showed a significant decrease in Group II compared to Group I. Total cholesterol, low and very low density lipoprotein cholesterol levels showed a significant increase in Group II, and a significant decrease compared to Group I. Significant increases in T4 and TSH were found in Group III compared to Group II.. SP intake can be valuable in protecting the heart against an attack of acute myocardial infarction.

Topics: Animals; Body Weight; Cardiotonic Agents; Cardiovascular Diseases; Cholesterol, LDL; Cholesterol, VLDL; Electrocardiography; Female; Lipids; Myocardial Infarction; Ovariectomy; Phytoestrogens; Rats; Soybean Proteins; Triglycerides

To evaluate the effectiveness of phytoestrogens as alternatives for selective dysfunctional changes in the menopausal rabbit model.. Prospective, vehicle-controlled experimental study.. Reproductive pharmacology laboratory in a university department.. Twenty-four rabbits with experimentally induced menopause and six intact controls.. Surgical menopause was induced in 24 rabbits by ovariectomy. After 4 weeks of convalescence, three groups (n = 6) were given 100 microg/kg E(2) valerate, 100 microg/kg daidzein, or 6.68 mg/kg red clover extract daily for 12 weeks. The remaining six rabbits served as the operated control group.. Vaginal blood flow using Doppler flowmetry, before, during, and after pelvic nerve stimulation; and measured parameters of uterine weight, femoral bone density, clitoral cavernosal histology, and hormone levels.. After pelvic nerve stimulation, blood flow increased remarkably in the daidzein-treated group. Serum E(2) and uterine weight increased significantly in the estrogen group. Cavernosal structure was well preserved in all three treatment groups, and bone mineral density was lowest in ovariectomized controls (0.3467 g/cm(2)) and highest in the red clover (0.4012 g/cm(2)) groups.. Supplementing isoflavones for menopause leads to significant improvements in bone density, tissue integrity, and vaginal blood flow with minimal effect on uterine weight and may therefore be a viable alternative to conventional regimens using synthetic estrogens.

Topics: Animals; Body Weight; Female; Isoflavones; Laser-Doppler Flowmetry; Menopause; Models, Animal; Ovariectomy; Phytoestrogens; Plant Preparations; Rabbits; Sexual Dysfunction, Physiological; Trifolium; Vagina

Neonatal exposure to genistein (GEN), an isoflavone abundant in soy, favorably modulates bone mineral density (BMD) and bone strength in mice at adulthood. The study objective was to determine whether early exposure to a combination of the soy isoflavones daidzein (DAI) and GEN that naturally exists in soy protein-based infant formula results in greater benefits to bone at adulthood than either treatment alone. Male and female CD-1 mice (n = 8-16 pups per group per gender) were randomized to subcutaneous injections of DAI (2 mg x kg body weight(-1) x d(-1)), GEN (5 mg x kg body weight(-1) x d(-1)), DAI+GEN (7 mg x kg body weight(-1) x d(-1)), diethylstilbesterol (DES; positive control) (2 mg x kg body weight(-1) x d(-1)), or control (CON) from postnatal d 1-5 and were studied to 4 mo of age. BMD, biomechanical bone strength, and bone microarchitecture were assessed at the femur and lumbar vertebrae (LV). Females treated with DAI, GEN, DAI+GEN, or DES had greater (P < 0.05) BMD at the LV compared with CON and vertebra in the DAI and DES group were more resistant to compression fractures. Microstructural analyses demonstrated that treatment with DAI and GEN resulted in greater (P < 0.05) trabecular connectivity and trabecular thickness, respectively, than the CON. In conclusion, neonatal exposure to DAI and/or GEN had a positive effect on the skeleton of female mice at adulthood, but, compared with individual treatments, DAI+GEN did not have a greater benefit to bone in females or males.

Topics: Animals; Animals, Newborn; Body Weight; Bone Density; Bone Development; Drug Therapy, Combination; Female; Femur; Genistein; Isoflavones; Male; Mice; Phytoestrogens; Sex Characteristics; Spine

The effects of soy phytoestrogens on Morris water maze (MWM) performance and neuronal cholinergic enzyme activities and immunoreactivity were studied in ovariectomized (OVX) rats. The rats were assigned to four groups fed control diet (CD), 3.9 mg/kg 17beta-estradiol diet (E2), 263.4 mg/kg soy phytoestrogens diet (SP1), and 526.9 mg/kg soy phytoestrogens diet (SP2). In the MWM task, escape latency and path length were significantly less in the E2 and SP2 groups than in the CD group on the second day. Choline acetyltransferase (ChAT) activity in the cerebral cortex and ChAT immunoreactivity in the diagonal band of Broca were significantly greater in the E2, SP1, and SP2 groups than in the CD group. Acetylcholinesterase activity in the hippocampus in the E2, SP1, and SP2 groups was significantly lower than in the CD group. This study suggests that soy phytoestrogens affect the reference memory and neuronal cholinergic system in OVX rats.

Topics: Acetylcholinesterase; Animals; Body Weight; Brain; Choline O-Acetyltransferase; Estradiol; Female; Glycine max; Hypocotyl; Maze Learning; Memory; Ovariectomy; Phytoestrogens; Plant Extracts; Rats; Rats, Sprague-Dawley

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. The aim of the present study was to compare the effects of genistein, estradiol and raloxifene on the skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg) or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium content, macrometric parameters and mechanical properties were examined. Also the effects of genistein, estradiol and raloxifene (10(-9)-10(-7) M) on the formation of osteoclasts from neonatal mouse bone marrow cells and the activity of osteoblasts isolated from neonatal mouse calvariae were compared. In vivo, estrogen deficiency resulted in the impairment of bone mineralization and bone mechanical properties. Raloxifene but not estradiol or genistein improved bone mineralization. Estradiol fully normalized the bone mechanical properties, whereas genistein augmented the deleterious effect of estrogen-deficiency on bone strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This difference may explain the lack of genistein effect on bone mineralization observed in ovariectomized rats in the in vivo study. Concluding, our experiments demonstrated profound differences between the activities of genistein, estradiol and raloxifene towards the osseous tissue in experimental conditions.

Topics: Animals; Body Weight; Bone and Bones; Bone Density; Bone Marrow Cells; Bone Resorption; Calcification, Physiologic; Calcium; Cell Count; Cells, Cultured; Disease Models, Animal; Drug Combinations; Estradiol; Estriol; Female; Gene Expression; Genistein; Humans; Mice; Mice, Inbred BALB C; Organ Size; Osteoblasts; Osteoclasts; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Raloxifene Hydrochloride; Rats; Rats, Wistar; RNA, Messenger; Selective Estrogen Receptor Modulators; Thymus Gland; Uterus

Cardiac hypertrophy is a common finding in human patients with inborn errors of long-chain fatty acid oxidation. Mice with either very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD-/-) or long-chain acyl-coenzyme A dehydrogenase deficiency (LCAD-/-) develop cardiac hypertrophy. Cardiac hypertrophy, initially measured using heart/body weight ratios, was manifested most severely in LCAD-/- male mice. VLCAD-/- mice, as a group, showed a mild increase in normalized cardiac mass (8.8% hypertrophy compared with all wild-type (WT) mice). In contrast, LCAD-/- mice as a group showed more severe cardiac hypertrophy (32.2% increase compared with all WT mice). On the basis of a clear male predilection, we analyzed the role of dietary plant estrogenic compounds commonly found in mouse diets because of soy or alfalfa components providing natural phytoestrogens or isoflavones in cardioprotection of LCAD-/- mice. Male LCAD-/- mice fed an isoflavone-free test diet had more severe cardiac hypertrophy (58.1% hypertrophy compared with WT mice fed the same diet). There were no significant differences in the female groups fed any of the diets. Echocardiography measurement performed on male LCAD-deficient mice fed a standard diet at the age of approximately 3 months confirmed the substantial cardiac hypertrophy in these mice compared with WT controls. Left ventricular (LV) wall thickness of the interventricular septum and posterior wall was remarkably increased in LCAD-/- mice compared with that of WT controls. Accordingly, the calculated LV mass after normalization to body weight was increased by about 40% in the LCAD-/- mice compared with WT mice. In summary, we found that metabolic cardiomyopathy, expressed as hypertrophy, developed in mice because of either VLCAD deficiency or LCAD deficiency; however, LCAD deficiency was the most profound and seemed to be attenuated either by endogenous estrogen (in females) or by phytoestrogens present in the diet as isoflavones (in males).

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Animals; Body Weight; Cardiomegaly; Diet; Disease Models, Animal; Echocardiography; Female; Isoflavones; Male; Mice; Mice, Knockout; Myocardium; Organ Size; Phytoestrogens

Hatano high- and low-avoidance (HAA and LAA) rats are separated by breeding from Sprague-Dawley rats by high versus low rates of avoidance responses in a shuttle-box task. In addition, compared to HAA rats, LAA rats show lower running-wheel activity, later sexual maturation, 5-day estrous cycling, lower sperm motility, more pronounced immunological reactions, and are generally less reactive to stress. The present study was designed to compare the effects of transmaternal exposure to genistein on these characteristics between HAA and LAA rats. To this aim, litters from both strains were fostered onto Sprague-Dawley rats receiving genistein by gavage with 5 mg/animal/day from day 17 of pregnancy through day 21 of lactation. Inhibited growth after weaning and reduced uterine weight at weaning were observed in the LAA offspring reared by genistein-treated dams. IgM antibody production in response to sheep red blood cells was significantly decreased in the HAA offspring reared by genistein-treated dams. During restraint stress, the plasma concentration of corticosterone was significantly lower in the LAA offspring reared by genistein-treated dams. Strain-related differences were detected in shuttle-box avoidance performance, running-wheel activity, estrous cycling, and sperm motility. The results demonstrate that transmaternal exposure to genistein potentially affects the immunological and stress responses as well as the post-weaning growth of the offspring. It suggests that a comparative study using Hatano rats would be useful for studying the influence of endocrine active chemicals on the whole body systems.

Topics: Animal Husbandry; Animals; Animals, Newborn; Animals, Suckling; Antibody Formation; Avoidance Learning; Body Weight; Estrous Cycle; Female; Genistein; Growth and Development; Immobilization; Lactation; Male; Maternal Exposure; Organ Size; Phytoestrogens; Rats; Rats, Sprague-Dawley; Sexual Maturation; Sperm Motility; Stress, Physiological; Toxicity Tests; Uterus

To investigate the protective effect of 17beta-estradiol (E2), peganum harmala extract (PHE) administration and calorie restriction (CR) treatment (60%) on oxidative stress and hepato-toxicity in aged rats.. Eighteen months old animals that were treated at the age of 12 months were divided into 4 groups: normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group.. Aging significantly decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and increased lactate deshydrogenase (LDH), gamma-glytamyl transferase (GGT), phosphatase alkalines (PAL), aspartate and lactate transaminase (AST and ALT) activities in the liver. Aging also induced an increased lipid peroxidation level, histological changes and a decreased E2 level. However, treatment with E2, PHE, and CR increased 17beta-estradiol, and decreased hepatic dysfunction parameters and lipid peroxidation as well as histological changes in the liver of aged rats.. The antioxidant and hepatoprotective activity of PHE and CR is possibly attributed to its ability to increase E2 level, which as an antioxidant, acts as a scavenger of ROS. Further studies on the pharmaceutical functions of E2 in males may contribute to its clinical application.

Topics: Aging; Animals; Body Weight; Caloric Restriction; Catalase; Estradiol; Female; Glutathione Peroxidase; Liver; Male; Organ Size; Oxidative Stress; Peganum; Phytoestrogens; Plant Extracts; Rats; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

The high fructose-fed rat is widely used as a model of insulin resistance. Genistein, a soy isoflavone, has been shown to improve insulin sensitivity in this model. The present study investigated whether genistein could prevent fatty liver disease in this model.. Male Wistar rats were fed a diet containing starch (control) or 60% fructose (insulin-resistant model). Fifteen days later, rats in each dietary group were divided into two groups and were treated with either genistein (1 mg/kg per day) in dimethylsulfoxide (DMSO) or 30% DMSO alone. After 60 days, markers of liver injury, oxidative stress, interleukin (IL)-6, tumor necrosis factor (TNF)-α, lipids, lipoprotein profile, nitrite, and nitrosothiol in the plasma and liver were quantified. Liver sections were examined for 3-nitrotyrosine (3-NT) expression and pathological lesions.. Fructose-fed rats displayed hyperlipidemia, significant changes in plasma lipoprotein profile, and increases in IL-6 and TNF-α levels compared with control. In addition, the accumulation of lipids, liver injury, a decline in liver function, inactivation of the glyoxalase system, depletion of antioxidants, and increased 3-NT expression were observed in the fructose-fed group. Administration of genistein to fructose-fed rats significantly reduced these biochemical and histological abnormalities.. Genistein activates the antioxidant profile, decreases IL-6 and TNF-α concentrations, prevents oxidative damage, and ameliorates fatty liver in insulin-resistant rats.

Topics: Animals; Ascorbic Acid; Body Weight; Cholesterol; Fatty Liver; Genistein; Glutathione Peroxidase; Glutathione Reductase; Insulin; Insulin Resistance; Interleukin-6; Liver; Liver Function Tests; Male; Non-alcoholic Fatty Liver Disease; Organ Size; Phospholipids; Phytoestrogens; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha; Vitamin E

Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. Consumption of soy and genistein has been associated with a variety of beneficial effects in animals and humans, but concerns have also been raised regarding potential adverse effects of genistein, particularly with regard to reproductive toxicity and the induction or potentiation of carcinogenesis, due primarily to its weak estrogenic activity. Because of these concerns, genistein was selected as one of the compounds to be examined using a protocol designed to evaluate the effects of multigenerational and long-term exposures to doses of estrogenic agents that produce subtle reproductive tract lesions in developmentally exposed Sprague-Dawley rat pups. Results from the 2-year study are reported here, and results from the multigenerational reproductive toxicology feed study are reported separately (NTP, 2008a). Data from a preliminary dose range-finding feed study (NTP, 2007) that utilized exposure concentrations up to 1,250 ppm genistein were used to select dietary exposure concentrations of 0, 5, 100, and 500 ppm for the current study. The multigenerational reproductive toxicology study examined F(0) through F(4) generations with F(5) litters terminated at weaning and focused on reproductive endpoints (NTP, 2008a). Animals were exposed from the time that the F(0) generation was 6 weeks old through weaning of the F(3) generation, and animals of the F(0) through F(4) generations were necropsied at 20 weeks of age. The current study was a 2-year dietary study utilizing three exposure arms: continuous exposure from conception through 2 years (designated F(1) continuous, or F(1)C), exposure from conception through 20 weeks followed by control diet to 2 years [designated F(1) truncated at postnatal day (PND) 140, or F(1)T140], and exposure from conception through weaning followed by control diet to 2 years (designated F(3) truncated at PND 21, or F(3)T21). The "F(3)" designation for the F(3)T21 arm indicates that these animals were siblings of the F(3) animals from the multigenerational reproductive toxicology study (NTP, 2008a). The F(1)C and F(1)T140 animals were also siblings but were derived from a separate breeding that was identical to the procedure used to produce the F(1) generation of the mu. Under the conditions of this 2-year feed study with continuous exposure to the test compound from conception through termination (F(1)C), there was no evidence of carcinogenic activity of genistein in male Sprague-Dawley rats exposed to 5, 100, or 500 ppm. There was some evidence of carcinogenic activity of genistein in female Sprague-Dawley rats based on increased incidences of mammary gland adenoma or adenocarcinoma (combined) and pituitary gland neoplasms. The incidence of benign mammary gland fibroadenoma in female rats was significantly decreased in the 500 ppm group. Under the conditions of this 2-year feed study with exposure to the test compound from conception through 20 weeks followed by control feed until termination (F(1)T140), there was no evidence of carcinogenic activity of genistein in male Sprague-Dawley rats exposed to 5, 100, or 500 ppm. There was equivocal evidence of carcinogenic activity of genistein in female Sprague-Dawley rats based on marginally increased incidences of pituitary gland neoplasms. Under the conditions of this 2-year feed study where offspring of three prior generations of animals exposed to the test compound were exposed from conception through weaning (PND 21) followed by control feed until termination (F(3)T21), there was no evidence of carcinogenic activity of genistein in male Sprague-Dawley rats exposed to 5, 100, or 500 ppm. There was equivocal evidence of carcinogenic activity of genistein in female Sprague-Dawley rats based on increased incidences of mammary gland adenoma or adenocarcinoma (combined). Exposure to genistein was also shown to accelerate the onset of aberrant estrous cycles in female Sprague-Dawley rats whether exposures were continuous or truncated at PND 140 or at weaning. The effects of genistein on estrous cycling and the incidences of common hormonally related spontaneous neoplasms of female Sprague-Dawley rats are consistent with an estrogenic mechanism of toxicity.

Topics: Animals; Body Weight; Estrous Cycle; Female; Genistein; Kidney; Litter Size; Longevity; Male; Mammary Glands, Animal; Mammary Neoplasms, Animal; Neoplasms, Experimental; Phytoestrogens; Pituitary Neoplasms; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Reproduction; Toxicity Tests, Chronic; Xenobiotics

To find a more potent alternative with less oestrogen-related side effects for hormone replacement therapy (HRT) in postmenopausal osteoporosis, we designed and synthesized a NO-releasing prodrug of genistein (NO-G) according to the structure of NONSAIDs. The purpose of this study was to evaluate the effects of the prodrug on bone in ovariectomised (OVX) rats.. Forty-eight adult Sprague-Dawley female rats were ovariectomised and treated with vehicle, 9 mg/kg genistein and 4.5, 9 or 18 mg/kg NO-G by oral administration daily. The bioassays were performed in terms of bone mineral density (BMD), mechanical testing, bone formation markers, bone alkaline phosphatase (b-ALP) and osteocalcin (OCN) and bone resorption marker urine deoxypyridinoline (DPD). In addition, the effects of the drugs on uterus and body weight were examined.. After treatment for 12 weeks, the BMD of whole femur and tibia in the NO-G (9 and 18 mg/kg) groups were 12.1% and 12.2% higher than that of OVX group (P<0.01); the bending strength of the femur was 11.2% and 12.2% higher than OVX group (P<0.01). The OVX-induced increase of serum b-ALP, OCN and urinary DPD were markedly attenuated. The prodrug showed no side effects on uterus and body weight.. The NO-releasing prodrug of genistein improves the bone loss in OVX rats without stimulatory effects on the uterus, which suggests that the product could potentially be used for the prevention and treatment of postmenopausal osteoporosis.

Topics: Administration, Oral; Animals; Body Weight; Bone Density; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Genistein; Nitric Oxide; Osteoporosis; Ovariectomy; Phytoestrogens; Prodrugs; Rats; Rats, Sprague-Dawley; Treatment Outcome

Studies with oestrogen receptoralpha (ERalpha)- and ERbeta-selective compounds have already shown that the effects of 17beta-estradiol (E2) on body weight, movement drive and bone-protection are mediated via ERalpha. This study was based on the hypothesis that activation of ERbeta may antagonize ERalpha-mediated effects and designed to investigate potential effects of ERalpha/ERbeta heterodimers.. Ovariectomized (OVX) female Wistar rats were treated with combinations of the ERalpha-specific agonist 16alpha-LE2 (ALPHA; 1 and 10 microg kg(-1) d(-1)), the ERbeta-specific agonist 8beta-VE2 (BETA; 100 microg kg(-1) d(-1)), the phytoestrogen, genistein (10 mg kg(-1) d(-1)) and with the anti-oestrogen compound, ICI 182,780 (3 mg kg(-1) d(-1)) for three weeks. The combined effects of the substances on body weight increase, tibial bone mineral density (BMD) and the influence on running wheel activity (RWA) were investigated.. OVX-induced body weight increase was reduced by co-administration of genistein and BETA. Co-application of BETA or genistein with ALPHA had no effect on ALPHA-mediated bone-protection. The RWA of OVX animals was significantly reduced by treatment with genistein but stimulated by application of ALPHA. The stimulatory effect of ALPHA on RWA could be antagonized by co-treatment with the pure antioestrogen ICI 182,780 but also by co-administration of genistein or BETA.. Our results indicate that activation of ERbeta may modulate ERalpha-mediated physiological effects in vivo. The observation that substances with selective affinity for ERbeta are able to antagonize distinct physiological functions, like RWA, may be of great relevance to the pharmaceutical use of such drugs.

Topics: Animals; Body Weight; Bone Density; Dose-Response Relationship, Drug; Drug Therapy, Combination; Estradiol; Estrogen Antagonists; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Female; Fulvestrant; Genistein; Ligands; Motor Activity; Ovariectomy; Phytoestrogens; Rats; Rats, Wistar

After the heart and estrogen/progestin replacement study and the women's health initiative study, the prospect of hormone replacement therapy (HRT) on cardiovascular diseases (CVD) has changed dramatically. These findings led to various attempts to search for alternatives for classical HRT, e.g. phytoestrogens. The flavanone 8-prenylnaringenin (8-PN) was identified as a phytoestrogen with strong estrogen receptor-alpha activity. As the pituitary and the liver are targets for estrogen action, we assessed the effect of ovariectomy (OVX) and long-term treatment (3 months) with 17-beta estradiol benzoate (E(2)B) and 8-PN on pituitary and liver functions in adult OVX rats. Tested doses were 6.8 and 68.4 mg/kg body weight (BW) of 8-PN and 0.17 and 0.7 mg/kg BW of E(2)B. Our results demonstrate that 8-PN and E(2)B decreased BW and increased uterus weight. The high doses of E(2)B and 8-PN increased serum GH and decreased serum IGF-1 levels. E(2)B dose dependently decreased cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) concentrations in OVX rats. The high dose of 8-PN showed an estrogenic activity regarding cholesterol and LDL regulation but had no effect on HDL concentrations. By contrast, the low dose of 8-PN augmented HDL levels compared with intact rats. Triglyceride levels were raised in response to the high E(2)B dose but unaffected by 8-PN treatment. Taken together, 8-PN displays an anti-atherosclerotic profile that appears to be even more beneficial than the one displayed by E(2)B, and thus might demonstrate a remarkable potential for the prevention of CVD associated with estrogen deficiency.

Topics: Administration, Oral; Animals; Body Weight; Cholesterol; Chromatography, High Pressure Liquid; Estradiol; Estrogens; Female; Flavanones; Growth Hormone; Insulin-Like Growth Factor I; Lipid Metabolism; Lipoproteins, HDL; Lipoproteins, LDL; Organ Size; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Triglycerides; Uterus

Soy products are of particular interest because of their potential health benefits in a range of hormonal conditions, such as osteoporosis, due to their high content in phytoestrogens. Because equol, the main metabolite from soy isoflavones, is thought to be powerful, the present study was designated to evaluate the bone-sparing effects of equol by either providing the molecule through the diet or by eliciting its endogenous production by modulating intestinal microflora by short-chain fructooligosaccharides (sc-FOS) or live microbial (Lactobacillus casei) together with daidzein, its precursor.. A comparison with daidzein and genistein was also performed. Rats (3 months old) were ovariectomised (OVX) or sham-operated (SH). Ovariectomised rats were randomly assigned to six experimental diets for 3 months: a control diet (OVX), the control diet supplemented with either genistein (G), or daidzein (D), or equol (E) at the level of 10 microg/g body weight/d. The remaining OVX rats were given daidzein at the dose of 10 mug/g body weight/d, simultaneously with short-chain FOS (Actilight, Beghin-Meiji) (D+FOS) or Lactobacillus casei (Actimel, Danone) (D+L). The SH rats were given the same control diet as OVX.. Genistein, daidzein or equol exhibited a bone sparing effect. Indeed, total femoral bone mineral density (BMD) was significantly enhanced (compared to that of OVX rats), as was the metaphyseal compartment. Bone strength was improved by E consumption, but not by genistein or daidzein given alone. As far as the FOS diet is concerned, the addition of prebiotics significantly raised efficiency of the daidzein protective effect on both femoral BMD and mechanical properties. The effects of lactobacillus were similar, except that the increase in metaphyseal-BMD was not significant.. In conclusion, long-term equol consumption, like genistein and daidzein, in the ovariectomized rat, provides bone sparing effects. Adding indigestible sugars, such as FOS or live microbial as L. casei, in the diet significantly improves daidzein protective effects on the skeleton.

Topics: Animals; Biomarkers; Body Weight; Bone Density; Bone Resorption; Disease Models, Animal; Equol; Female; Femur; Genistein; Glycine max; Isoflavones; Organ Size; Osteocalcin; Osteoporosis; Ovariectomy; Phytoestrogens; Rats; Rats, Wistar; Uterus

Genistein is a phytoestrogen that occurs naturally in the diet and is found in a wide variety of plant-derived foods especially in soybeans and soy-based foods. There is wide spread interest in genistein and related phytoestrogens as chemopreventive agents for a variety of human diseases and cancers based on epidemiologic evidence of reduced cancer rates in populations with a high intake of soy. Soy, and hence its constituents, such as genistein, have been consumed at high levels in several Asian populations for many centuries without any apparent adverse effects and to the contrary, many health benefits have been associated with the ingestion of soy based foods. Concern has been raised, however, of potential adverse effects due to the estrogenic and other activities of the isoflavones and thus a comprehensive series of safety studies was performed with genistein. To assess the teratogenic and fetal toxic potential of genistein, several studies were conducted. Genistein was tested in an in vitro rat whole embryo culture assay (WEC), which is a preliminary screen, for fetotoxic and teratogenic potential, over a concentration range of from 1 to 100 microg/mL. Treatment related anomalies were observed at concentrations of >or= 10 microg and at 100 microg/mL, all embryos were malformed. Two in vivo embryo fetal developmental safety studies were conducted with genistein by oral administration (gavage and dietary admix) in which there was no evidence for a teratogenic effect. In an oral (gavage) embryonic and fetal development pilot study, genistein was administered to rats at dose levels of 0, 20, 150 and 1000 mg/kg/day from days 6-20 of gestation to females that were allowed to litter and rear their offspring up to day 7 of lactation. A slight maternal toxicity at 1000 mg/kg/day was observed as indicated by decreased body weight and food consumption and at this dose, adverse effects in the pups were observed including increased pup mortality, poor general condition, reduced pup body weights, and reduced pup milk uptake. At the high dose of 1000 mg/kg, no external malformations were noted, however some minor visceral and skeletal variations were observed. At the low dose of 20 mg/kg/day, an increased mortality, reduced milk uptake, a decreased % male sex ratio, and decreased body weights during lactation were observed. Due to lack of effects at the mid dose and the small number of animals, a relationship to treatment was considered unlikely. In an oral (dietar

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Animals, Newborn; Antineoplastic Agents; Body Weight; Eating; Embryo Culture Techniques; Female; Fetal Development; Genistein; Male; Musculoskeletal Abnormalities; No-Observed-Adverse-Effect Level; Organ Size; Phytoestrogens; Pilot Projects; Pregnancy; Random Allocation; Rats; Rats, Wistar; Reproduction; Sex Ratio

This study investigated the effects of soy isoflavone intake on uterotrophic responses in growing (juvenile) and adult female rats. In the growing rats, feed intake showed a decreasing trend as the level of dietary isoflavones increased to 0.02%, 0.1%, and 0.2% of the diets. However, in the case of the adult rats there were no significant differences among groups. Weight gains were significantly lower in the rats fed 0.1% and 0.2% isoflavones than the controls in both juvenile and adult rats. The urinary excretion of daidzein and genistein was significantly increased with increasing levels of dietary isoflavones. The calculated urinary recoveries of daidzein and genistein were significantly lower in the groups fed 0.1% and 0.2% isoflavones compared to the juvenile and adult rat groups fed 0.02% isoflavones; no significant difference was observed between the 0.1% and 0.2% groups. The calculated urinary recoveries of daidzein and genistein in the adult rats were significantly higher than in the juvenile rats. The differences in the urinary recoveries between ages may be due to greater availability of the isoflavones in the adult rats. Isoflavone supplementation did not alter the histological phenotype of endometrial cells in growing rats, but a hyperplastic response of endometrium was shown in the adult rats. Dietary isoflavones, therefore, may not have an estrogenic effect on the uterus at these dose levels during the growth period, but this organ would be expected to be a likely target for isoflavone action in adults. We observed in the present study that isoflavones are more bioavailable in adult rats than in the juvenile rats. Therefore, soy isoflavone supplementation may not act as an endocrine disrupter during the growth period but may exert a phytoestrogenic effect on the uterus of adult rats.

Topics: Aging; Animals; Biological Availability; Body Weight; Diet; Eating; Female; Genistein; Glycine max; Isoflavones; Phytoestrogens; Rats; Rats, Sprague-Dawley; Uterus

The optimum test diet and rodent species/strain for evaluating endocrine-disrupting compounds (EDCs) are critical.. We conducted studies to evaluate rodent species sensitivity and the effects of diets varying in phytoestrogen content on the time of vaginal opening (VO) in CD-1 mice, Fischer 344 (F344) rats, and CD Sprague-Dawley (S-D) rats.. Mice were weaned on postnatal day (PND) 15 and rats on PND19 and randomly assigned to control or test diets. Body weights, food consumption, and time of VO were recorded.. The time of VO was significantly advanced in F344 rats fed diets containing daidzein and genistein, whereas these same diets did not advance VO in S-D rats. When animals were fed the AIN-76A diet spiked with genistein, time of VO was significantly advanced at all doses in CD-1 mice, at the two highest doses in F344 rats, and at the highest dose in S-D rats. The time of VO in F344 rats was more highly correlated with the phytoestrogen content than with the total metabolizable energy (ME) of 12 diets.. The S-D rat is less sensitive to dietary phytoestrogens compared with the F344 rat or the CD-1 mouse, suggesting that the S-D rat is not the ideal model for evaluating estrogenic activity of EDCs. The profound effects of dietary phytoestrogens on the time of VO, an estrogen-sensitive marker, indicate that a standardized open-formula phytoestrogen-free diet containing a low ME level should be used to optimize the sensitivity of estrogenic bioassays.

Topics: Animals; Body Weight; Diet; Energy Metabolism; Feeding Behavior; Female; Genistein; Isoflavones; Mice; Phytoestrogens; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Vagina

Genistein is of great interest for its implications as an anticancer compound. We compared the effects of daily subcutaneous injections of 1mg/kg BW of genistein and vehicle (2% DMSO in peanut oil) for 20 weeks on N-nitroso-N-methylurea (NMU)-induced tumorigenesis in adult female rats. Genistein significantly increased tumor cross-sectional area and tumor multiplicity but not the tumor incidence and latency period when compared with the vehicle treated group. The serum E(2) levels of genistein treated group were significantly higher than those of the vehicle treated group at 1 and 2 months after treatment which is the time when most of the rats developed tumors. There were no significant differences in the length of the estrous cycle, food consumption and weights of body, livers, uteri and ovaries between the two groups. Our data shows that supplementation of genistein at a dosage comparable to the isoflavone consumption in humans did not affect the reproductive system but resulted in enhancement of NMU-induced tumorigenesis in adult female rats. Thus, the supplementation of soy isoflavone in premenopausal women may potentially potentiate the risk of breast cancer.

Topics: Animals; Antineoplastic Agents; Body Weight; Carcinogens; Cell Transformation, Neoplastic; Estradiol; Estrous Cycle; Female; Genistein; Mammary Neoplasms, Animal; Methylnitrosourea; Organ Size; Phytoestrogens; Rats; Rats, Sprague-Dawley

The present study was designed to investigate the effects of a phytoestrogens-containing soy extract (SOYSELECT, SSE) on the growth of estrogen-dependent (MCF-7) and estrogen-unresponsive (MDA-MB-231) human breast cancer xenografts in athymic mice. Results obtained provided evidence that MCF-7 tumors did not grow over the treatment period (5 weeks) in ovariectomized females receiving 50 or 100 mg/kg/day SSE (oral route); administration of SSE also did not affect the estradiol-sustained growth of MCF-7 tumors in mice. Similarly, no effects on tumor growth were observed in SSE-treated mice bearing MDA-MB-231 xenografts. Data from pS2, progesterone receptor and cyclin D1 mRNA expression in tumors showed that, although SSE was able to induce a moderate estrogenic effect in MCF-7 cells, it did not increase cellular proliferation and tumor growth, in our experimental conditions. Besides, when used in association with 17beta-estradiol, it displayed antiestrogenic activity. The expression of other genes involved in tumor progression and angiogenesis, such as Thrombospondin 1, Transforming Growth Factor beta2 and Kallikrein 6 was also evaluated in tumor samples, results showing a decrease in mRNA expression upon SSE treatment. The effect of SSE on angiogenesis in vivo was also evaluated in the Matrigel plug assay; results obtained showed a striking anti-angiogenic activity in mice receiving 100 mg/kg/day SSE, thereby confirming that this extract may interfere with angiogenesis. Collectively, these experimental data suggest that SSE could be not harmful for women with a history of or at high risk for breast cancer, at least for short treatment periods; however, further studies are needed to thoroughly characterize the activity profile of the extract in this specific setting of patients.

Topics: Animals; Body Weight; Cell Line, Tumor; Cell Proliferation; Female; Gene Expression; Humans; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic; Ovariectomy; Phytoestrogens; Plant Extracts; Reverse Transcriptase Polymerase Chain Reaction; Soybean Proteins; Uterus

As phytoestrogens are postulated as being neuroprotectants, we assessed the hypothesis that dietary isoflavone-type phytoestrogens are neuroprotective against ischemic stroke. Transient focal cerebral ischemia (90 min) was induced by middle cerebral artery occlusion (MCAO) following the intraluminal thread technique, both in rats fed with soy-based diet and in rats fed with isoflavone-free diet. Cerebro-cortical laser-Doppler flow (cortical perfusion, CP), arterial blood pressure, core temperature, PaO2, PaCO2, pH and glycemia were measured before, during and after MCAO. Neurological examination and infarct volume measurements were carried out 3 days after the ischemic insult. Dietary isoflavones (both glycosides and aglycones) were measured by high-performance liquid chromatography. Neither pre-ischemic, intra-ischemic nor post-ischemic CP values were significantly different between the soy-based diet and the isoflavone-free diet groups. Animals fed with the soy-based diet showed an infarct volume of 122 +/- 20.2 mm3 (19 +/- 3.3% of the whole ipsilateral hemisphere volume). In animals fed with the isoflavone-free diet the mean infarct volume was significantly higher, 191 +/- 26.7 mm3 (28 +/- 4.1%, P < 0.05). Neurological examination revealed significantly higher impairment in the isoflavone-free diet group compared with the soy-based diet group (3.3 +/- 0.5 vs. 1.9 +/- 0.5, P < 0.05). These results demonstrate that dietary isoflavones improve stroke outcome after transient focal cerebral ischemia in such a way that a higher dietary isoflavone content results in a lower infarct volume and a better neurological status.

Topics: Animals; Body Weight; Cerebral Infarction; Chromatography, High Pressure Liquid; Diet; Disease Models, Animal; Ischemic Attack, Transient; Laser-Doppler Flowmetry; Male; Neurologic Examination; Neuroprotective Agents; Phytoestrogens; Rats; Rats, Wistar; Reperfusion; Stroke; Time Factors

This study examines whether anti-diabetic effects of genistein and daidzein are mediated by hepatic glucose and lipid regulating enzyme activities in type 2 diabetic animals. Male C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice and age-matched non-diabetic littermates (db/+) were used in this study. The db/db mice were divided into control, genistein (0.02%, w/w) and daidzein (0.02%, w/w) groups. The blood glucose and HbA(1c) levels were significantly lower in the genistein and daidzein groups than in the control group, while glucose tolerance only was significantly improved in the genistein-supplemented group. The plasma insulin and C-peptide levels did not differ significantly between groups, yet the glucagon level was lower in the genistein and daidzein groups compared to that in the control db/db or db/+ group. The genistein and daidzein supplements increased the insulin/glucagon ratio in the type 2 diabetic animals. While the hepatic glucokinase activity was significantly lower in the db/db control group, the glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly higher in the control group compared to the db/+ group. Interestingly, these hepatic glucose metabolizing enzyme activities were reversed by the genistein and daidzein supplementation in db/db mice compared to the control group. The hepatic fatty acid synthase, beta-oxidation and carnitine palmitoyltransferase activities were all significantly lower in the genistein and daidzein groups than in the control group. The genistein and daidzein supplements also improved the plasma total cholesterol, triglyceride, HDL-cholesterol/total cholesterol, free fatty acid and hepatic triglyceride concentrations in the db/db mice. These results suggest that genistein and daidzein exert anti-diabetic effect in type 2 diabetic conditions by enhancing the glucose and lipid metabolism.

Topics: Animals; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Diet; Eating; Genistein; Glucagon; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Insulin; Isoflavones; Leptin; Lipid Metabolism; Liver; Liver Glycogen; Mice; Mice, Inbred C57BL; Phytoestrogens; Receptors, Cell Surface; Receptors, Leptin

Resveratrol (RES) is a phytoestrogen that has the ability to bind to estrogen receptors (ERs) and evoke biological effects that parallel those exerted by endogenous and synthetic estrogens. We have shown in previous studies that adult female rats acutely exposed to RES exhibit estrous cycle irregularity, ovarian hypertrophy, and alterations in sociosexual behavior. The present experiment characterizes the prolonged effects of maternal RES exposure throughout the lactational period on subsequent behavior, reproductive tissues, and brain morphology of the adult offspring. During adulthood, female offspring exposed to RES throughout nursing exhibited reduced body weight and increased ovarian weight, but exhibited normal estrous cyclicity and sociosexual behavior, without changes in the volume of the sexually dimorphic nucleus of the preoptic area or the anteroventral periventricular nucleus of the hypothalamus. During adulthood, males exposed to RES throughout nursing exhibited decreased body weight and plasma testosterone concentration, increased testicular weight, and reduced sociosexual behavior. These males also had significantly smaller sexually dimorphic nucleus of the preoptic area volumes and larger anteroventral periventricular nucleus volumes compared to male controls. These data suggest that postnatal exposure to RES may affect estrogenic activity in specific peripheral tissues (e.g., the gonads), while inducing antiestrogenic effects in the brain. Thus, the present study supports recent in vitro and in vivo findings that RES differs from most other phytoestrogens by acting as a possible mixed ER agonist/antagonist, depending on the tissue-specific availability of ER subtypes that are preferentially localized in specific brain regions and throughout the reproductive tract. More importantly these data indicate that maternal consumption of phytoestrogens during lactation can have lasting effects on the offspring that may not become apparent until they reach adulthood.

Topics: Animals; Animals, Newborn; Body Weight; Brain; Female; Male; Ovary; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Reproduction; Resveratrol; Seminal Vesicles; Sexual Behavior, Animal; Stilbenes; Testis; Uterus

Reduced estrogen levels occurring during menopause in woman are accompanied by a variety of disorders, e. g., hot flushes, depressions, osteoporosis, increase of body weight, and reduced movement drive. In this study we investigated the combined effects of physical activity, estradiol substitution, and a phytoestrogen-rich diet on bone mineral density, increase of body weight, and movement drive in an animal model. Ovariectomized (OVX) female Wistar rats were either fed an isoflavone-rich diet (IRD) or substituted with 17beta-estradiol (E2) for 3 months. Sham-operated rats (Sham) and vehicle-treated OVX animals served as controls. One half of the animals had the opportunity of voluntary wheel running. OVX rats displayed an eight times lower movement activity than Sham animals. E2 treatment, but not IRD, significantly increased the movement activity of OVX rats. During 3 months the lowest increase of body weight was observed in Sham animals, the highest rate in OVX animals. Along with running activity E2 treatment, but not IRD, also lowered the increase of body weight significantly compared to OVX animals. Bone mineral density (BMD) in the trabecular area of the tibia was strongly reduced in OVX rats compared to Sham animals. In contrast to IRD, E2 substitution resulted in a protection of BMD in this area compared to OVX animals. Our data demonstrate that body weight, movement drive, and BMD are positively influenced by E2. The steroid estrogen acts in the trabecular area of the tibia in a bone-protective manner, increases movement drive and antagonizes the increase of body weight. All these effects could not be observed in animals fed an isoflavone-rich diet.

Topics: Animals; Body Weight; Bone Density; Dietary Supplements; Disease Models, Animal; Estradiol; Female; Isoflavones; Motor Activity; Osteoporosis; Ovariectomy; Phytoestrogens; Phytotherapy; Rats; Rats, Wistar

Developmental effects of genistein (Gen) on the mammary gland were investigated using outbred female CD-1 mice treated neonatally on d 1-5 by sc injections at doses of 0.5, 5, or 50 mg/kg.d. Examination of mammary gland whole mounts (no. 4) before puberty (4 wk) revealed no morphological differences in development after Gen treatment. However, mice treated with Gen-50 had stunted development characterized by less branching at 5 wk and decreased numbers of terminal end buds at 5 and 6 wk. Conversely, at 6 wk, Gen-0.5-treated mice exhibited advanced development with increased ductal elongation compared with controls. Measurements of hormone receptor levels showed increased levels of progesterone receptor protein and estrogen receptor-beta mRNA in Gen-0.5-treated mice compared with controls; ERalpha expression was decreased after all doses of Gen treatment. Lactation ability, measured by pup weight gain and survival, was not affected after neonatal Gen-0.5 and Gen-5. Mice treated with Gen-50 did not deliver live pups; therefore, lactation ability could not be determined. Evaluation of mammary glands in aged mice (9 months) showed no differences between Gen-0.5-treated mice and controls but mice treated with Gen-5 and Gen-50 exhibited altered morphology including reduced lobular alveolar development, dilated ducts, and focal areas of "beaded" ducts lined with hyperplastic ductal epithelium. In summary, neonatal Gen exposure altered mammary gland growth and development as well as hormone receptor levels at all doses examined; higher doses of Gen led to permanent long-lasting morphological changes.

Topics: Animals; Animals, Newborn; Body Weight; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Genistein; Hormones; Immunohistochemistry; Lactation; Mammary Glands, Animal; Mice; Phytoestrogens; Pregnancy; Receptors, Prolactin; Reverse Transcriptase Polymerase Chain Reaction; Survival

There is a great deal of controversy surrounding the issue of hormone replacement therapy after transplantation. The question whether or not this therapy has effects in cardiac allograft vasculopathy (CAV), the Achilles heel of cardiac transplantation or other unique aspects of allograft function is still unknown.. We investigated the long-term effect of 17beta-estradiol as well as phytoestrogen Coumestrol, a synthetically produced phytoestrogen, on the development of CAV and the degree of fibrosis in an ovariectomized female heterotopic chronic allograft model (LEW-F344).. We found that, 150 days after transplantation, no significant effect of estrogen application on intimal thickening of coronary arteries was observed. 17beta-estradiol and phytoestrogen Coumestrol did significantly reduce the perivascular immune reaction. However, the immune effect had no consequence on the intensity of CAV. Although neither 17beta-estradiol nor phytoestrogen Coumestrol revealed a positive effect on CAV, the group of animals treated with 17beta-estradiol showed the highest decline in heart function and the most distinct fibrosis.. 17beta-estradiol does not affect CAV positively, but worsens cardiac allograft function and leads to increased fibrosis. This is the first study showing a negative effect of 17-beta-estradiol after heart transplantation in the long term.

Topics: Animals; Body Weight; Coumestrol; Disease Models, Animal; Estradiol; Female; Heart Transplantation; Phytoestrogens; Postoperative Complications; Rats; Rats, Inbred F344; Rats, Inbred Lew; T-Lymphocytes; Transplantation, Homologous; Transplantation, Isogeneic; Uterus; Weight Gain

Equol, a derivative of daidzein produced by enterobacteria, has greater activity as a phyto-oestrogen compared with daidzein. Difructose anhydride III (DFAIII) is a newly manufactured non-digestible disaccharide with unique fermentation properties. The present study evaluated the prebiotic effects of DFAIII on equol production and on plasma cholesterol concentrations related to the changes in equol production. We compared plasma equol concentrations at 10.00 and 18.00 hours and faecal isoflavone excretion in three groups of seven rats (male Wistar-ST strain, 6 weeks old) fed a basal diet or a DFAIII or fructooligosaccharide (15 g/kg diet) diet containing 1 g soya isoflavones/kg diet for 20 d. Equol concentrations in the DFAIII group were higher than in the control and fructooligosaccharides groups, especially in the later phase of the light period (18.00 hours) throughout the experiment. Daizein and genistein concentrations did not change between the diet groups. The faecal ratios of equol:daidzein were very high in all groups, but the ratios were higher in the DFAIII group than the control and fructooligosaccharide groups on day 3, and this tendency continued throughout the experiment. On day 20, the plasma total cholesterol concentration was lowest in the DFAIII group. Additionally, the cholesterol concentrations were inversely correlated to plasma equol concentration in all the rats. In conclusion, DFAIII efficiently enhanced plasma equol concentrations, which may be associated with an increase in equol production and a decrease in equol degradation by enterobacteria. Higher plasma equol concentrations may contribute to the hypocholesterolaemic effect of DFAIII feeding.

Topics: Animals; Body Weight; Cecum; Cholesterol; Diet; Dietary Supplements; Disaccharides; Equol; Feces; Genistein; Isoflavones; Male; Oligosaccharides; Phytoestrogens; Rats; Rats, Wistar

The neural control systems for the ovulatory cycle and lordosis behavior are sexually differentiated by estrogen during the perinatal period in rats. In the present study, the effects of a single neonatal injection with the phytoestrogen, coumestrol, on female reproductive functions were investigated. Female rats were injected subcutaneously with 1 or 3mg coumestrol (CM1, CM3), 1mg genistein (GS1), 1mg estradiol (E2), or oil at day 5 after birth (birth day=day 1) and an estrous cycle check and lordosis behavior test were performed. As a result, vaginal opening was advanced in CM1-, CM3- or E2-treated females. A vaginal smear check indicated that oil- or GS1-treated females showed a constant 4- or 5-day estrous cycle, whereas CM1-, CM3- or E2-treated rats showed a persistent or prolonged estrus. Ovariectomy was performed in all females at 60 days of age. The ovary weights in the CM1-, CM3- or E2-treated groups were lower than those in the oil- and GS1-treated groups and no corpora lutea were found in any rats of these three groups, except for two E2-treated rats. Behavioral tests were carried out after implantation of E2-tubes. All rats in the CM1-, GS1-treated groups showed a high lordosis quotient (LQ), being comparable to that in the oil-treated females. On the other hand, LQs in the CM3, E2 or male groups were lower than that in the control female group. These results suggest that a single neonatal injection of 3 mg coumestrol was effective in suppressing the functions of ovulation-inducing mechanisms and the induction of lordosis, but 1mg coumestrol was effective in only the estrous cycle of female rats.

Topics: Animals; Animals, Newborn; Behavior, Animal; Body Weight; Contraceptives, Oral, Combined; Coumestrol; Dose-Response Relationship, Drug; Estradiol; Estrous Cycle; Ethynodiol Diacetate; Female; Male; Mestranol; Organ Size; Ovariectomy; Phytoestrogens; Posture; Pregnancy; Rats; Rats, Wistar; Sexual Behavior, Animal; Time Factors; Vagina

Genistein is a phytoestrogen that occurs naturally in the diet, especially in soy-based foods. There is widespread interest in phytoestrogens as chemopreventive agents for a variety of diseases and cancers based on epidemiologic evidence. Although soy and its constituents, such as genistein, have been consumed at high levels in several Asian populations without apparent adverse effects, concern has been raised about potential adverse effects due to estrogenic and other activities. The subchronic and chronic safety of genistein were evaluated in the beagle dog including a 4-week study and a 52-week safety study with a 13 week interim sacrifice and a 4 week recovery period. In both studies at doses of 50, 150 and 500 mg/kg/day, genistein was well tolerated. In the 4 week study, except for an increase in uterine weights in female dogs at 500 mg/kg/day, there were no other treatment related findings. In the 52-week study, the primary effects of genistein were observed on the reproductive tract, which included for male dogs: reduced size and/or weight of the testes, epididymus and prostate of 2/2 dogs after 13 weeks of treatment and in 1/4 dogs after 52 weeks of treatment at 500 mg/kg/day. The histological changes observed in the affected dogs at 500 mg/kg/day indicated atrophy of the testes and prostate gland and absent spermatozoa in the epididymus. At the mid-dose of 150 mg/kg/day, although there was a reduction to a lesser extent in testes weight after 13, but not 52 weeks, there were no histopathological changes. In female dogs, the reproductive tract effects included increased uterine weight at 500 mg/kg/day after 13 weeks of treatment, but not after 52 weeks of treatment. There was also a small decrease in ovarian weights at 150 and 500 mg/kg/day after 13 weeks and at 500 mg/kg/day after 52 weeks of treatment. There were no histopathological correlates to the changes in organ weights in female dogs. In the 4-week recovery group dogs, no changes were observed in dogs previously treated for 52 weeks with 500 mg/kg/day of genistein. It is concluded that the administration of genistein to dogs for a period of 4-52 weeks was well tolerated and did not result in systemic toxicity. Effects of genistein on the reproductive tract at very high doses were functional in nature and are of a type that would be expected in view of the relatively weak estrogenic activity of genistein and were considered not adverse effects. In the 4-week study, the no observed adverse

Topics: Animals; Atrophy; Blood Cell Count; Blood Chemical Analysis; Body Weight; Capsules; Diet; Dogs; Dose-Response Relationship, Drug; Female; Genistein; Genitalia, Male; Male; No-Observed-Adverse-Effect Level; Organ Size; Phytoestrogens; Testicular Diseases; Tissue Distribution

The extent of conversion of daidzein to its metabolite, equol, by intestinal microflora may be a critical step that determines if a diet rich in daidzein protects against the deterioration of bone after estrogen withdrawal. The objective was to determine the extent that daidzein is converted to equol. In addition, bone mineral content (BMC), bone mineral density (BMD) and strength of femurs and lumbar vertebrae (LV) in four mouse strains were measured. Mice were ovariectomized and fed control diet (AIN93G) with or without daidzein (200 mg daidzein/kg diet) for 3 weeks, after which serum, femurs and LV were collected. Serum daidzein and equol were elevated in all mice fed daidzein. Among mice fed daidzein, the CD-1 and Swiss-Webster (SW) mice had higher (P<.001) serum equol than C57BL/6 (C57) and C3H mice. Differences due to mouse strain were observed for all bone outcomes. C57 mice had lower femur BMC (P<.001), BMD (P<.001) and peak load at femur midpoint (P<.001) and neck (P<.001) than other mouse strains. C57 mice also had a lower femur midpoint yield load (P<.001) and resilience (P<.001) than C3H mice. C57 mice had a lower LV1-4 BMC (P<.001) and BMD (P<.001) compared with all mouse strains and peak load of LV3 was lower than CD-1 and SW mice. Differences in serum equol, BMD and bone strength properties should be considered when selecting a mouse strain for investigating whether dietary strategies that include isoflavones preserve bone tissue after ovariectomy.

Topics: Animals; Biomechanical Phenomena; Body Weight; Bone and Bones; Bone Density; Eating; Equol; Female; Femur; Isoflavones; Lumbar Vertebrae; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Ovariectomy; Phytoestrogens; Species Specificity

Plant secondary metabolites with estrogenic activity (phyto-estrogens) have been studied in the past as a potential alternative to classical hormone-replacement therapy (HRT) in menopausal women. No final verdict on the efficacy of soy or red clover based pharmaceutical preparations has been reached despite numerous clinical studies. We have studied the novel and most potent phyto-estrogen 8-prenylnaringenin (8-PN) in adult ovariectomized rats, an established animal model to mimic hormone dependent osteoporosis in menopausal women. Our results demonstrate that 8-PN can completely protect from ovariectomy induced bone-loss while exhibiting minimal, (dose independent) trophic effects on uterus and endometrium. It is estimated that at equivalent bone protective doses of 17beta-estradiol and 8-PN, the phyto-estrogen has a 10-fold lower stimulatory effect on uterus and endometrium. The bone tissue specific effect of 8-PN was confirmed in a transgenic reporter mouse model (ERE-Luc mice). Here we also found pronounced estrogenic activity in prostate. Present results add important aspects to the pharmacological profile of 8-PN and position this compound as an interesting alternative new candidate for treatment of peri- and postmenopausal symptoms.

Topics: Animals; Body Weight; Bone Density; Epithelium; Estradiol; Female; Flavanones; Humans; Male; Mice; Mice, Transgenic; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Prostate; Rats; Rats, Sprague-Dawley; Uterus

To investigate the functional changes in rabbit penile corpus cavernosum (CC) secondary to experimental hyperestrogenism and attempt to identify sites of immunoexpression for estrogen receptor subtypes alpha and beta (ER-alpha and ER-beta) in the CC. Although the role of testosterone in sexual function has been extensively studied in clinical settings and experimental animal models, the effect of hormonal modulation/imbalance arising from estrogenic excess has not been characterized.. Eighteen New Zealand white male rabbits (2.5-3.0 kg) were divided into control and two treatment groups. The two treatment groups were given orally 0.1 mg of estradiol valerate (estradiol group) or phytoestrogen, daidzein (phytoestrogen group) daily for 12 weeks. Blood and tissue samples were collected for hormone levels and in vitro pharmacologic studies. CC samples from untreated rabbits (n = 4) were cryosectioned and incubated with appropriate mouse monoclonal antibody for identification of ER-alpha and ER-beta.. Through immunohistochemistry, color signals for nuclear ER-alpha and ER-beta receptors were localized within the CC. Chronic treatment with estradiol and phytoestrogen significantly reduced the systemic total testosterone levels. In organ bath experiments, relaxant responses to acetylcholine, nitroglycerin, and nitrergic transmission were significantly attenuated compared with the control response. With regard to the contractile effect, both types of estrogen treatments significantly potentiated norepinephrine-induced antierectile contraction of the CC.. These results indicate that estradiol treatment and chronic exposure of phytoestrogen may cause receptor-mediated pathophysiologic changes in erectile function, leading to erectile dysfunction.

Topics: Acetylcholine; Animals; Body Weight; Estradiol; Estrogen Receptor alpha; Estrogen Receptor beta; Isoflavones; Male; Muscle, Smooth; Nitric Oxide Donors; Nitroglycerin; Penile Erection; Phytoestrogens; Plant Preparations; Rabbits; Receptors, Estrogen; Testosterone; Vasodilator Agents

Recently, the finding of high plasma concentration of phyto-oestrogens in soy protein formula (SPF) fed children has focused scientific attention on the phyto-oestrogens (isoflavones genistein, daidzein, and their glycosides) contained in SPFs. The aim of this study was to evaluate some hormonal and metabolic effects of long-term (more than 6 months) SPF feeding. We enrolled 48 children, mean age 37 months (range 7-96 months), 27 males and 21 females. All children underwent physical examination. Bone age, urinary markers of bone metabolism, serum levels of bone alkaline phosphatase, osteocalcin, 17beta-oestradiol, and intact parathyroid hormone were measured. Eighteen healthy children represented the control group. No abnormalities were observed in auxological parameters; none of the enrolled girls showed signs/symptoms of precocious puberty and none of the boys presented gynecomastia; bone age was within the normal range. The serum level of bone alkaline phosphatase, osteocalcin, 17beta-oestradiol, and intact parathyroid hormone, and the urinary levels of the markers of bone metabolism were all within normal values. We conclude that long-term feeding with SPFs in early life does not seem to produce oestrogen-like hormonal effects.

Topics: Body Height; Body Weight; Bone and Bones; Bone Development; Child; Child, Preschool; Female; Food, Formulated; Genitalia; Gynecomastia; Hormones; Humans; Infant; Infant Food; Isoflavones; Male; Phytoestrogens; Plant Preparations; Puberty, Precocious; Retrospective Studies; Sexual Maturation; Soybean Proteins

We previously found that effects of perinatal dietary exposure to ethinylestradiol (EE) on the rat reproductive system differ depending on the diet used, with a more pronounced estrogenic impact with a regular diet that includes soy-derived proteins than with a soy-free (SF) diet. The present study was performed to examine whether genistein (GEN), a soy-derived major phytoestrogen, acts synergistically with EE. Maternal rats were fed SF diet without chemical (control) or containing 0.5-ppm EE, 0.5-ppm EE + 100-ppm GEN, 0.5-ppm EE + 1250-ppm GEN, or 1250-ppm GEN, from gestational day 15 to postnatal day (PND) 11. EE reduced serum testosterone in males at PND 3, and affected the onset of puberty of both sexes and estrous cyclicity and reproductive system in females, irrespective of co-administration of GEN. GEN alone also affected estrous cyclicity and the reproductive system in females. However, no combination effects of GEN with EE were evident, suggesting no synergism between the two.

Topics: Administration, Oral; Adrenal Glands; Animals; Body Weight; Epididymis; Estrogens; Estrous Cycle; Ethinyl Estradiol; Female; Genistein; Litter Size; Male; Ovary; Phytoestrogens; Pituitary Gland; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred Strains; Reproduction; Sex Differentiation; Testis; Testosterone; Uterus

The aim of this study was to evaluate the effects of Sedum sarmentosun Bunge (SS) on the lipid on serum and the collagen content of the connective tissues in ovariectomized estrogen-deficient rats. Three groups were surgically ovariectomized. The fourth group was sham operated. From day 2 until day 37 after the ovariectomy, Sprague-Dawley female rats were randomly assigned to the following groups: sham-operated rats (sham), ovariectomized control rats (OVX-control), ovariectomized rats supplemented with an ethyl ether fraction of SS at 10 mg/kg bw/d (OVX-EE), ovariectomized rats supplemented an ethyl acetate fraction of SS at 10 mg/kg bw/d (OVX-EA). The SS fractions were orally administrated at 1 mL per day. The estrogenic effects of the ethyl ether and ethyl acetate fractions of SS, were investigated using one in vitro assay and two in vivo assays. The treatment of the partition of the ethyl ether and ethyl acetate layers of SS increased the transcriptional activity 0.7-fold and 0.5-fold compared to those that were given 17beta-estradiol treatment, respectively. The OVX rats were significantly heavier than the sham-operated rats at all times, but supplementation with the SS extracts tended to result in less weight gain than OVX-control. The serum triglyceride levels were significantly decreased after supplementation with the SS portion EE and EA layers. Supplementation with the SS extracts prevented a decrease in the collagen level in bone and cartilage tissues. This result indicates that the SS affects the collagen synthesis in ovariectomized rats. These results are consistent with the conclusions based on the estrogenic activities of SS. Therefore, it may be used to possibly improve the quality of life in menopausal women.

Topics: Acetates; Animals; Body Weight; Breast Neoplasms; Estradiol; Ether; Female; Humans; Isoflavones; Organ Size; Ovariectomy; Phytoestrogens; Plant Extracts; Plant Preparations; Rats; Rats, Sprague-Dawley; Sedum; Triglycerides; Tumor Cells, Cultured; Uterus

The effects of Lactobacillus gasseri JCM 1131(T) on isoflavonoid levels within the caecum and plasma were assessed in adult mice. Male 5-week-old mice were fed an AIN 93M diet for 30 d. Two groups of mice were administered either L. gasseri JCM 1131(T) (the LGI group) or physiological saline solution (the control (CI) group) daily for 5 d before dissection. The plasma daidzein concentration was significantly higher in the LGI group, however, their plasma equol concentration was significantly less than in the CI group. The total amount of equol present as aglycone in the caecum was significantly greater in the CI group, but there was no significant difference in the total daidzein present as caecal aglycone. In an in vitro incubation of daidzein with the faecal flora of mice, the equol concentration was significantly higher in the CI group. The numbers of lactobacilli present were significantly higher in the LGI group. The present data suggest that the administration of L. gasseri is likely to influence the effect of isoflavonoids on the host via changes in the gastrointestinal environment.

Topics: Animals; Body Weight; Cecum; Colony Count, Microbial; Eating; Equol; Isoflavones; Lactobacillus; Male; Mice; Mice, Inbred ICR; Phytoestrogens

Soyfoods contain estrogenic isoflavones--namely, genistein (G) and daidzein (D)--that, like estrogens, display physiological effects in humans and animals. Previously we and others have demonstrated antioxidant and cardioprotective effects of orally ingested soy diets and soy isoflavones. The overall objective of this study was to test the effects of injected soy isoflavones, G and D, on liver lipids, liver free radical scavenger systems, and parameters of cardiovascular risk. Forty male rats were injected with G, D, estradiol (E), or a vehicle control (V) for 6 weeks. At the end of the study, body weight, food intake, feed efficiency ratio (FER), plasma glucose and cholesterol, abdominal fat pad weight, reproductive organ weight, liver weight, liver lipids, and liver free radical scavenger systems were compared. Food intake was significantly (P < .04) higher in the D-, G-, and E-treated animals compared with V-treated animals. FER was lower (P < .001) in D-, G-, and E-treated animals compared with the V- and the E-treated animals. Body weight, testis weight, and prostate weight were markedly (P < .001) lower in the E-treated animals compared with D-, G-, and V-treated animals. Intraabdominal fat pad weights were also significantly (P < .001) lower in the E group, although this effect was lost when corrected for body weight. Liver weights were considerably lower in the D-, G-, and E-treated animals versus the V group (P < .001). Total plasma cholesterol was reduced (P < .05) in D- and E-treated animals versus the V group. Liver lipids appeared to be unchanged by the isoflavones and slightly elevated by E treatment (P < .02). Liver catalase levels were numerically higher in the D- and E-treated animals compared with the V group (P < .1). Similarly, Cu/Zn superoxide dismutase (SOD) activity was significantly elevated in the D and E groups (P < .01), while G treatment (P < .03) elevated SOD to a lesser degree, versus the V group. These results suggest that subcutaneous injections of the naturally occurring soy isoflavone D and, to a lesser extent, G exert cardioprotective effects and stimulate antioxidant systems, while minimizing the undesirable effects elicited by E treatment.

Topics: Animals; Body Weight; Catalase; Cholesterol; Estradiol; Free Radical Scavengers; Genistein; Injections, Subcutaneous; Isoflavones; Lipid Metabolism; Lipids; Liver; Male; Organ Size; Phytoestrogens; Random Allocation; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

Estrogens exhibit complex but beneficial effects on brain structure, function and behavior. Soy-derived dietary phytoestrogens protect against hormone-dependent and age-related diseases, due to their estrogen-like hormonal actions. However, the effects of phytoestrogens on brain and behavior are relatively unknown. This study examined the influence of exposing male Long-Evans rats (lifelong) to either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet on body weights, behavioral pain thresholds, the hypothalamic-pituitary-adrenal (HPA) hormonal stress response, hippocampal glucocorticoid receptor and brain neural cell adhesion molecules (NCAM) and synaptophysin levels using standard behavioral and biochemical techniques. Body weights were significantly decreased in Phyto-600 fed animals compared to Phyto-free values. There were no significant changes in behavioral pain thresholds, circulating corticosterone concentrations (after acute immobilization stress) or NCAM and synaptophysin levels in various brain regions by the diet treatments. However, Phyto-600 fed males displayed significantly higher plasma adrenocorticotrophin (ACTH) (post-stress) and hippocampal glucocorticoid receptor levels vs. Phyto-free values. These data suggest that (1) body weights are significantly reduced by soy-derived phytoestrogens, (2) behavioral pain thresholds (via heat stimuli) are not influenced by dietary phytoestrogens, but (3) these estrogenic molecules in the hippocampus enhance glucocorticoid receptor abundance and alter the negative feedback of stress hormones towards a female-like pattern of higher ACTH release after activation of the HPA stress axis. This study is the first to show that lifelong consumption of dietary phytoestrogens alters the HPA stress response in male rats.

Topics: Adrenocorticotropic Hormone; Animals; Blotting, Western; Body Weight; Brain; Corticosterone; Estrogens, Non-Steroidal; Hippocampus; Isoflavones; Male; Neural Cell Adhesion Molecules; Pain Threshold; Phytoestrogens; Plant Preparations; Rats; Rats, Long-Evans; Receptors, Glucocorticoid; Soybean Proteins; Stress, Physiological; Synaptophysin

The aim of this study was to analyse the multigenerational effects of para-nonylphenol (NP) and resveratrol (RES) on the body weight, organ weight and reproductive fitness of outbred CD-1 mice. The data indicate that in male mice, NP had an effect on the weight of selected reproductive organs and the kidneys in the parental (P) generation males. Effects on selected reproductive organs, the liver and kidneys in the F1-generation males were also seen. In females, effects of NP on body weight and kidney weight were seen in the P generation, but no effects on any measured parameter were seen in the F1 generation. RES had no effect on body weight but did have some effect on selected male and female reproductive organs in the P generation. RES altered the spleen and liver weights of P-generation males and the kidney weight of F1-generation males. Acrosomal integrity (using a monoclonal antibody against intra-acrosomal sperm proteins) was assessed for both generations of NP- and RES-treated mice. A significant reduction in acrosomal integrity was seen in both generations of NP-treated, but not in RES-treated, mice. Fewer offspring were observed in the second litter of the F2 generation of mice treated with NP; no similar effect was seen in RES-treated mice. The litter sex ratio was not different from controls. Unlike RES, NP had a negative effect on spermatogenesis and sperm quality with a resultant impact on in vivo fertility.

Topics: Acrosome; Animals; Animals, Outbred Strains; Body Weight; Environmental Pollutants; Female; Fertility; Genitalia, Female; Genitalia, Male; Infertility, Male; Isoflavones; Kidney; Litter Size; Liver; Male; Mice; Organ Size; Ovarian Follicle; Phenols; Phytoestrogens; Plant Preparations; Pregnancy; Resveratrol; Sex Ratio; Spermatogenesis; Stilbenes

M. Sakaue et al. (2001,J. Occup. Health vol. 43, pp. 185-190) have described how oral exposure of sexually mature male rats to bisphenol A (BPA) between postnatal days (PND) 91-97 led to a reduction in daily sperm production (DSP) 5 weeks later (18 weeks of age). Activity was observed over the dose range 20 microgram/kg-200 mg/kg BPA, with an absence of activity over the dose range 2 ng/kg-2 microgram/kg BPA. There was no evidence of a dose response relationship over the active dose range (five orders of magnitude range). The observation of endocrine disruption (ED) effects for BPA at such low doses, and in sexually mature animals, was unexpected. It was therefore decided to mount an independent repeat of their study. A total of four independent studies were conducted according to the protocol used by Sakaue et al. Doses of 20 microgram/kg, 2 mg/kg, or 200 mg/kg BPA were administered to adult Sprague-Dawley (SD) rats over PND 91-97, and the studies were terminated when the rats reached the age of 18 weeks. Three different rodent diets were employed (RM3, Purina 5002, and CE2), the last of which had been used by Sakaue et al. BPA failed to give any evidence of ED activities, including the changes in DSP reported by Sakaue et al. 2001. During the course of these studies, the test protocol was adapted to coincide more precisely with that used by Sakaue et al.; this included restricting the number of animals per cage, removing bedding from the cages, and changing to the use of glass water bottles in the cages. The only thing of interest to emerge from our studies was the observation of a significant difference in DSP between the control groups of our first and second study. As the change in diet from RM3 to Purina 5002 was the major difference between those two studies, we conducted a repeat of the second study, but we were unable to confirm the differences seen between the first and second study. The probability that those differences arose either by chance, or as the result of intrinsic study-to-study variability, was strengthened by the absence of significant differences in the sperm parameters in a final (fifth) study where the sperm parameters for control animals maintained on the three different diets were compared under the conditions of the main experiments. No explanation for our failure to replicate the effects reported by Sakaue et al. is evident. A review of DSP values reported in the recent literature is provided and discussed, and it is conclude

Topics: Animals; Benzhydryl Compounds; Body Weight; Diet; Endocrine Glands; Estrogens, Non-Steroidal; Female; Intubation, Gastrointestinal; Isoflavones; Male; Organ Size; Phenols; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Spermatogenesis; Testis; Uterus

The putative skeletal effects of dietary soy phytoestrogens (SPE) were examined in comparison with those of conjugated equine estrogens (CEE; Premarin) in a 3-yr longitudinal study in ovariectomized female monkeys. Controls received alcohol-extracted soy protein with low phytoestrogen content, and treatment groups received either CEE (admixed into the control diet) or unextracted soy protein isolate containing SPE. The acknowledged bone protective effect of CEE was reflected by higher bone mass (by dual energy x-ray absorptiometry) and lower bone turnover marker levels. In contrast, control and SPE groups lost significant lumbar spine bone mineral content and density and whole body bone mineral content within the first year, resulting in reduced bone mass for both groups compared with CEE (P < 0.0005). No effect of SPE was observed for any bone mass measure (P > 0.44), although transient, estrogen-like effects of SPE on serum alkaline phosphatase, calcium, and C-terminal cross-link of type I collagen were observed at 3 months (P < 0.02). These results suggest that SPE may be poor substitutes for mammalian estrogens in protecting against bone loss resulting from estrogen deficiency.

Topics: Animals; Biomarkers; Body Weight; Bone and Bones; Bone Diseases, Metabolic; Densitometry; Diet; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Macaca fascicularis; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Preparations

The major object of this study was to characterize the effect of prepubertal trans-3,4',5-trihydroxystilbene (resveratrol) exposure on N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats. Prepubertal rats (15 to 19 days of age) were treated daily with either 10 or 100 mg/kg resveratrol for 5 days, and were compared with resveratrol-untreated animals (30 rats in each group). Six rats in each group were autopsied at 49 days of age, and their growth was evaluated. All remaining rats were given 50 mg/kg MNU, followed by monitoring for occurrence of mammary carcinoma. A dose of 100 mg/kg (but not 10 mg/kg) resveratrol significantly increased incidence of rat with mammary carcinomas > or =1 cm and multiplicity (all histologically detected mammary carcinomas per rat), but did not affect latency, compared with untreated controls. Resveratrol did not affect body weight increase, but 100 mg/kg resveratrol caused slightly earlier vaginal opening. Although all rats cycled, resveratrol-treated animals exhibited significantly increased irregularity of estrous cycle, spending more time in the estrus phase. Thus, short resveratrol treatment of prepubertal female rats affected endocrine function, and accelerated development of MNU-induced mammary carcinomas.

Topics: Age Factors; Alkylating Agents; Animals; Body Weight; Dose-Response Relationship, Drug; Estrous Cycle; Female; Isoflavones; Mammary Neoplasms, Experimental; Methylnitrosourea; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes

The objective of this study is to examine the effects of genistein on endothelial dysfunction in bilateral ovariectomized rats. Female Wistar rats were subjected to a bilateral ovariectomy (OVX rat). The animals were divided into three groups: sham treated with vehicle (DMSO 100 microliters/day, Shamveh), OVX treated with vehicle (DMSO 100 microliters/day, OVXveh), and OVX treated with genistein (0.25 mg/kg BW/day, OVXgen). Mean arterial pressure (MAP), heart rate (HR), body weight (BW), uterine weight and plasma E2 were monitored at 4-week after the treatment. We investigated the endothelium-dependent and -independent vasorelaxation by using acetylcholine (Ach 10(-6) M) and sodium nitroprusside (SNP 10(-7) M), respectively. The experimental results indicated that the uterine weights of all OVX rats were significantly decreased as compared to the sham groups (OVXveh = 0.007+/-0.004 g, OVXgen =0.003+/-0.001 g, Shamveh =0.017+/-0.001 g). MAP of OVXveh group was significantly increased compared to the Sham group (OVXveh=139.99+/-7.50 mmHg, Shamveh =118.10+/-19.33 mmHg, p<0.05). No significant increase in MAP was observed in OVXgen (OVXgen =123.33+/-8.61 mmHg; p<0.05). HR showed no significant difference among those groups. The present study of vasodilator responses demonstrated only the significant decrease in endothelium-dependent, not for endothelium-independence, in OVX rats, while the treatment of genistein could significantly attenuate this abnormality (OVXveh =3.03+/-3.99%, Shamveh =45.46+/-3.59%, OVXgen =33.52+/-3.25% in % change of vessel diameter). The present findings suggest that genistein could be used as a therapeutic agent for menopausal vascular complications.

Topics: Acetylcholine; Animals; Blood Pressure; Body Weight; Drug Evaluation, Preclinical; Endothelium, Vascular; Estradiol; Female; Genistein; Heart Rate; Ileum; Isoflavones; Nitroprusside; Norepinephrine; Organ Size; Ovariectomy; Phytoestrogens; Plant Preparations; Rats; Rats, Wistar; Splanchnic Circulation; Uterus; Vasodilation

Angiogenesis is important in tumor growth, progression and metastatic dissemination. Vascular endothelial growth factor (VEGF) is one key factor in promotion of breast cancer angiogenesis. VEGFs are bioactive in the extracellular space where they become available to the endothelial cells. Phytoestrogens such as lignans have been shown to alter breast cancer incidence and be cancer-protective in rats. We show that supplementation of 10% flaxseed, the richest source of mammalian lignans, to nude mice with established human breast tumors reduced tumor growth and metastasis. Moreover, flaxseed decreased extracellular levels of VEGF, which may be one mechanistic explanation to the decreased tumor growth and metastasis.

Topics: Animals; Body Weight; Down-Regulation; Endothelial Growth Factors; Estrogens, Non-Steroidal; Extracellular Space; Female; Flax; Humans; Intercellular Signaling Peptides and Proteins; Isoflavones; Lung Neoplasms; Lymphatic Metastasis; Lymphokines; Mammary Neoplasms, Experimental; Mice; Mice, Nude; Neoplasm Transplantation; Phytoestrogens; Plant Preparations; Seeds; Transplantation, Heterologous; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To investigate the influence of phyotestrogens in the diet, an immature uterotrophic assay of ethinylestradiol, bisphenol A, 4-nonylphenol or genistein was performed in rats given the formula MF diet, modified NIH-07 open formula diet, or modified NIH-07 phytoestrogen-lowered-diet (study 1). The chemicals were administered subcutaneously from 20 days of age for 3 days. Doses of ethinylestradiol, bisphenol A, 4-nonylphenol or genistein were 0.06-0.6 micro g/kg per day, 1-10 mg/kg per day, 10-100 mg/kg per day or 1-20 mg/kg per day, respectively. In another study, an immature uterotrophic assay of genistein and ethinylestradiol together with ICI 182,780 or antide was performed to compare the ovarian changes with these chemicals (study 2). Doses of genistein or ethinylestradiol were 30 mg/kg per day or 0.6 micro g/kg per day, respectively, and these chemicals were injected subcutaneously from 20 days of age for 3 days. In study 1, there were no essential differences in the uterus weights among the various phytoestrogen-content diets. In study 2, the ovary weights in rats given genistein were significantly higher than in the controls, whereas the ovary weights in rats given ethinylestradiol were lower than in the controls. The ovary weights in the ICI 182,780 plus genistein group were significantly higher than in the genistein group, but decrease of the ovary weights was detected in the antide plus genistein group. There was no significant difference in ovary weights between the ICI 182,780 plus ethinylestradiol group and the ethinylestradiol group, but decrease of ovary weights was detected in antide plus ethinylestradiol group. In a histological examination of the ovary, fluid-filled follicles in the genistein group were more numerous than in other groups and increase of granulosa cell fragmentation was seen in the ethinylestradiol and other groups with the exception of the genistein group. The present findings demonstrate that the sensitivity of the immature rat uterotrophic assay is not influenced by the relatively low level of phytoestrogen in diets and that the ovarian changes occurring with genistein and ethinylestradiol are different.

Topics: Animals; Benzhydryl Compounds; Body Weight; Dose-Response Relationship, Drug; Estradiol; Estrogens, Non-Steroidal; Ethinyl Estradiol; Female; Fulvestrant; Genistein; Isoflavones; Oligopeptides; Organ Size; Ovary; Phenols; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Uterus

Phytosterols or plant sterols (PS) are consumed as natural remedies and margarines by the general population in developed countries to lower elevated serum cholesterol levels. They are also present in high concentrations in pulp mill effluents. The aim of the study was to screen the endocrine and metabolic parameters of the European polecat (Mustela putorius) for the effects of PS. The results showed an increase in the plasma estradiol and TH levels with no effects on the hypophyseal regulatory hormones. The plasma ghrelin levels decreased. PS also affected intermediary metabolism. The liver glycogen content increased as did the kidney glucose-6-phosphatase activity. The liver lipase esterase activity, on the other hand, decreased due to PS. In serum lipids the total cholesterol did not change, but the low-density lipoprotein levels increased and the high-density lipoprotein-cholesterol ratio decreased. PS had widespread previously unreported effects on the physiology of the polecat. The multiple effects indicate the need of a thorough risk assessment of the effects and interactions of PS.

Topics: Animals; Body Weight; Carnivora; Dose-Response Relationship, Drug; Endocrine Glands; Estradiol Congeners; Estrogens, Non-Steroidal; Female; Glycogen; Hormones; Hypolipidemic Agents; Inactivation, Metabolic; Isoflavones; Kidney; Lipids; Liver; Male; Metabolism; Organ Size; Phytoestrogens; Phytosterols; Plant Preparations; Sitosterols

Resveratrol is a phytoestrogen naturally found in grapes and is a major constituent of wine thought to exert both cardioprotective and chemopreventive activities. Recent studies show that this bioflavonoid binds to and activates gene transcription via the estrogen receptor (ER) subtypes ERalpha and ERbeta. Previous studies have focused primarily on the in vitro effects of resveratrol (RES) in estrogen-sensitive tissues or in carcinogenic cell lines, while frequently neglecting to document its potential effects in animal models with intact neuroendocrine systems. However, the present studies were designed to systematically characterize the in vivo effects of RES on reproductive physiology and behavior in adult female rats. In gonadally intact females, RES consumption reduced body weight, disrupted estrous cyclicity, and induced ovarian hypertrophy. However, in ovariectomized females RES (10-1000 microg) injections did not appear to mimic 17 beta-estradiol benzoate (EB)-induced behavioral responses and had no lasting effects on subsequent estrogen sensitivity or sociosexual behavior. The present studies support recent in vitro findings that RES differs from other phytoestrogens by acting as a possible mixed agonist/antagonist, depending on the availability of specific ER isoforms localized in the reproductive tract and brain of the female rat.

Topics: Animals; Body Weight; Dose-Response Relationship, Drug; Estradiol; Estrogens; Estrogens, Non-Steroidal; Estrous Cycle; Female; Isoflavones; Organ Size; Ovariectomy; Ovary; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Reproduction; Resveratrol; Sexual Behavior, Animal; Stilbenes; Uterus; Vagina

We evaluated the mechanism of action by the phytoestrogen genistein in the prepubertal rat uterus, when administered pharmacologically or physiologically. Female rats were injected with genistein (500 microg/g body weight), estradiol benzoate (EB) (500 ng/g body weight) or vehicle, dimethylsulfoxide (DMSO), on days 16, 18, and 20 postnatal. In 21-day-old rats, both compounds increased circulating estradiol and decreased progesterone concentrations. Uterine estrogen receptor alpha (ER-alpha) and androgen receptor (AR) proteins were reduced, and progesterone receptors (PR) were increased, as measured by western blot analyses. Immunohistochemistry for ER-alpha was confirmatory. Reverse transcription-polymerase chain reaction (RT-PCR) analyses indicated a decrease in ER-alpha, but not in ER-beta, PR and AR mRNA levels following genistein treatment. In prepubertal rats exposed perinatally to 250 mg genistein per kg AIN-76A diet or 250 microg estradiol per kg diet, uterine ER-alpha, AR, and PR proteins were not altered significantly. We conclude that pharmacologic, but not physiologic concentrations of genistein can modulate sex steroid receptor expression in the rat uterus.

Topics: Animals; Body Weight; Estradiol; Estrogens, Non-Steroidal; Female; Gene Expression Regulation; Genistein; Immunohistochemistry; Isoflavones; Organ Size; Ovariectomy; Ovary; Phytoestrogens; Plant Preparations; Progesterone; Rats; Rats, Sprague-Dawley; Receptors, Steroid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sexual Maturation; Testosterone; Uterus

It has been shown recently that alpha-zearalenol, a resorcyclic acid lactone, prevents bone loss in a rat model of postmenopausal bone loss. We have therefore investigated the effects of this phytoestrogen on endothelial dysfunction induced by estrogen deficiency in rats. Female mature Sprague-Dawley rats underwent a bilateral oophorectomy (OVX rats). Sham-operated animals (sham OVX rats) were used as controls. Three weeks after surgery, animals were randomized to the following treatments: alpha-zearalenol (1 mg/kg/day, i.m., for 4 weeks), 17beta-estradiol (20 microg/kg/day, i.m., for 4 weeks), or their vehicle (100 microl, i.m., of cottonseed oil). Two other groups of rats were treated with alpha-zearalenol or 17beta-estradiol plus the pure estrogen receptor antagonist ICI 182780 (2.5 mg/kg/day, i.m., for 4 weeks). Mean arterial blood pressure (MAP), heart rate (HR), total plasma cholesterol, plasma estradiol, and plasma alpha-zearalenol were studied. We also investigated endothelial-dependent (acetylcholine, 10 nM to 10 microM) and endothelial-independent (sodium nitroprusside, 15 nM to 30 nM) relaxation of aortic rings, as well as N(G)-methyl-L-arginine (L-NMA: 10 to 100 microM)-induced vasoconstriction and calcium-dependent nitric oxide synthase (cNOS) activity in homogenates of lungs taken from both sham OVX rats and OVX rats. Untreated OVX rats had, compared with sham OVX animals, unchanged body weight, MAP, HR, and plasma cholesterol. In contrast oophorectomy reduced plasma estradiol levels (OVX, 2 +/- 0.5 pg/ml; sham OVX, 35 +/- 6 pg/ml), impaired endothelial-dependent relaxation and blunted L-NMA-induced contraction (L-NMA 100 microM: sham OVX, 2.7 +/- 0.3 g/mg tissue; OVX, 1.3 +/- 0.1 g/mg tissue). Moreover OVX rats showed a reduced calcium-dependent NO synthase (cNOS) activity. Treatment with alpha-zearalenol or with 17beta-estradiol reverted the endothelial dysfunction and increased cNOS activity in lung homogenates. These effects were abolished by the pure estrogen receptor antagonist ICI 182780. Our data suggest that alpha-zearalenol improves endothelial-dependent relaxation in OVX rats through an estrogen receptor-mediated effect.

Topics: Acetylcholine; Animals; Aorta; Blood Pressure; Body Weight; Endothelium, Vascular; Estradiol; Estrogen Antagonists; Estrogens, Non-Steroidal; Female; Fulvestrant; Heart Rate; In Vitro Techniques; Isoflavones; Lung; Muscle Contraction; Muscle, Smooth, Vascular; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroprusside; Organ Size; Ovariectomy; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Reference Values; Uterus; Zeranol

Phytoestrogens are extensively investigated for their potential to prevent many hormone-dependent cancers and age-related diseases, however little is known about their effects in brain. Brain aromatase and plasma phytoestrogen levels were determined in Sprague-Dawley rats fed a phytoestrogen-rich diet during pregnancy/lactation. Ingested phytoestrogens cross the placenta and become concentrated in maternal milk as evident from high infantile plasma concentrations. Dietary phytoestrogens, however, do not alter brain aromatase during pregnancy/lactation or perinatal development.

Topics: Animals; Animals, Newborn; Aromatase; Body Weight; Brain; Enzyme Activation; Estrogens, Non-Steroidal; Female; Food, Formulated; Glycine max; Hypothalamus, Middle; Isoflavones; Lactation; Male; Maternal-Fetal Exchange; Phytoestrogens; Plant Preparations; Pregnancy; Prenatal Exposure Delayed Effects; Preoptic Area; Rats; Rats, Sprague-Dawley; Sex Factors

Five rodent diets have been evaluated for their possible effect on the sexual development of the rat. Groups of 12 pregnant Alpk rats were fed one of the following combinations of diets during pregnancy and postnatally: RM3/RM1, AIN-76A/AIN-76A, RM3/AIN-76A, Teklad Global 2016 (Global)/Global and Purina 5001/Purina 5001. AIN-76A is phytoestrogen-free while the other diets contained varying amounts of phytoestrogens. The phytoestrogens genistein and daidzein were determined in the diets studied, and the concentrations found agreed with earlier estimates. RM3/RM1 was selected as the control group, as this has been used routinely in this laboratory for the past decade. Determinations were made in offspring of the times of vaginal opening and first estrus among the females, and of prepuce separation and testes descent among the males. At postnatal day (PND) 26 the females from 6 of the 12 litters were terminated and tissue weights measured. Males from 6 of the 12 litters were similarly studied at PND 68. Animals from the remaining litters were transferred to RM1 diet at PND 70. Termination of the study was at PND 128 (males) and PND 140 (females) when body weights and tissue weights were determined. Marked differences in body weight, sexual development, and reproductive tissue weights were observed for rats maintained on AIN-76A or Purina 5001, with only minimal effects among rats maintained on the Global diet. These comparisons were against RM3/RM1 as the reference diet. However, using Purina 5001 as the reference diet reversed the direction of the differences seen when using RM3/RM1 as the reference diet. The differences observed when using RM3/RM1 as reference diet occurred mainly postnatally. In addition, the fact that similar differences were seen for the phytoestrogen-free diet, AIN-76A, and the phytoestrogen-rich diet, Purina 5001, indicate that these effects are more likely to be caused by nutritional differences between the diets that then have centrally mediated effects on rodent sexual development, rather than individual dietary components affecting peripheral estrogen receptors (ER). This proposal is supported by abolition of the uterotrophic activity of AIN-76A and Purina 5001 (relative to RM3/RM1) in the immature rat by coadministration of the gonadotrophin-releasing hormone (GnRH) antagonist ANTARELIX: The present data indicate that choice of diet may influence the timing of sexual development in the rat, and consequently, that when evaluating

Topics: Age Factors; Animal Feed; Animals; Animals, Newborn; Biological Assay; Body Weight; Diet; Estrogens, Non-Steroidal; Female; Genistein; Isoflavones; Male; Oligopeptides; Organ Size; Phytoestrogens; Plant Preparations; Pregnancy; Rats; Rats, Inbred Strains; Rats, Wistar; Sexual Maturation; Weaning

Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets, exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body weight, consummatory behavior, and anxiety (as expressed in the elevated plus-maze). Phytoestrogens produced anxiolytic effects in both male and female Long-Evans rats. Additionally, phytoestrogens decreased body weight but increased consumption of food and/or water.

Topics: Androgens; Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Body Weight; Brain; Drinking; Eating; Estrogens; Estrogens, Non-Steroidal; Female; Food, Formulated; Glycine max; Isoflavones; Male; Maze Learning; Phytoestrogens; Plant Preparations; Rats; Rats, Long-Evans; Sex Characteristics

Naturally occurring estrogen-like molecules in plants (phytoestrogens), present via soy, in animal diets can alter morphology and physiology in rodents. Phytoestrogens have the ability to bind estrogen receptors and exert many of the biological responses evoked by physiological estrogens. This study characterized the effects of dietary phytoestrogens on the expression of body and prostate weight, circulating testosterone and estradiol levels, puberty onset, vaginal cyclicity, and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in Long-Evans rats. Using different experimental protocols, animals were fed either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet. Animals fed the Phyto-600 diet displayed significantly decreased body weights (in males and females), prostate weights and delayed puberty in females compared to that of animals fed the Phyto-free diet. Circulating testosterone or estradiol levels in males or estrous cyclicity were not altered by the diets. The volume of the SDN-POA was significantly altered by a change in diet at 80 days of age where one-half of the males or females fed the Phyto-600 diet (from birth) were switched to the Phyto-free diet until 120 days of age. Males initially fed a Phyto-600 diet but changed to a Phyto-free diet had significantly smaller SDN-POA volumes compared to males fed the Phyto-600 diet (long-term). These data suggest that consumption of phytoestrogens via a soy diet, significantly: (1) decreases body and prostate weight, (2) delays puberty onset, and (3) alters SDN-POA volumes during adulthood.

Topics: Aging; Animals; Atrophy; Body Weight; Cell Size; Estrogens; Estrogens, Non-Steroidal; Female; Food, Formulated; Genitalia; Glycine max; Isoflavones; Male; Neurons; Organ Size; Phytoestrogens; Plant Preparations; Preoptic Area; Prostate; Rats; Rats, Long-Evans; Reproduction; Sex Characteristics; Testosterone

Phytoestrogens are estrogen-like (plant-derived) molecules that protect against age-related diseases (cardiovascular disease and osteoporosis), hormone-dependent (breast and prostate) cancers and selectively bind estrogen receptors. However, little is known about the influence of phytoestrogens on brain. Using diets containing either high phytoestrogen levels, derived from soy, or very low phytoestrogens we quantified phytoestrogen concentrations of daidzein, genistein and equol in brain. We found that dietary phytoestrogens: significantly decrease body and prostate weights, do not alter brain aromatase levels and significantly change during adulthood the structure of the sexually dimorphic brain region (i.e. anteroventral periventricular nucleus; AVPV) in male, but not in female rats. Since most commercial animal diets contain significant concentrations of phytoestrogens their influence on brain structure should be considered.

Topics: Animals; Aromatase; Body Weight; Brain; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Isoflavones; Male; Organ Size; Phytoestrogens; Plant Preparations; Prostate; Rats; Rats, Long-Evans; Sex Factors

We investigated the ability of genistein and daidzein, two soybean isoflavones, compared with that of 17 alpha-ethinylestradiol, to prevent bone loss in ovariectomized rats, a model for postmenopausal osteoporosis. Female Wistar rats (n = 65; 12 mo old) were either sham-operated (SH; n = 13) or ovariectomized (OVX; n = 52). On d 0, OVX rats were randomly assigned to groups as follows: 13 received genistein [G; 10 mcg/(g body weight. d)], 13 were treated with daidzein [D; 10 mcg/(g body weight. d)], 13 received 17 alpha-ethinylestradiol [E(2); 30 mcg/kg body weight. d)] and 13 were untreated (OVX). Compounds were mixed with a soy protein-free powdered semipurified diet and given orally for 3 mo. On d 90, the bone mineral density (BMD) in lumbar vertebrae, femur and its metaphyseal and diaphyseal zones (rich in cancellous and cortical bone, respectively) was lower in OVX than in SH (P < 0.01). In D or E(2), the four BMD were not different from SH, whereas in G, only the diaphyseal BMD was not different from SH. Image analysis performed in the distal femur metaphysis revealed that the cancellous bone area was lower in OVX than in SH (P < 0.01). Only the area in D was not different from that in SH. Finally, the bone turnover, which was higher in OVX than in SH (P < 0.005 and P < 0.05 for plasma osteocalcin concentration and urinary deoxypyridinoline excretion, respectively), was not different in G, D or E(2) compared with SH. Therefore, consumption of 17 alpha-ethinylestradiol or daidzein was more efficient than genistein in preventing ovariectomy-induced bone loss in rats.

Topics: Animals; Body Weight; Bone Density; Equidae; Estrogens, Non-Steroidal; Female; Genistein; Goats; Humans; Isoflavones; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Preparations; Radioimmunoassay; Rats; Rats, Wistar

Ipriflavone (IP), a synthetic isoflavone, prevents bone loss associated with ovarian hormone deficiency in women and animal models. This protective effect of IP may be partly due to its ability to enhance calcium absorption. The purpose of this study was to examine the effects of IP and 17beta-estradiol (E(2)) on in vitro intestinal calcium transport in an ovariectomized rat model using E(2) as a positive control. Forty-eight 90-day-old female Sprague-Dawley rats were divided into four groups: one sham-operated (sham) and three ovariectomized groups. The ovx groups were either control (ovx), supplemented with IP (100 mg/kg body weight daily) via gavaging (ovx+IP), or injected with E(2) (10 microg/kg body weight) (ovx+E(2)). Animals were fed diets containing 0.4% calcium, 0.3% phosphorus, and 0.195 nmol vitamin D(3)/g for 35 days from the date of surgery. Animals were exsanguinated, and isolated cells from the duodenum, jejunum, ileum, and colon were used to measure in vitro calcium uptake. Calcium uptake by duodenal cells was significantly greater in the IP and E(2)-treated animals compared with the ovx control group. In addition, calcium uptake by the ileal and colonic cells of the E(2)-treated animals was significantly greater compared with all the other groups. The results confirm our earlier findings implicating a role for estrogen in duodenal calcium uptake. The findings also indicate that IP, although less potent than estrogen, significantly enhances calcium uptake in the duodenum, the active site of calcium absorption.

Topics: Administration, Oral; Animals; Biological Transport; Body Weight; Bone Remodeling; Calcium; Cell Separation; Creatinine; Eating; Estradiol; Estrogens, Non-Steroidal; Female; Intestinal Absorption; Intestinal Mucosa; Isoflavones; Organ Size; Ovariectomy; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; Uterus; Vitamin D

We report here the effects of oral micronized estradiol and soy phytoestrogens on uterine weight, choline acetyltransferase (ChAT) and nerve growth factor (NGF) mRNAs in the frontal cortex and hippocampus of ovariectomized young and retired breeder rats. Within each age category, 15 bilaterally ovariectomized rats were randomized equally into three groups: control (OVX), estradiol (E2), and soy phytoestrogens (SBE). The OVX rats were fed a casein/lactalbumin-based control diet; the E2 rats were fed with the control diet with added estradiol; and the SBE rats were fed with the control diet with added soy phytoestrogens. After 8 weeks of treatment, blood, uteri, frontal cortex, and hippocampus were collected at necropsy. Results showed that the uterine weights and serum estradiol concentrations were significantly higher in the E2 group compared with those in the OVX and SBE groups. In the hippocampus of young rats, E2 treatment resulted in significantly higher NGF mRNA levels than no treatment (OVX), and NGF mRNA levels in the SBE group were intermediate between the E2 and OVX groups. ChAT mRNA levels were significantly higher in the frontal cortex of E2 and SBE-treated retired breeder rats compared to OVX retired breeder rats. There were no differences among treatment groups for ChAT mRNA levels in the frontal cortex of young rats and in the hippocampus of both young and retired breeder rats. Our data suggest that soy phytoestrogens may function as estrogen agonists in regulating ChAT and NGF mRNAs in the brain of female rats.

Topics: Age Factors; Animals; Body Weight; Choline O-Acetyltransferase; Estradiol; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Frontal Lobe; Glycine max; Hippocampus; Isoflavones; Nerve Growth Factors; Organ Size; Ovariectomy; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley; RNA, Messenger; Uterus

The purpose of this study was to examine the short-term effects of phytoestrogens in the diet on regulatory behaviors (food/water intake and locomotor activity), prostate weight, testosterone levels, and brain androgen metabolizing enzyme activity levels in adult male rats. Sprague-Dawley rats were fed phytoestrogen-containing versus phytoestrogen-free diets for 29 days. Standard methods were used to measure open field behavior, reproductive, hormonal parameters, and enzymatic activity levels. The phytoestrogen diet contained approximately 200 microg/g of isoflavones whereas in the phytoestrogen-free diet, no phytoestrogens were detected by HPLC analysis. There were no significant differences in any of the regulatory behaviors (food/water intake or locomotor activity), prostate weight, or testosterone levels between the treatment groups. Furthermore, there was no significant influence of phytoestrogens on brain aromatase activity levels, in either the medial basal hypothalamic-preoptic area (MBH-POA) or amygdala brain tissue sites examined. However, significant alterations in MBH-POA and amygdala 5alpha-reductase activities were detected in animals receiving the phytoestrogen-containing versus the phytoestrogen-free diets.

Topics: Animals; Aromatase; Body Weight; Brain; Cholestenone 5 alpha-Reductase; Diet; Estrogens, Non-Steroidal; Feeding Behavior; Isoflavones; Male; Motor Activity; Organ Size; Oxidoreductases; Phytoestrogens; Plant Preparations; Prostate; Rats; Rats, Sprague-Dawley; Testosterone

The estrogenic actions of dietary phytoestrogens have raised concerns regarding the potential DES-like developmental effects on the female genital tract, but the growing evidence of cardioprotective benefits of dietary soybean estrogens provides the impetus to assess the effects of these compounds in adult female models of the menopause. We conducted an experiment in ovariectomized rats to determine the independent effects of dietary soybean estrogens (SBE) and the interactions of these agents with the commonly used pharmaceutical estrogen preparation (conjugated equine estrogens, CEE) in the vagina and uterus. We looked at the effects of SBE and CEE, alone and in combination, on uterine weight, body weight, vaginal cytology, uterine luminal epithelial height, and immunohistochemical staining for proliferating cell nuclear antigen (PCNA), lactoferrin (Ltf), and apoptosis. Ovariectomized rats were fed diets containing casein or soybean protein (SBE, low dose = 11.6 mg isoflavones/ 1800 cal; high dose = 117.8 mg/1800 cal), with no CEE, low dose CEE (0.313 mg/1800 cal), or high dose CEE (0.625 mg/1800 cal) added. In this study, SBE did not demonstrate estrogenic activity for uterine weight or vaginal cytology. We also found no estrogenic effects of these doses of SBE for PCNA, apoptosis, Ltf staining, or for LEH measurements. In addition, our results regarding the interactions of SBE and CEE do not show any evidence that the combination is additive in effect. On the contrary, the LEH response induced by low levels of CEE, was reduced by high levels of SBE. Furthermore, the Ltf response induced by CEE also was reduced by high levels of SBE. This suggests that high doses of SBE may antagonize the estrogen-agonist actions of low doses of CEE in the rat uterus. Our results in the ovariectomized rat model of menopause suggest that dietary soybean estrogens will not elicit a pattern of effects that simply recapitulates those of steroidal estrogens.

Topics: Animals; Apoptosis; Body Weight; Estrogens, Conjugated (USP); Estrogens, Non-Steroidal; Female; Genitalia, Female; Glycine max; Isoflavones; Ovariectomy; Phytoestrogens; Plant Preparations; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley

Soy protein, long recognized as having cardiovascular benefits, is a rich source of phytoestrogens (isoflavones). To distinguish the relative contributions of the protein moiety versus the alcohol-extractable phytoestrogens for cardiovascular protection, we studied young male cynomolgus macaques fed a moderately atherogenic diet and randomly assigned to three groups. The groups differed only in the source of dietary protein, which was either casein/lactalbumin (casein, n = 27), soy protein with the phytoestrogens intact (soy+, n = 27), or soy protein with the phytoestrogens mostly extracted (soy-, n = 28). The diets were fed for 14 months. Animals fed soy+ had significantly lower total and LDL plus VLDL cholesterol concentrations compared with the other two groups. They soy+ animals had the highest HDL cholesterol concentrations, the casein group had the lowest, and the soy- group was intermediate. A subset was necropsied for atherosclerosis evaluations (n = 11 per group). Morphometric and angiochemical measures were done to quantify atherosclerosis. Coronary artery atherosclerotic lesions were smallest in the soy+ group (90% less coronary atherosclerosis than the casein group and 50% less than the soy- group), largest in the casein group, and intermediate in the soy- group. The effects of the diets on lesion size and arterial lipid measures of the peripheral arteries were similar to those in the coronary arteries, with greatest prevention of atherogenesis with soy+ and intermediate benefit with soy- relative to casein. We could not determine whether the beneficial effects seen in the soy- group relate to the protein itself or to the remaining traces of phytoestrogens. The beneficial effects of soy protein on atherosclerosis appear to be mediated primarily by the phytoestrogen component. Testicular weights were unaffected by the phytoestrogens.

Topics: Animal Feed; Animals; Blood Vessels; Body Weight; Cholesterol Esters; Coronary Artery Disease; Diet, Atherogenic; Dietary Proteins; Estrogens, Non-Steroidal; Glycine max; Isoflavones; Lipids; Lipoproteins; Macaca fascicularis; Male; Milk Proteins; Organ Size; Phytoestrogens; Plant Preparations; Plant Proteins; Random Allocation; Testis; Testosterone

The effects of a phytoestrogen diet on sexual differentiation were examined in lactationally exposed rat pups. Rat dams were provided a semipurified diet containing the isoflavonoid coumestrol at a concentration (0.01%) previously found to be uterotrophic. Coumestrol treatment did not significantly alter the time of vaginal opening, although vaginal opening did occur at a lighter body weight. By 132 days of age, 83% of coumestrol-treated females exhibited the cornified smears of a persistent estrous state. By contrast, 91% of control animals were cycling regularly at 132 days of age. Estradiol stimulation failed to elicit an LH elevation in the coumestrol-treated animals, suggesting the possibility of neuroendocrine impairments. These findings indicate that the female offspring of mothers fed a low-level phytoestrogen diet during lactation manifest early and nearly universal disruption of cyclicity of the persistent-estrus type.

Topics: Animals; Anovulation; Body Weight; Coumestrol; Diet; Eating; Estrogens; Estrogens, Non-Steroidal; Female; Isoflavones; Lactation; Luteinizing Hormone; Phytoestrogens; Plant Preparations; Plants, Edible; Pregnancy; Rats; Rats, Sprague-Dawley; Sexual Maturation; Syndrome