RESUMO
Hippocampal neuropathology is a recognized feature of the spontaneously hypertensive rat (SHR). The hippocampal alterations associate with cognitive impairment. We have shown that hippocampal abnormalities are reversed by 17ß-estradiol, a steroid binding to intracellular receptors (estrogen receptor α and ß subtypes) or the membrane-located G-protein coupled estradiol receptor. Genistein (GEN) is a neuroprotective phytoestrogen which binds to estrogen receptor ß and G-protein coupled estradiol receptor. Here, we investigated whether GEN neuroprotection extends to SHR. For this purpose, we treated 5-month-old SHR for 2 weeks with 10 mg kg-1 daily s.c injections of GEN. We analyzed the expression of doublecortin+ neuronal progenitors, glial fibrillary acidic protein+ astrocytes and ionized calcium-binding adapter molecule 1+ microglia in the CA1 region and dentate gyrus of the hippocampus using immunocytochemistry, whereas a quantitative real-time polymerase chain reaction was used to measure the expression of pro- and anti-inflammatory factors tumor necrosis factor α, cyclooxygenase-2 and transforming growth factor ß. We also evaluated hippocampal dependent memory using the novel object recognition test. The results showed a decreased number of doublecortin+ neural progenitors in the dentate gyrus of SHR that was reversed with GEN. The number of glial fibrillary acidic protein+ astrocytes in the dentate gyrus and CA1 was increased in SHR but significantly decreased by GEN treatment. Additionally, GEN shifted microglial morphology from the predominantly activated phenotype present in SHR, to the more surveillance phenotype found in normotensive rats. Furthermore, treatment with GEN decreased the mRNA of the pro-inflammatory factors tumor necrosis factor α and cyclooxygenase-2 and increased the mRNA of the anti-inflammatory factor transforming growth factor ß. Discrimination index in the novel object recognition test was decreased in SHR and treatment with GEN increased this parameter. Our results indicate important neuroprotective effects of GEN at the neurochemical and behavioral level in SHR. Our data open an interesting possibility for proposing this phytoestrogen as an alternative therapy in hypertensive encephalopathy.
Assuntos
Genisteína , Fitoestrógenos , Ratos , Animais , Ratos Endogâmicos SHR , Genisteína/farmacologia , Fitoestrógenos/farmacologia , Fitoestrógenos/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Receptores de Estradiol/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ratos Endogâmicos WKY , Hipocampo/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas do Domínio Duplacortina , RNA Mensageiro/metabolismoRESUMO
The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.
Assuntos
Anticoncepcionais Orais/metabolismo , Hormônios/metabolismo , Imunomodulação , Fígado/imunologia , Fígado/metabolismo , Fitoestrógenos/metabolismo , Anticoncepcionais Orais/farmacologia , Feminino , Hormônios/farmacologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunomodulação/efeitos dos fármacos , Fígado/efeitos dos fármacos , Estrutura Molecular , Fitoestrógenos/farmacologia , Fatores SexuaisRESUMO
Breast cancer is a highly heterogeneous disease influenced by the hormonal microenvironment and the most common malignancy in women worldwide. Some phytoestrogens and mycoestrogens have been epidemiologically linked as risk factors or protectors, however their mechanisms of action are complex and not fully understood. The aim of this study was to predict the potential of 36 natural xenoestrogens to interact with 189 breast cancer proteins using AutoDock Vina. In order to validate our protocol, an in silico docking pose and binding site determination was compared with the crystallographic structure and the power of prediction to distinguish between ligand and decoys was evaluated through a receiver operating characteristic curve (ROC) of the resultant docking affinities and in vitro data. The best affinity score was obtained for glyceollin III interacting with the sex hormone binding globulin (-11.9 Kcal/mol), a plasma steroid transport protein that regulates sex steroids bioavailability. Other natural xenoestrogens such as beta-carotene, chrysophanol 8-O-beta-d-glucopyranoside and glyceollin I, also presented good affinity for proteins related to this disease and the validation was successful. This study may help to prioritize compounds for toxicity tests or drug development from natural scaffolds, and to elucidate their mechanisms of action.
Assuntos
Neoplasias da Mama , Disruptores Endócrinos/metabolismo , Fungos , Proteínas de Neoplasias/metabolismo , Fitoestrógenos/metabolismo , Simulação por Computador , Disruptores Endócrinos/farmacologia , Simulação de Acoplamento Molecular , Proteínas de Neoplasias/química , Fitoestrógenos/farmacologia , Ligação Proteica , Conformação ProteicaRESUMO
Phytoestrogens are of interest because of their reported beneficial effects on many human maladies including cancer, neurodegeneration, cardiovascular disease and diabetes. Furthermore, there is a search for compounds with estrogenic activity that can replace estrogen in hormone replacement therapy during menopause, without the undesirable effects of estrogen, such as the elevation of breast cancer occurrence. Thus, the principal objective of this study was to assess the estrogenic activity of flavonoids with different hydroxylation patterns: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3-hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone via two different in vitro assays, the recombinant yeast assay (RYA) and the MCF-7 proliferation assay (E-screen), since the most potent phytoestrogens are members of the flavonoid family. In these assays, kaempferol was the only compound that showed ERα-dependent transcriptional activation activity by RYA, showing 6.74±1.7 nM EEQ, besides acting as a full agonist for the stimulation of proliferation of MCF-7/BUS cells. The other compounds did not show detectable levels of interaction with ER under the conditions used in the RYA. However, in the E-screen assay, compounds such as galangin, luteolin and fisetin also stimulated the proliferation of MCF-7/BUS cells, acting as partial agonists. In the evaluation of antiestrogenicity, the compounds quercetin, chrysin and 3-hydroxyflavone significantly inhibited the cell proliferation induced by 17-ß-estradiol in the E-screen assay, indicating that these compounds may act as estrogen receptor antagonists. Overall, it became clear in the assay results that the estrogenic activity of flavonoids was affected by small structural differences such as the number of hydroxyl groups, especially those on the B ring of the flavonoid.
Assuntos
DNA Recombinante/genética , Flavonoides/farmacologia , Fitoestrógenos/farmacologia , Leveduras/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/metabolismo , Humanos , Hidroxilação , Células MCF-7 , Fitoestrógenos/metabolismo , Leveduras/citologiaRESUMO
Adhesion activity of L. acidophilus NK1, L. fermentum 90 TS4, and C. albicans 506 B on female vaginal epithelium was studied. Adhesion of various lactobacillus species was hormone-dependent. Adhesion of C. albicans 506 B was not associated with estrogen level. The effects of synthetic drugs and phytopreparations used for hormone replacement on adhesion of vaginal microbiocenosis members varied.
Assuntos
Lactobacillus/fisiologia , Vagina/microbiologia , Adolescente , Adulto , Aderência Bacteriana/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Combinação de Medicamentos , Epitélio/microbiologia , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Humanos , Lactobacillus/efeitos dos fármacos , Levanogestrel/farmacologia , Pessoa de Meia-Idade , Fitoestrógenos/metabolismo , Fitoestrógenos/farmacologia , Vagina/metabolismo , Adulto JovemRESUMO
Breast cancer (BC) is a polygenic and multifactorial disease for which estrogens have been recognized as the main risk factor, and for which lifestyle plays a key role. Previous epidemiologic cancer research performed in Uruguayan population delimited its dietary and anthropometric profiles. Recognizing the difficulty for universalizing a nutritional basis for prevention due to different eating patterns among regions and countries, we summarize the existent knowledge linking nutrition, estrogens, metabolism and BC. As an attempt towards primary prevention of BC, we present recommendations mainly based on country-specific research findings and modifiable putative risk and protective factors, proposing to modify the intake of meats and other fatty foods--especially sources of Ω-6 and Ω-3 fatty acids--adding olive oil, selected vegetables, citrus fruits and working towards adequate body fat/muscle proportions. From a medical and ethical viewpoint, it is justified to recommend certain nutritional changes to women, because no adverse side effects are expected to occur.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/prevenção & controle , Estrogênios/metabolismo , Comportamento Alimentar , Alimentos , Antropometria , Neoplasias da Mama/epidemiologia , Carotenoides/metabolismo , Colesterol/metabolismo , Dieta , Gorduras na Dieta/efeitos adversos , Estrogênios/efeitos adversos , Feminino , Humanos , Carne , Fitoestrógenos/metabolismo , Prevenção Primária , Fatores de Risco , Uruguai/epidemiologia , Verduras , Vitamina D/metabolismoRESUMO
Embora a soja em grão seja pouco consumida pela população brasileira, seus derivados protéicos são utilizados como ingredientes em diversos alimentos e a tendência é um aumento significativo do seu uso com a aprovação pela FDA e pela ANVISA da alegação funcional referente ao consumo de proteína de soja. Em paralelo, um número crescente de pesquisas sobre as isoflavonas, fitoestrógenos presentes em quantidades significativas na soja, vem demonstrando diversos efeitos benéficos destes compostos, entre os quais a sua ação antioxidante, anticarcinogênica e hipocolesterolêmica. O objetivo foi estudar as interações entre isoflavonas e proteínas da soja, seu efeito na biodisponibilidade in vitro e in vivo e o status antioxidante das isoflavonas. Os resultados sugerem que a presença da proteína reduz a quantidade e leva a um retardo no tempo de absorção das isoflavonas em relação à administração na forma livre. O efeito sobre a capacidade antioxidante do plasma e sobre a atividade e expressão gênica das enzimas CAT, GPx e SOD divergiu para a suplementação de isoflavonas ou proteínas separadamente ou em associação...