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OBJECTIVES: To investigate the effects of a Brazil nut-enriched diet on the wall thickness and the left ventricular chamber diameter of the heart, and lipid peroxidation in a CKD-induced model. METHODS: Male Wistar rats at 12 weeks of age were divided into two groups (n=16/group): the Nx group, which underwent 5/6 nephrectomy, and the Sham group, as a control. After 5 weeks, the groups were subdivided according to diet (n=8/group): the Nx and Sham groups received a control diet; the Nx5% and Sham5% groups received a diet enriched with 5â¯% Brazil nuts for 8 weeks. The left ventricular thickening and chamber diameter were determined. Plasma biochemical parameters were evaluated. Analysis of thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity was performed in the plasma and the left ventricle (LV). LV mRNA expression of nuclear factor-kappa B (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated by reverse transcription-polymerase chain reaction. RESULTS: The Nx5% group showed a remodeled LV wall with decreased thickness compared to the Nx group (p=0.016). Furthermore, LV TBARS concentration was reduced in the Nx5% group (p=0.0064). In addition, the Nx5% group showed an increase in plasma GPx activity (p=0.0431). No significant results were found concerning the LV mRNA expression of NF-κB and Nrf2 genes. CONCLUSIONS: A Brazil nut-enriched diet decreased LV thickness and LV TBARS concentration and increased GPx activity in a 5/6 nephrectomy experimental model, making it a promising adjuvant therapy to improve antioxidant status and cardiovascular outcomes in chronic kidney disease.
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Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals.
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Adiposidade , Catalase , Gordura Intra-Abdominal , Peroxidação de Lipídeos , Oxirredução , Estresse Oxidativo , Ratos Wistar , Compostos de Trialquitina , Animais , Masculino , Compostos de Trialquitina/toxicidade , Oxirredução/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Adiposidade/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Catalase/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Glutationa Peroxidase/metabolismoRESUMO
Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 µg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFß, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation.
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Cardiomegalia , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Fenóis , Animais , Masculino , Dieta Hiperlipídica/efeitos adversos , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Camundongos , Fenóis/toxicidade , Remodelação Ventricular/efeitos dos fármacos , SulfonasRESUMO
OBJECTIVE: This study investigates the effects of a Brazil nut-enriched diet on body composition and bone parameters in CKD animal model. METHODS: Male Wistar rats were assigned to the following groups: Sham (n=8), Nx (n=6), nephrectomized rats, and NxBN (n=6), nephrectomized rats and an enricheddiet with 5% Brazil nut. Body composition parameters were obtained by dual-energy X- ray absorptiometry (DXA). Bioclin kits determined plasmatic calcium. The femurs werecollected to determine absolute mass and length, bone mineral density, and biomechanical tests. RESULTS: The NxBN group exhibited a higher total body bone mineral density (BMD) value than the Nx group (0.177±0.004g/cm2vs 0,169±0.003g/cm2; p=0.0397). No significant differences were observed regarding absolute mass, length, BMD, and biomechanical parameters in the femurs of the groups. Moreover, no significant differences were found in plasmatic calcium levels among the groups. CONCLUSIONS: Brazil-nut enriched diet modulated BMD in CKD experimental model, and further studies are demanded to understand the pathways involved in this finding.
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Bertholletia , Composição Corporal , Densidade Óssea , Dieta , Modelos Animais de Doenças , Fêmur , Ratos Wistar , Insuficiência Renal Crônica , Animais , Masculino , Insuficiência Renal Crônica/dietoterapia , Insuficiência Renal Crônica/fisiopatologia , Ratos , Dieta/métodos , Fêmur/fisiopatologia , Absorciometria de Fóton , Cálcio/sangue , NozesRESUMO
AIM: Evidence suggests that translocation of oral pathogens through the oral-gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice. METHODS: Eight-week-old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non-parametric tests. RESULTS: The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2-infected mice than in controls (p < .05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL-6 expression in colonic tissues, and higher splenic MPO activity than controls (p < .05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL-6 levels than controls (p < .05). CONCLUSION: Based on this model, intragastric administration of Aa JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro-inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.
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The renin-angiotensin system (RAS) is an endocrine system composed of two main axes: the classical and the counterregulatory, very often displaying opposing effects. The classical axis, primarily mediated by angiotensin receptors type 1 (AT1R), is linked to obesity-associated metabolic effects. On the other hand, the counterregulatory axis appears to exert antiobesity effects through the activation of two receptors, the G protein-coupled receptor (MasR) and Mas-related receptor type D (MrgD). The local RAS in adipose organ has prompted extensive research into white adipose tissue and brown adipose tissue (BAT), with a key role in regulating the cellular and metabolic plasticity of these tissues. The MasR activation favors the brown plasticity signature in the adipose organ by improve the thermogenesis, adipogenesis, and lipolysis, decrease the inflammatory state, and overall energy homeostasis. The MrgD metabolic effects are related to the maintenance of BAT functionality, but the signaling remains unexplored. This review provides a summary of RAS counterregulatory actions triggered by Mas and MrgD receptors on adipose tissue plasticity. Focus on the effects related to the morphology and function of adipose tissue, especially from animal studies, will be given targeting new avenues for treatment of obesity-associated metabolic effects.
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Tecido Adiposo , Proto-Oncogene Mas , Receptores Acoplados a Proteínas G , Sistema Renina-Angiotensina , Animais , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Obesidade/metabolismo , Obesidade/patologia , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina/fisiologia , Transdução de SinaisRESUMO
Obesity over-activates the classical arm of the renin-angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin-converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high-fat (HF) diet for 16 weeks. At the eighth week, the HF-fed animals were divided into four subgroups-sedentary (HF), treated with enalapril (HF-E), exercise training protocol (HF-T), and combined interventions (HF-ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF-T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity-induced muscle remodeling. Additionally, the use of enalapril impaired muscle's physiological adaptations to exercise training.
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Inibidores da Enzima Conversora de Angiotensina , Enalapril , Camundongos Endogâmicos C57BL , Músculo Esquelético , Obesidade , Condicionamento Físico Animal , Animais , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/fisiopatologia , Condicionamento Físico Animal/fisiologia , Camundongos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Enalapril/farmacologia , Dieta Hiperlipídica/efeitos adversos , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologiaRESUMO
Overactivation of the classic arm of the renin-angiotensin system (RAS) is one of the main mechanisms involved in obesity-related cardiac remodeling, and a possible relationship between RAS and ER stress in the cardiovascular system have been described. Thus, the aim of this study is to evaluate if activating the protective arm of the RAS by ACE inhibition or aerobic exercise training could overturn diet-induced pathological cardiac hypertrophy by attenuating ER stress. Male C57BL/6 mice were fed a control (SC) or a high-fat diet (HF) for 16 weeks. In the 8th week, HF-fed animals were randomly divided into HF, enalapril treatment (HF-En), and aerobic exercise training (HF-Ex) groups. Body mass (BM), food and energy intake, plasma analyzes, systolic blood pressure (SBP), physical conditioning, and plasma ACE and ACE2 activity were evaluated. Cardiac morphology, and protein expression of hypertrophy, cardiac metabolism, RAS, and ER stress markers were assessed. Data presented as mean ± standard deviation and analyzed by one-way ANOVA with Holm-Sidak post-hoc. HF group had increased BM and SBP, and developed pathological concentric cardiac hypertrophy, with overactivation of the classic arm of the RAS, and higher ER stress. Both interventions reverted the increase in BM, and SBP, and favored the protective arm of the RAS. Enalapril treatment improved pathological cardiac hypertrophy with partial reversal of the concentric pattern, and slightly attenuated cardiac ER stress. In contrast, aerobic exercise training induced physiological eccentric cardiac hypertrophy, and fully diminished ER stress.
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Cardiomegalia , Enalapril , Estresse do Retículo Endoplasmático , Obesidade , Condicionamento Físico Animal , Animais , Masculino , Enzima de Conversão de Angiotensina 2/sangue , Cardiomegalia/etiologia , Cardiomegalia/terapia , Enalapril/farmacologia , Enalapril/uso terapêutico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Camundongos Endogâmicos C57BL , Obesidade/complicações , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Transdução de Sinais/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêuticoRESUMO
Introduction: Chronic kidney disease (CKD) promotes gut dysbiosis, and enteric glial reactivity, a feature of intestinal inflammation. Brazil nut modulated enteric glial profile in healthy animals and could modulate these cells in 5/6 nephrectomized rats.Methods: A 5/6 nephrectomy-induced CKD and Sham-operated rats were divided as follows: CKD and Sham received a standard diet and CKD-BN and Sham-BN received a 5% Brazil nut enriched-diet. The protein content of glial fibrillary acid protein (GFAP), enteric glial marker, and GPx protein content and activity were assessed in the colon. The major phyla of gut microbiota were assessed.Results: CKD-BN group presented a decrease in GFAP content (p = 0.0001). The CKD-BN group modulated the abundance of Firmicutes, increasing its proportion compared to the CKD group. The CKD-BN group showed increased GPx activity in the colon (p = 0.0192), despite no significant difference in protein content.Conclusion: Brazil nut-enriched diet consumption decreased enteric glial reactivity and modulated gut microbiota in the CKD experimental model.
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Bertholletia , Microbioma Gastrointestinal , Insuficiência Renal Crônica , Ratos , Animais , Dieta , Neuroglia/metabolismo , Insuficiência Renal Crônica/metabolismoRESUMO
Dairy foods have become an interest in chronic kidney disease (CKD) due to their nutritional profile, which makes them a good substrate for probiotics incorporation. This study evaluated the effect of probiotic-enriched Minas cheese with Lactobacillus acidophilus La-05 in an experimental rat model for CKD on cardiac, inflammatory, and oxidative stress parameters. Male Wistar rats were divided into 4 groups (n = 7/group): 5/6 nephrectomy + conventional Minas cheese (NxC); 5/6 nephrectomy + probiotic Minas cheese (NxPC); Sham + conventional Minas cheese (ShamC); Sham + probiotic Minas cheese (ShamPC). Offering 20 g/day of Minas cheese with Lact. acidophilus La-05 (108-109 log CFU/g) for 6 weeks. The cardiomyocyte diameter was determined. Superoxide dismutase (SOD) activity in plasma, heart, kidney, and colon tissue was performed. At the end of supplementation, no significant changes in lipid profile and renal parameters were found. The NxPC group showed a decrease in cardiomyocyte diameter compared to the NxC group (16.99 ± 0.85 vs. 19.05 ± 0.56 µm, p = 0.0162); also they showed reduced plasmatic SOD activity (502.8 ± 49.12 vs. 599.4 ± 94.69 U/mL, p < 0.0001). In summary, probiotic-enriched Minas cheese (Lact. acidophilus La-05) consumption suggests a promisor cardioprotective effect and was able to downregulate SOD activity in a rat model of CKD.
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Parabens are classified as endocrine-disrupting chemicals (EDCs) capable of interfering with the normal functioning of the thyroid, affecting the proper regulation of the biosynthesis of thyroid hormones (THs), which is controlled by the hypothalamic-pituitary-thyroid axis (HPT). Given the crucial role of these hormones in health and the growing evidence of diseases related to thyroid dysfunction, this review looks at the effects of paraben exposure on the thyroid. In this study, we considered research carried out in vitro and in vivo and epidemiological studies published between 1951 and 2023, which demonstrated an association between exposure to parabens and dysfunctions of the HPT axis. In humans, exposure to parabens increases thyroid-stimulating hormone (TSH) levels, while exposure decreases TSH levels in rodents. The effects on THs levels are also poorly described, as well as peripheral metabolism. Regardless, recent studies have shown different actions between different subtypes of parabens on the HPT axis, which allows us to speculate that the mechanism of action of these parabens is different. Furthermore, studies of exposure to parabens are more evident in women than in men. Therefore, future studies are needed to clarify the effects of exposure to parabens and their mechanisms of action on this axis.
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Parabenos , Glândula Tireoide , Masculino , Humanos , Feminino , Glândula Tireoide/metabolismo , Parabenos/toxicidade , Hormônios Tireóideos/metabolismo , Hormônios/metabolismo , Tireotropina/metabolismoAssuntos
Anatomia , Coração , Humanos , Imageamento Tridimensional , Impressão Tridimensional , Anatomia/educaçãoRESUMO
Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects million women worldwide, presenting a complex pathophysiology that has not been fully elucidated yet. Recently, it has been suggested that PCOS triggers the endoplasmic reticulum (ER) stress, thus being associated with unfolded protein response (UPR) activation. Indeed, the UPR response has been associated with several pathological conditions, including in the reproductive system. Several studies demonstrated that ovarian UPR markers are upregulated in PCOS, being associated with worst ovarian outcomes, and this was ameliorated by ER stress inhibition. In this review, we aim to summarize the main findings from previous studies covering this topic, in an attempt to clarify the potential role of ER stress and the UPR response in the pathophysiology of PCOS.
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Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Resposta a Proteínas não DobradasRESUMO
AIMS: Endoplasmic reticulum (ER) stress poses a new pathological mechanism for metabolic-associated fatty liver disease (MAFLD). MAFLD treatment has encompassed renin-angiotensin system (RAS) blockers and aerobic exercise training, but their association with hepatic ER stress is not well known. Therefore, we aimed to compare the effects of hepatic RAS modulation by enalapril and/or aerobic exercise training over ER stress in MAFLD caused by a diet-induced obesity model. MAIN METHODS: C57BL/6 mice were fed a standard-chow (CON, n = 10) or a high-fat (HF, n = 40) diet for 8 weeks. HF group was then randomly divided into: HF (n = 10), HF + Enalapril (EN, n = 10), HF + Aerobic exercise training (AET, n = 10), and HF + Enalapril+Aerobic exercise training (EN + AET, n = 10) for 8 more weeks. Body mass (BM) and glucose profile were evaluated. In the liver, ACE and ACE2 activity, morphology, lipid profile, and protein expression of ER stress and metabolic markers were assessed. KEY FINDINGS: Both enalapril and aerobic exercise training provided comparable efficacy in improving diet-induced MAFLD through modulation of RAS and ER stress, but the latter was more efficient in improving ER stress, liver damage and metabolism. SIGNIFICANCE: This is the first study to evaluate pharmacological (enalapril) and non-pharmacological (aerobic exercise training) RAS modulators associated with ER stress in a diet-induced MAFLD model.
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Enalapril , Estresse do Retículo Endoplasmático , Animais , Camundongos , Biomarcadores/metabolismo , Dieta , Enalapril/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Oxidative stress, adipose tissue, and bone compartments can be disturbed in chronic diseases. Non-pharmacological strategies, such as Brazil nuts (BNs), can improve these parameters. This study evaluated the effects of BN supplementation at different concentrations on body composition, lipid profile, and peroxidation in healthy rats. Male Wistar rats were divided into three groups: control (CT), Brazil nut 5% (BN5), and Brazil nut 10% (BN10) groups. Body composition, brown adipose tissue (BAT), plasma lipid peroxidation, and lipid profile were evaluated in the three groups. The BN5 group showed an improvement in all bone parameters compared with that of the CT group (p < .0001). The BN5 and BN10 groups showed reduced plasma lipid peroxidation compared with that of the CT group (p = .0009), whereas the BN10 group presented lower BAT lipid peroxidation than that of the other groups (p = .01). High-density lipoprotein-cholesterol (HDL-c) levels were higher in the BN5 group than in the CT group (p = .01). Conclusively, the use of BNs in a controlled manner promoted improvement in bone parameters, HDL-c levels, and lipid peroxidation in healthy rats. PRACTICAL APPLICATIONS: Nuts has been included in the diet because of their versatility, acceptance, and easy access. Among them, Brazil nut (BN) is considered one of the major known food sources of selenium as well as a source of fibers, unsaturated fatty acids, and phenolic compounds. Studies have shown that BN supplementation is effective in reducing oxidative stress, inflammation, lipid peroxidation, and selenium deficiency when used as a non-pharmacological strategy in experimental models of chronic diseases and in clinical trials. The present study showed that controlled administration of BN improved bone parameters, high-density lipoprotein-cholesterol levels, and lipid peroxidation in healthy rats. Therefore, BN is a promising non-pharmacological agent for the prevention of the onset of chronic non-communicable diseases.
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Bertholletia , Selênio , Animais , Masculino , Ratos , Composição Corporal , Colesterol , Dieta , Suplementos Nutricionais , Ácidos Graxos Insaturados , Peroxidação de Lipídeos , Lipídeos , Lipoproteínas HDL , Ratos WistarRESUMO
INTRODUCTION: Obesity-related metabolic diseases occur as a result of disruptions in white adipose tissue (WAT) plasticity, especially through visceral fat accumulation and adipocyte hypertrophy. This study aimed to evaluate the impact of renin-angiotensin system (RAS) and bradykinin receptors modulation by enalapril treatment and/or exercise training on WAT morphology and related deleterious outcomes. METHODS: Male C57BL/6 mice were fed either a standard chow or a high-fat (HF) diet for 16 weeks. At the 8th week, HF-fed animals were divided into sedentary (HF), enalapril treatment (HF-E), exercise training (HF-T), and enalapril treatment plus exercise training (HF-ET) groups. Following the experimental protocol, body mass gain, adiposity index, insulin resistance, visceral WAT morphometry, renin-angiotensin system, and bradykinin receptors were evaluated. RESULTS: The HF group displayed increased adiposity, larger visceral fat mass, and adipocyte hypertrophy, which was accompanied by insulin resistance, overactivation of Ang II/AT1R arm, and favoring of B1R in bradykinin receptors profile. All interventions ameliorated visceral adiposity and related outcomes by favoring the Ang 1-7/MasR arm and the B2R expression in B1R/B2R ratio. However, combined therapy additively reduced Ang II/Ang 1-7 ratio. CONCLUSION: Our results suggest that Ang 1-7/MasR arm and B2R activation might be relevant targets in the treatment of visceral obesity.
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Enalapril/farmacologia , Condicionamento Físico Animal/fisiologia , Sistema Renina-Angiotensina/fisiologia , Tecido Adiposo Branco/metabolismo , Adiposidade/efeitos dos fármacos , Adiposidade/fisiologia , Animais , Dieta Hiperlipídica , Enalapril/metabolismo , Insulina/metabolismo , Resistência à Insulina/fisiologia , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade Abdominal/metabolismo , Receptores da Bradicinina/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacosRESUMO
Introdution: Endothelium integrity is a key that maintains vascular homeostasis but it can suffer irreversible damage by blood pressure changes, reflecting an imbalance in the maintenance of vascular homeostasis.Objective: The aim of this study was to investigate the impact of Brazil nut (Bertholletia excelsa, H.B.K.) (BN) supplementation (10% in chow, wt/wt) on the vascular reactivity of Wistar rats during chronic exposure to a sodium overload (1% in water).Methods: First, male Wistar rats were allocated into two groups: Control Group (CG) and the Hypersodic Group (HG) for 4 weeks. Afterward, the CG was divided into the Brazil Nut Group (BNG) and the HG Group into the Hypersodic Brazil Nut Group (HBNG) for a further 8 weeks, totaling 4 groups. Blood pressure was measured during the protocol. At the end of the protocol, the vascular reactivity procedure was performed. Glucose, lipid profile, lipid peroxidation, and platelet aggregation were analyzed in the serum. Body composition was determined by the carcass technique.Results: The groups that were supplemented with the BN chow presented less body mass gain and body fat mass, together with lower serum glucose levels. The HG Group presented an increase in blood pressure and a higher platelet aggregation, while the BN supplementation was able to blunt this effect. The HG Group also showed an increase in contractile response that was phenylephrine-induced and a decrease in maximum relaxation that was acetylcholine-induced when compared to the other groups.Conclusion: The BN supplementation was able to prevent an impaired vascular function in the early stages of arterial hypertension, while also improving body composition, serum glucose, and platelet aggregation.
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Bertholletia , Animais , Bertholletia/fisiologia , Pressão Sanguínea , Composição Corporal , Dieta , Suplementos Nutricionais , Glucose/farmacologia , Masculino , Ratos , Ratos WistarRESUMO
The renin-angiotensin (Ang) system (RAS) is a complex hormonal system present locally in several tissues such as cardiovascular organs. RAS deregulation through overactivation of the classical arm [Ang-converting enzyme (ACE)/Ang-II/Ang type 1 receptor (AT1R)] has been linked to the development of cardiovascular diseases and activation of endoplasmic reticulum (ER) stress pathways. The ER stress is a condition that, if unresolved, might lead to heart failure, atherosclerosis, hypertension, and endothelial dysfunction. Accumulated evidence has shown that the RAS modulates the UPR activation. Several studies reported increased ER stress markers in response to Ang-II treatment, in both in vivo and in vitro models. Evidence has also pointed that targeting the RAS classical arm through RAS blockers, gene silencing or genetic models leads to lower levels of ER stress markers. Few studies demonstrated protective effects of the counter-regulatory arm (ACE-2/Ang-(1-7)/Mas receptor) over ER stress. However, the crosstalk mechanisms between the arms of the RAS and ER stress remain unclear. In this review, we sought to explore the classical arm of the RAS as a key mechanism in UPR activation and to suggest a possible protective role of the counter-regulatory arm in mitigating ER stress.
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Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/patologia , Estresse do Retículo Endoplasmático , Sistema Renina-Angiotensina , Animais , Células Endoteliais/metabolismo , Humanos , Modelos Biológicos , Resposta a Proteínas não DobradasRESUMO
AIM: We investigated the effects of high-intensity interval and continuous short-term exercise on body composition and cardiac function after myocardial ischemia-reperfusion injury (IRI) in obese rats. METHODS: Rats fed with a standard chow diet (SC) or high-fat diet (HFD) for 20â¯weeks underwent systolic blood pressure (SBP), glycemia and dual-energy X-ray absorptiometry analyses. Then, animals fed with HFD were subdivided into three groups: sedentary (HFD-SED); moderate-intensity continuous training (HFD-MICT); and high-intensity interval training (HFD-HIIT). Exercised groups underwent four isocaloric aerobic exercise sessions, in which HFD-MICT maintained the intensity continuously and HFD-HIIT alternated it. After exercise sessions, all groups underwent global IRI and myocardial infarct size (IS) was determined histologically. Fat and muscle mass were weighted, and protein levels involved in muscle metabolism were assessed in skeletal muscle. RESULTS: HFD-fed versus SC-fed rats reduced lean body mass by 31% (Pâ¯<â¯0.001), while SBP, glycemia and body fat percentage were increased by 10% (Pâ¯=â¯0.04), 30% (Pâ¯=â¯0.006) and 54% (Pâ¯<â¯0.001); respectively. HFD-induced muscle atrophy was restored in exercised groups, as only HFD-SED presented lower gastrocnemius (32%; Pâ¯=â¯0.001) and quadriceps mass (62%; Pâ¯<â¯0.001) than SC. PGC1-α expression was 2.7-fold higher in HFD-HIIT versus HFD-SED (Pâ¯=â¯0.04), whereas HFD-HIIT and HFD-MICT exhibited 1.7-fold increase in p-mTORSer2481 levels compared to HFD-SED (Pâ¯=â¯0.04). Although no difference was detected among groups for IS (Pâ¯=â¯0.30), only HFD-HIIT preserved left-ventricle developed pressure after IRI (+0.7â¯mmHg; Pâ¯=â¯0.9). SIGNIFICANCE: Short-term exercise, continuous or HIIT, restored HFD-induced muscle atrophy and increased mTOR expression, but only HIIT maintained myocardial contractility following IRI in obese animals.
Assuntos
Composição Corporal/fisiologia , Miocárdio/metabolismo , Animais , Glicemia/metabolismo , Pressão Sanguínea , Dieta Hiperlipídica , Regulação da Expressão Gênica , Testes de Função Cardíaca , Treinamento Intervalado de Alta Intensidade , Humanos , Estudos Longitudinais , Masculino , Modelos Animais , Músculo Esquelético/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/etiologia , Obesidade/etiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Condicionamento Físico Animal , Ratos , Ratos Wistar , Sarcopenia/etiologiaRESUMO
Overactivation of the classical arm of the renin-angiotensin (Ang) system (RAS) occurs during inflammation, oxidative stress and obesity-induced cardiomyopathy. The activation of the protective arm of RAS may act to counterbalance the deleterious effects of the classical RAS. Although aerobic exercise training (AET) shifts the balance of the RAS towards the protective arm, little is known about the molecular adaptations to different volumes of AET. The aim of this study was to evaluate the impact of AET volume on the modulation of RAS, as well as on cardiac biomarkers of oxidative stress and inflammation, in a diet-induced obesity model. Male Wistar rats were fed either control (CON) or high fat (HF) diet for 32 weeks. At week 20, HF group was subdivided into sedentary, low (LEV, 150 min/week) or high (HEV, 300 min/week) exercise volume. After 12 weeks of exercise, body mass gain, systolic blood pressure and heart rate were evaluated, as well as RAS, oxidative stress and inflammation in the heart. Body mass gain, systolic blood pressure and heart rate were higher in HF group when compared with SC group. Both trained groups restored systolic blood pressure and heart rate, but only HEV reduced body mass gain. Regarding the cardiac RAS, the HF group exhibited favoring of the classical arm and both trained groups shifted the balance towards the counterregulatory protective arm. The HF group had higher B1R expression and lower B2R expression than the control group, and B2R expression was reverted in both trained groups. The HF group also presented oxidative stress. The LEV and HEV groups improved the cardiac redox status by reducing Nox 2 and nitrotyrosine expression, but only the LEV group was able to increase the antioxidant defense by increasing Nrf2 signaling. While the HF group presented higher TNF-α, IL-6 and NFκB expression, and lower IL-10 expression, than the SC group, both training protocols improved the inflammatory profile. Although both trained groups improved the deleterious changes related to obesity cardiomyopathy, it is clear that the molecular mechanisms differ between them. Our results suggest that different exercise volumes might reach different molecular targets, and this could be a relevant factor when using exercise to manage obesity.