RESUMO
High adipose tissue (AT) accumulation in the body increases the risk for many metabolic and chronic diseases. This work investigated the capacity of the flavonoid (-)-epicatechin to prevent undesirable modifications of AT in mice fed a high-fat diet. Studies were focused on thoracic aorta perivascular AT (taPVAT), which is involved in the control of blood vessel tone, among other functions. Male C57BL/6J mice were fed for 15 weeks a high-fat diet with or without added (-)-epicatechin (20 mg per kg body weight per d). In high-fat diet fed mice, (-)-epicatechin supplementation: (i) prevented the expansion of taPVAT, (ii) attenuated the whitening of taPVAT (according to the adipocyte morphology, diameter, and uncoupling-protein 1 (UCP-1) levels) and (iii) blunted the increase in plasma glucose and cholesterol. The observed taPVAT modifications were not associated with alterations in the aorta wall thickness, aorta tumor necrosis factor-alpha (TNF-α) and NADPH-oxidase 2 (NOX2) expression, and endothelial nitric oxide synthase (eNOS) phosphorylation levels. In summary, our results indicate (-)-epicatechin as a relevant bioactive protecting from the slow and silent development of metabolic and chronic diseases as they are associated with excessive fat intake.
Assuntos
Tecido Adiposo/patologia , Aorta Torácica/patologia , Catequina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Suplementos Nutricionais , Extratos Vegetais/farmacologia , Adipócitos/metabolismo , Adipócitos/patologia , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Tecido Adiposo Branco , Animais , Aorta Torácica/metabolismo , Glicemia/metabolismo , Catequina/uso terapêutico , Colesterol/sangue , Gorduras na Dieta/administração & dosagem , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Doenças Metabólicas/prevenção & controle , Camundongos Endogâmicos C57BL , NADPH Oxidase 2/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/metabolismo , Obesidade/prevenção & controle , Extratos Vegetais/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Proteína Desacopladora 1/metabolismoRESUMO
This study investigated the effects of a quercetin-supplemented diet on the biochemical changes installed in the heart of NO-deficient rats in terms of oxidants production and NO bioavailability determinants. Sprague-Dawley rats were subjected to Nω-nitro-l-arginine methyl ester (l-NAME) treatment (360â¯mg/L l-NAME in the drinking water, 4â¯d) with or without supplementation with quercetin (4â¯g/kg diet). l-NAME administration led to increased blood pressure (BP) (30%), decreased nitric oxide synthase (NOS) activity (50%), and increases in NADPH oxidase (NOX)-dependent superoxide anion production (60%) and p47phox protein level (65%). The co-administration of quercetin prevented the increase in BP and the activation of NOX but did not modify the decrease in NOS activity caused by l-NAME. In addition, quercetin affected oxidative stress parameters as glutathione oxidation, and the activities of oxidant detoxifying enzymes superoxide dismutase, glutathione peroxidase, and catalase. Thus, quercetin administration counteracts l-NAME effects on NO bioavailability determinants in vivo, essentially through controlling NOX-mediated superoxide anion production.
Assuntos
Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Quercetina/farmacologia , Animais , Antioxidantes/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Glutationa/metabolismo , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Hipertensão/prevenção & controle , Masculino , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Quercetina/administração & dosagem , Ratos Sprague-Dawley , Superóxidos/metabolismoRESUMO
This work investigated the blood pressure (BP)-lowering effect of the flavanol (-)-epicatechin in a model of metabolic syndrome. Rats were fed a regular chow diet without (Control) or with 10% (w/v) fructose in the drinking water (high fructose, HF) for 8 weeks. A subgroup of the HF-fed rats was supplemented with (-)-epicatechin 20 mg/kg body weight (HF-EC). Dietary (-)-epicatechin reverted the increase in BP caused by the fructose treatment. In aorta, superoxide anion production and the expression of the NADPH oxidase (NOX) subunits p47(phox) and p22(phox) were enhanced in the HF-fed rats. The increase was prevented by (-)-epicatechin. Similar profile was observed for NOX4 expression. The activity of aorta nitric oxide synthase (NOS) was increased in the HF group and was even higher in the HF-EC rats. These effects were paralleled by increased endothelial NOS phosphorylation at the activation site Ser1177. Among the more relevant mitogen-activated protein kinase pathways in vascular tissue, c-Jun-N-terminal kinase was shown to be activated in the aorta of the HF-fed rats, and (-)-epicatechin supplementation mitigated this activation. Thus, the results suggest that dietary (-)-epicatechin supplementation prevented hypertension in HF-fed rats, decreasing superoxide anion production and elevating NOS activity, favoring an increase in NO bioavailability.
Assuntos
Anti-Hipertensivos/uso terapêutico , Catequina/uso terapêutico , Suplementos Nutricionais , Endotélio Vascular/enzimologia , Hipertensão/prevenção & controle , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/agonistas , Animais , Antioxidantes/uso terapêutico , Aorta Torácica/enzimologia , Aorta Torácica/metabolismo , Aorta Torácica/patologia , Carboidratos da Dieta/efeitos adversos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Frutose/efeitos adversos , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/patologia , Sistema de Sinalização das MAP Quinases , Masculino , NADPH Oxidase 4 , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/química , Fosforilação , Processamento de Proteína Pós-Traducional , Distribuição Aleatória , Ratos Sprague-Dawley , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismoRESUMO
Epidemiological and intervention studies have shown that the intake of certain chocolates or cocoa products decreases blood pressure (BP) in humans. (-)-Epicatechin is the most abundant flavanol present in cocoa seeds and its derived foods. This work investigates the effects of dietary (-)-epicatechin on BP in rats that received N(ω)-nitro-l-arginine methyl ester (L-NAME) for 4 days. (-)-Epicatechin administration prevented the 42mm Hg increase in BP associated with the inhibition of NO production in a dose-dependent manner (0.2-4.0g/kg diet). This BP effect was associated with a reduction in L-NAME-mediated increase in the indexes of oxidative stress (plasma TBARS and GSSG/GSH(2) ratio) and with a restoration of the NO concentration. At the vascular level, none of the treatments modified NOS expression, but (-)-epicatechin administration avoided the L-NAME-mediated decrease in eNOS activity and increase in both superoxide anion production and NOX subunit p47(phox) expression. In summary, (-)-epicatechin was able to prevent the increase in BP and in oxidative stress and restored NO bioavailability. The fact that (-)-epicatechin is present in several plants usually consumed by humans gives the possibility of developing diets rich in those plants or pharmacological strategies using that flavonoid to diminish BP in hypertensive subjects.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Catequina/farmacologia , Hipertensão/tratamento farmacológico , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Animais , Pressão Sanguínea/fisiologia , Suplementos Nutricionais , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Masculino , Óxido Nítrico Sintase/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacosRESUMO
Increasing evidence indicates that several mechanisms, associated or not with antioxidant actions, are involved in the effects of flavonoids on health. Flavonoid-rich beverages, foods, and extracts, as well as pure flavonoids are studied for the prevention and/or amelioration of metabolic syndrome (MS) and MS-associated diseases. We summarize evidence linking flavonoid consumption with the risk factors defining MS: obesity, hypertriglyceridemia, hypercholesterolemia, hypertension, and insulin resistance. Nevertheless, a number of molecular mechanisms have been identified; the effects of flavonoids modifying major endpoints of MS are still inconclusive. These difficulties are explained by the complex relationships among the risk factors defining MS, the multiple biological targets controlling these risk factors, and the high number of flavonoids (including their metabolites) present in the diet and potentially responsible for the in vivo effects. Consequently, extensive basic and clinical research is warranted to assess the final relevance of flavonoids for MS.
Assuntos
Flavonoides/farmacologia , Flavonoides/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Animais , Dieta , Humanos , Inflamação/dietoterapia , Inflamação/etiologia , Inflamação/prevenção & controle , Síndrome Metabólica/etiologia , Modelos Biológicos , Obesidade/dietoterapia , Obesidade/etiologia , Obesidade/prevenção & controle , Fitoterapia/métodosRESUMO
Diets rich in fruits and vegetables have been associated with benefits for human health. Those effects have been partially ascribed to their content in flavonoids, compounds that are present in many edible plants and its derived foods. In humans, a significant number of studies has been developed analyzing the effect of foods and beverages rich in flavonoids on the presence and progression of risk factors associated to cardiovascular diseases, including hypertension. Cocoa derived products, rich in flavanols, have been thoroughly studied and demonstrated to be efficient improving endothelial function and decreasing blood pressure in humans and animals. However, the final chemical species and the mechanism/s responsible for these effects have not been completely defined. In this paper we present data supporting the hypothesis that flavanols could define superoxide anion production and then, establish optimal nitric oxide levels and blood pressure.