RESUMO
Sulforaphane is a natural compound with neuroprotective activity, but its effects on hypothalamus remain unknown. In line with this, astrocytes are critical cells to maintain brain homeostasis, and hypothalamic astrocytes are fundamental for sensing and responding to environmental changes involved in a variety of homeostatic functions. Changes in brain functionality, particularly associated with hypothalamic astrocytes, can contribute to age-related neurochemical alterations and, consequently, neurodegenerative diseases. Thus, here, we investigated the glioprotective effects of sulforaphane on hypothalamic astrocyte cultures and hypothalamic cell suspension obtained from aged Wistar rats (24 months old). Sulforaphane showed anti-inflammatory and antioxidant properties, as well as modulated the mRNA expression of astroglial markers, such as aldehyde dehydrogenase 1 family member L1, aquaporin 4, and vascular endothelial growth factor. In addition, it increased the expression and extracellular levels of trophic factors, such as glia-derived neurotrophic factor and nerve growth factor, as well as the release of brain-derived neurotrophic factor and the mRNA of TrkA, which is a receptor associated with trophic factors. Sulforaphane also modulated the expression of classical pathways associated with glioprotection, including nuclear factor erythroid-derived 2-like 2, heme oxygenase-1, nuclear factor kappa B p65 subunit, and AMP-activated protein kinase. Finally, a cell suspension with neurons and glial cells was used to confirm the predominant effect of sulforaphane in glial cells. In summary, this study indicated the anti-aging and glioprotective activities of sulforaphane in aged astrocytes.
Assuntos
Envelhecimento , Astrócitos , Hipotálamo , Isotiocianatos , Fármacos Neuroprotetores , Ratos Wistar , Sulfóxidos , Animais , Isotiocianatos/farmacologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Fármacos Neuroprotetores/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Ratos , Masculino , Células Cultivadas , Antioxidantes/farmacologiaRESUMO
ABSTRACT: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), imposing overload on the right ventricle (RV) and imbalance of the redox state. Our study investigated the influence of treatment with sulforaphane (SFN), found in cruciferous vegetables, on RV remodeling and redox homeostasis in monocrotaline (MCT)-induced PAH. Male Wistar rats were separated into 4 groups: control (CTR); CTR + SFN; MCT; and MCT + SFN. PAH induction was implemented by a single dose of MCT (60 mg/kg intraperitoneally). Treatment with SFN (2.5 mg/kg/day intraperitoneally) started on the seventh day after the MCT injection and persisted for 2 weeks. After 21 days of PAH induction, echocardiographic, hemodynamic, and oxidative stress evaluation was performed. The MCT group showed an increase in RV hypertrophy, RV systolic area, RV systolic, mean pulmonary artery pressure, and PVR and exhibited a decrease in the RV outflow tract acceleration time/ejection time ratio, RV fractional shortening, and tricuspid annular plane systolic excursion compared to CTR ( P < 0.05). SFN-treated PAH attenuated detrimental changes in tricuspid annular plane systolic excursion, mean pulmonary artery pressure, and PVR parameters. Catalase levels and the glutathione/Glutathione disulfide (GSSG) ratio were diminished in the MCT group compared to CTR ( P < 0.05). SFN increased catalase levels and normalized the glutathione/GSSG ratio to control levels ( P < 0.05). Data express the benefit of SFN treatment on the cardiac function of rats with PAH associated with the cellular redox state.
Assuntos
Modelos Animais de Doenças , Isotiocianatos , Monocrotalina , Oxirredução , Estresse Oxidativo , Ratos Wistar , Sulfóxidos , Função Ventricular Direita , Animais , Sulfóxidos/farmacologia , Isotiocianatos/farmacologia , Masculino , Função Ventricular Direita/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/tratamento farmacológico , Homeostase/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Ratos , Pressão Arterial/efeitos dos fármacos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/metabolismo , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/tratamento farmacológico , Disfunção Ventricular Direita/metabolismoRESUMO
ABSTRACT: Myocardial infarction (MI) and pulmonary arterial hypertension (PAH) are 2 prevalent cardiovascular diseases. In both conditions, oxidative stress is associated with a worse prognosis. Pterostilbene (PTE), an antioxidant compound, has been studied as a possible therapy for cardiovascular diseases. This study aims to evaluate the effect of PTE on oxidative stress in the hearts of animals with MI and in the lungs of animals with PAH. Male Wistar rats were used in both models. In the MI model, the experimental groups were sham, MI, and MI + PTE. In the PAH model, the experimental groups were control, PAH, and PAH + PTE. Animals were exposed to MI through surgical ligation of the left coronary artery, or to PAH, by the administration of monocrotaline (60 mg/kg). Seven days after undergoing cardiac injury, the MI + PTE animals were treated with PTE (100 mg/kg day) for 8 days. After this, the heart was collected for molecular analysis. The PAH + PTE animals were treated with PTE (100 mg/kg day) for 14 days, beginning 7 days after PAH induction. After this, the lungs were collected for biochemical evaluation. We found that PTE administration attenuated the decrease in ejection fraction and improved left ventricle end-systolic volume in infarcted animals. In the PAH model, PTE improved pulmonary artery flow and decreased reactive oxygen species levels in the lung. PTE administration promoted protective effects in terms of oxidative stress in 2 experimental models of cardiac diseases: MI and PAH. PTE also improved cardiac function in infarcted rats and pulmonary artery flow in animals with PAH.
Assuntos
Antioxidantes , Modelos Animais de Doenças , Pulmão , Infarto do Miocárdio , Miocárdio , Estresse Oxidativo , Hipertensão Arterial Pulmonar , Ratos Wistar , Estilbenos , Animais , Estresse Oxidativo/efeitos dos fármacos , Masculino , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/fisiopatologia , Estilbenos/farmacologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Hipertensão Arterial Pulmonar/fisiopatologia , Hipertensão Arterial Pulmonar/metabolismo , Antioxidantes/farmacologia , Miocárdio/metabolismo , Miocárdio/patologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Artéria Pulmonar/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Pressão Arterial/efeitos dos fármacos , MonocrotalinaRESUMO
Inflammatory pathways of Toll-like receptor 4 (TLR4) and NLRP3 inflammasome contribute to acute myocardial infarction (AMI) pathophysiology. The hypoxia-inducible factor 1α (HIF-1α), however, is a key transcription factor related to cardioprotection. This study aimed to compare the influence of carvedilol and thyroid hormones (TH) on inflammatory and HIF-1α proteins and on cardiac haemodynamics in the infarcted heart. Male Wistar rats were allocated into five groups: sham-operated group (SHAM), infarcted group (MI), infarcted treated with the carvedilol group (MI + C), infarcted treated with the TH group (MI + TH), and infarcted co-treated with the carvedilol and TH group (MI + C + TH). Haemodynamic analysis was assessed 15 days post-AMI. The left ventricle (LV) was collected for morphometric and Western blot analysis. The MI group presented LV systolic pressure reduction, LV end-diastolic pressure elevation, and contractility index decrease compared to the SHAM group. The MI + C, MI + TH, and MI + C + TH groups did not reveal such alterations compared to the SHAM group. The MI + TH and MI + C + TH groups presented reduced MyD88 and NLRP3 and increased HIF-1α levels. In conclusion, all treatments preserve the cardiac haemodynamic, and only TH, as isolated treatment or in co-treatment with carvedilol, was able to reduce MyD88 and NLRP3 and increase HIF-1α in the infarcted heart.
Assuntos
Fator 88 de Diferenciação Mieloide , Infarto do Miocárdio , Animais , Masculino , Ratos , Carvedilol/farmacologia , Carvedilol/uso terapêutico , Fator 88 de Diferenciação Mieloide/metabolismo , Infarto do Miocárdio/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Wistar , Hormônios TireóideosRESUMO
Oxidative stress is involved in increased pulmonary vascular resistance (PVR) and right ventricular (RV) hypertrophy, characteristics of pulmonary arterial hypertension (PAH). Copaiba oil, an antioxidant compound, could attenuate PAH damage. This study's aim was to determine the effects of copaiba oil on lung oxidative stress, PVR, and mean pulmonary arterial pressure (mPAP) in the monocrotaline (MCT) model of PAH. Male Wistar rats (170 g, n = 7/group) were divided into four groups: control, MCT, copaiba oil, and MCT + copaiba oil (MCT-O). PAH was induced by MCT (60 mg/kg i.p.) and, after 1 week, the treatment with copaiba oil (400 mg/kg/day gavage) was started for 14 days. Echocardiographic and hemodynamic measurements were performed. RV was collected for morphometric evaluations and lungs and the pulmonary artery were used for biochemical analysis. Copaiba oil significantly reduced RV hypertrophy, PVR, mPAP, and antioxidant enzyme activities in the MCT-O group. Moreover, increased nitric oxide synthase and decreased NADPH oxidase activities were observed in the MCT-O group. In conclusion, copaiba oil was able to improve the balance between nitric oxide and reactive oxygen species in lungs and the pulmonary artery and to reduce PVR, which could explain a decrease in RV hypertrophy in this PAH model.
Assuntos
Hipertensão Pulmonar , Óleos Voláteis , Hipertensão Arterial Pulmonar , Ratos , Masculino , Animais , Ratos Wistar , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Monocrotalina/efeitos adversos , Óxido Nítrico , Antioxidantes/farmacologia , Disponibilidade Biológica , Pulmão , Artéria Pulmonar , Hipertensão Pulmonar Primária Familiar , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/tratamento farmacológico , Óleos Voláteis/farmacologia , Modelos Animais de DoençasRESUMO
Sulforaphane is a natural compound that presents anti-inflammatory and antioxidant properties, including in the central nervous system (CNS). Astroglial cells are involved in several functions to maintain brain homeostasis, actively participating in the inflammatory response and antioxidant defense systems. We, herein, investigated the potential mechanisms involved in the glioprotective effects of sulforaphane in the C6 astrocyte cell line, when challenged with the inflammogen, lipopolysaccharide (LPS). Sulforaphane prevented the LPS-induced increase in the expression and/or release of pro-inflammatory mediators, possibly due to nuclear factor κB and hypoxia-inducible factor-1α activation. Sulforaphane also modulated the expressions of the Toll-like and adenosine receptors, which often mediate inflammatory processes induced by LPS. Additionally, sulforaphane increased the mRNA levels of nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO1), both of which mediate several cytoprotective responses. Sulforaphane also prevented the increase in NADPH oxidase activity and the elevations of superoxide and 3-nitrotyrosine that were stimulated by LPS. In addition, sulforaphane and LPS modulated superoxide dismutase activity and glutathione metabolism. Interestingly, the anti-inflammatory and antioxidant effects of sulforaphane were blocked by HO1 pharmacological inhibition, suggesting its dependence on HO1 activity. Finally, in support of a glioprotective role, sulforaphane prevented the LPS-induced decrease in glutamate uptake, glutamine synthetase activity, and glial-derived neurotrophic factor (GDNF) levels, as well as the augmentations in S100B release and Na+, K+ ATPase activity. To our knowledge, this is the first study that has comprehensively explored the glioprotective effects of sulforaphane on astroglial cells, reinforcing the beneficial effects of sulforaphane on astroglial functionality.
Assuntos
Lipopolissacarídeos , Transdução de Sinais , Animais , Células Cultivadas , Isotiocianatos/farmacologia , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , SulfóxidosRESUMO
Enhanced sympathetic system activation mediated by norepinephrine (NE) contributes to adverse cardiac remodeling leading to oxidative stress and cell death, progressing to heart failure. Natural antioxidants may help maintain redox balance, attenuating NE-mediated cardiac cell damage. In the present study, we evaluated the effect of a blueberry extract (BBE) on H9c2 cardiac cells exposed to NE on cell death, oxidative stress status and its major signaling pathways. H9c2 cells were pre-incubated with 50 µg/ml of BBE for 4 h and maintained in the presence of 100 µM NE for 24 h. NE exposure resulted in increased caspase 3/7 activity. This was associated with reduced protein expression of antioxidants catalase, superoxide dismutase and glutathione peroxidase and increase in 4-hydroxynonenal adduct formation. NE led to increased activity of Protein kinase B (Akt), Forkhead box O3a and AMP-activated protein kinase alpha and decreased activity of Signal transducer and activator of transcription 3. BBE prevented caspases activation and abrogated NE-induced increase in oxidative stress, as well as attenuated the increase in Akt. Based on these findings, it is concluded that BBE promoted cardioprotection of H9c2 cells in an in vitro model of NE-induced oxidative damage, suggesting a cardioprotective role for BBE in response to NE exposure.
Assuntos
Apoptose/efeitos dos fármacos , Mirtilos Azuis (Planta)/química , Mioblastos Cardíacos/metabolismo , Norepinefrina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Extratos Vegetais/química , RatosRESUMO
ABSTRACT: Sulforaphane (SFN) is a natural exogenous antioxidant from cruciferous vegetables already shown to improve cardiac function in cardiovascular diseases. The aim of this study was to analyze the effect of SFN treatment on the cardiac function in 2 experimental models of heart disease, ischemia/reperfusion (I/R) and myocardial infarction (MI), and whether an improvement of the cardiac function could be associated with a modulation of calcium-handling proteins. The study was divided into 2 main experiments: experiment 1, ex vivo with the I/R model and experiment 2, in vivo with the MI model. In the I/R model, rats were divided into control and SFN (0.5 mg/kg/d intraperitoneally for 3 days) groups, and the hearts were submitted to global ischemia (20 minutes) followed by reperfusion (20 minutes) in a Langendorff apparatus. SFN did not change left ventricle systolic and diastolic pressures but increased the contractility and relaxation indexes after 20 minutes of reperfusion. These functional changes were accompanied by a decreased protein expression of ryanodine receptor (RyR) and increased expression of p-phospholamban/phospholamban ratio, without alteration in the sarco/endoplasmic calcium ATPase expression. In the MI model, rats were randomly divided into Sham, MI (MI induced by left coronary artery ligation), Sham + SFN (5 mg/kg/d intraperitoneally for 25 days), and MI + SFN groups. Although SFN did not affect cardiac function, it led to a decreased RyR protein expression and reactive oxygen species levels in the left ventricular of the MI + SFN group. These data indicate that SFN modulates calcium-handling proteins and, thus, cardiac inotropism/lusitropism especially when administered previously to an ischemic event.
Assuntos
Cálcio , Infarto do Miocárdio , Animais , Cálcio/metabolismo , Isotiocianatos , Modelos Teóricos , Infarto do Miocárdio/metabolismo , Ratos , Reperfusão , SulfóxidosRESUMO
PURPOSE: Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary vascular resistance and right ventricle (RV) failure. In this context, oxidative stress is an essential element contributing to PAH's pathophysiology. Thus, blueberry (BB), which has a high antioxidant capacity, emerges as a natural therapeutic approach in PAH. This work evaluated the effect of BB extract on redox balance in RV in a PAH's animal model. METHODS: Male Wistar rats (200 ± 20 g) (n = 72) were randomized into eight groups: control (CTR); monocrotaline (MCT); CTR and MCT treated at doses of 50, 100, and 200 mg/kg BB. PAH was induced by administration of MCT (60 mg/kg, intraperitoneal). Rats were treated with BB orally for 5 weeks (2 weeks before monocrotaline and 3 weeks after monocrotaline injection). On day 35, rats were submitted to echocardiography and catheterization, then euthanasia and RV harvesting for biochemical analyses. RESULTS: RV hypertrophy, observed in the MCT groups, was reduced with BB treatment. MCT elevated RV systolic pressure and pressure/time derivatives, while the intervention with BB decreased these parameters. PAH decreased RV output and pulmonary artery outflow acceleration/ejection time ratio, while increased RV diameters, parameters restored by BB treatment. Animals from the MCT group showed elevated lipid peroxidation and NADPH oxidase activity, outcomes attenuated in animals treated with BB, which also led to increased catalase activity. CONCLUSION: Treatment with BB partially mitigated PAH, which could be associated with improvement of RV redox state. Such findings constitute an advance in the investigation of the role of BB extract in chronic progressive cardiovascular diseases that involve the redox balance, such as PAH.
Assuntos
Mirtilos Azuis (Planta) , Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Animais , Modelos Animais de Doenças , Ventrículos do Coração , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Oxirredução , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
Vitamin C (Vit C) is an ideal antioxidant as it is easily available, water soluble, very potent, least toxic, regenerates other antioxidants particularly Vit E, and acts as a cofactor for different enzymes. It has received much attention due to its ability in limiting reactive oxygen species, oxidative stress, and nitrosative stress, as well as it helps to maintain some of the normal metabolic functions of the cell. However, over 140 clinical trials using Vit C in different pathological conditions such as myocardial infarction, gastritis, diabetes, hypertension, stroke, and cancer have yielded inconsistent results. Such a divergence calls for new strategies to establish practical significance of Vit C in heart failure or even in its prevention. For a better understanding of Vit C functioning, it is important to revisit its transport across the cell membrane and subcellular interactions. In this review, we have highlighted some historical details of Vit C and its transporters in the heart with a particular focus on heart failure in cancer chemotherapy.
Assuntos
Ácido Ascórbico , Insuficiência Cardíaca , Antioxidantes/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Estresse Oxidativo , Espécies Reativas de OxigênioRESUMO
Acute myocardial infarction (AMI) is one of the major causes of heart failure and mortality. Glucocorticoids administration post-infarction has long been proposed, but it has shown conflicting results so far. This controversy may be associated with the glucocorticoid type and the period when it is administered. To elucidate these, the present aims to evaluate if the brief methylprednisolone acetate administration is determinant for heart adaptation after AMI. Male Wistar rats were divided into 3 groups: sham-operated (SHAM); infarcted (AMI); infarcted treated with methylprednisolone acetate (AMI+M). Immediately after surgery, the AMI+M group received a single dose of methylprednisolone acetate (40 mg/kg i.m.). After 56 days, the cardiac function was assessed and lungs, liver and heart were collected to determine rates of hypertrophy and congestion. Heart was used for oxidative stress and metalloproteinase activity analyses. Methylprednisolone acetate attenuated matrix metalloproteinase-2 activity, cardiac dilatation, and prevented the onset of pulmonary congestion, as well as avoided cardiac hypertrophy. Our data indicate that administration of methylprednisolone acetate shortly after AMI may be a therapeutic alternative for attenuation of detrimental ventricular remodeling.
Assuntos
Metilprednisolona , Infarto do Miocárdio , Animais , Masculino , Metaloproteinase 2 da Matriz , Metilprednisolona/uso terapêutico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Miocárdio , Ratos , Ratos Wistar , Remodelação VentricularRESUMO
NEW FINDINGS: What is the central question of this study? Does thyroid hormone treatment given after myocardial infarction preserve left ventricular function and treadmill exercise performance, and improve parameters of oxidative stress in the right ventricle and lungs of Wistar rats? What is the main finding and its importance? Thyroid hormone treatment improved the performance of the maximum exercise test in infarcted rats and induced effects in the heart and lungs that were similar to those observed with exercise training. This suggests there is a significant value of thyroid hormones for preserving exercise tolerance after myocardial infarction. ABSTRACT: Left ventricular myocardial infarction (MI) provokes damage in the heart and in other tissues, such as right ventricle and lungs. The present study elucidated whether thyroid hormone treatment (THT) may present positive effects in heart and lungs after MI, and whether or not these effects are similar to those of exercise training (ET). Male Wistar rats were divided into four groups: sham operated (SHAM), infarcted (MI), infarcted + exercise training (MIE), and infarcted + thyroid hormones (MIH). A maximum exercise test, left ventricle echocardiography, pulmonary histology, and oxidative stress in the right ventricle and lung were evaluated. THT and ET both reduced left ventricular dilatation and end-diastolic wall stress indexes to a similar extent. MI accentuated the content of macrophages and inflammatory infiltrate in the lungs, which was partially prevented in the MIH and MIE groups. THT and ET presented similar effects in the heart and lungs, and both improved the performance of the maximum exercise test in infarcted animals.
Assuntos
Teste de Esforço , Infarto do Miocárdio/terapia , Condicionamento Físico Animal , Hormônios Tireóideos/farmacologia , Função Ventricular Esquerda , Animais , Ecocardiografia , Coração , Pulmão , Masculino , Miocárdio , Estresse Oxidativo , Ratos WistarRESUMO
Cellular death and survival signaling plays a key role in the progress of adverse cardiac remodeling after acute myocardial infarction (AMI). Therapeutic strategies, such as co-treatment with beta-blocker carvedilol and thyroid hormones (THs), give rise to new approaches that can sustain the cellular homeostasis after AMI. Therefore, we sought to investigate the effects of carvedilol and TH co-administration on apoptosis and survival proteins and on cardiac remodeling after AMI. Male Wistar rats were distributed in 5 groups as follows: sham-operated group (SHAM), infarcted group (MI), infarcted plus carvedilol group (MI+C), infarcted plus TH group (MI+TH), and infarcted plus carvedilol and TH co-treatment group (MI+C+TH). Echocardiographic analysis was performed, and hearts were collected for western blot evaluation. The MI group presented systolic posterior wall thickness loss, an increase in the wall tension index, and an increase in atrial natriuretic peptide tissue levels than the SHAM group. However, in the MI+C+TH group, these parameters were equally to the SHAM group. Moreover, whereas the MI group showed Bax protein expression elevated in relation to the SHAM group, the MI+C+TH group presented Bax reduction and also Akt activation compared with the MI group. In addition, the MI+TH group revealed beta-1 adrenergic receptor (ß1AR) upregulation compared with the MI and MI+C groups, whereas the MI+C+TH group presented lower levels of ß1AR in relation to the SHAM and MI+TH groups. In conclusion, we suggest that carvedilol and TH co-administration may mediate its cardioprotective effects against adverse cardiac remodeling post-AMI through the Bax reduction, Akt activation, and ß1AR decrease.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/efeitos dos fármacos , Carvedilol/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Tiroxina/farmacologia , Tri-Iodotironina/farmacologia , Animais , Modelos Animais de Doenças , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt , Ratos Wistar , Receptores Adrenérgicos alfa 1/efeitos dos fármacos , Receptores Adrenérgicos alfa 1/metabolismo , Transdução de SinaisRESUMO
Among the different cardiovascular disease complications, atherosclerosis-induced myocardial infarction (MI) is the major contributor of heart failure (HF) and loss of life. This review presents short- and long-term features of post-MI in human hearts and animal models. It is known that the heart does not regenerate, and thus loss of cardiac cells after an MI event is permanent. In survivors of a heart attack, multiple neurohumoral adjustments as well as simultaneous remodeling in both infarcted and noninfarcted regions of the heart help sustain pump function post-MI. In the early phase, migration of inflammatory cells to the infarcted area helps repair and remove the cell debris, while apoptosis results in the elimination of damaged cardiomyocytes, and there is an increase in the antioxidant response to protect the survived myocardium against oxidative stress (OS) injury. However, in the late phase, it appears that there is a relative increase in OS and activation of the innate inflammatory response in cardiomyocytes without any obvious inflammatory cells. In this late stage in survivors of MI, a progressive slow activation of these processes leads to apoptosis, fibrosis, cardiac dysfunction, and HF. Thus, this second phase of an increase in OS, innate inflammatory response, and apoptosis results in wall thinning, dilatation, and consequently HF. It is important to note that this inflammatory response appears to be innate to cardiomyocytes. Blunting of this innate immune cardiomyocyte response may offer new hope for the management of HF.
Assuntos
Insuficiência Cardíaca/imunologia , Imunidade Inata , Infarto do Miocárdio/imunologia , Animais , Apoptose , Insuficiência Cardíaca/etiologia , Humanos , Infarto do Miocárdio/etiologia , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/metabolismo , Estresse OxidativoRESUMO
OBJECTIVE: The purpose of our study was to evaluate the effect of manually assisted lumbar spinal manipulation therapy on tactile allodynia, peripheral nerve functional recovery, and oxidative markers in rats exposed to knee immobilization-inducing hypersensitivity. METHODS: Tactile allodynia and sciatic, tibial, and peroneal functional indices were assessed before the knee joint immobilization, 24 hours after the knee cast removal, and 24 hours after 3 weeks of lumbar therapy with the Activator Adjusting Instrument, model 4 (AAI 4). Subsequently, the blood was collected from each rat, and oxidative markers such as lipid hydroperoxide levels; nitric oxide metabolites; and superoxide dismutase, catalase, and glutathione peroxidase activities were assessed. RESULTS: The AAI 4 improved the immobilization-induced allodynia and recovered the peripheral nerve functional indices impaired after knee immobilization. Immobilized rats treated with AAI 4 therapy presented a lack of significant changes in lipid hydroperoxides and nitric oxide metabolites in the plasma contrasting with rats that were kept freely in their cages, with no therapy applied, which presented elevated lipid hydroperoxides levels. Also, the antioxidant catalase enzymatic activity decreased in the blood of rats immobilized and treated with AAI 4. CONCLUSION: These results suggest that manually assisted lumbar spinal manipulation therapy modulates systemic oxidative stress, which possibly contributes to the analgesia and recovery of peripheral nerve functionality.
Assuntos
Hiperalgesia/terapia , Plexo Lombossacral/fisiologia , Manipulação da Coluna , Animais , Biomarcadores/sangue , Catalase/sangue , Glutationa Peroxidase/sangue , Hiperalgesia/etiologia , Imobilização/efeitos adversos , Peróxidos Lipídicos/sangue , Modelos Animais , Óxido Nítrico/sangue , Nitritos/sangue , Nociceptividade , Estresse Oxidativo , Ratos , Ratos Wistar , Joelho de Quadrúpedes , Superóxido Dismutase/sangueRESUMO
Our aim was to investigate transitory and delayed exercise effects on serum extracellular vesicles (EVs) in aging process. Male Wistar rats of 3-, 21-, and 26-month old were allocated into exercised and sedentary groups. The exercise protocol consisted in a daily moderate treadmill exercise (20 min daily during 2 weeks). Trunk blood was collected 1 and 18 h after the last exercise session, and circulating EVs were obtained. CD63 levels and acetylcholinesterase (AChE) activity were used as markers of exosome, a subtype of EVs. In addition, the quantification of amyloid-ß (Aß) levels and the oxidative status parameters, specifically reactive species content, superoxide dismutase (SOD) activity, and SOD1 content were evaluated. Aged rats showed reduced CD63 levels and increased AChE activity in circulating exosomes compared to young ones. Moreover, higher reactive species levels were found in circulating EVs of aged rats. Delayed exercise effects were observed on peripheral EVs, since CD63, reactive species content, and AChE activity were altered 18 h after the last exercise session. Our results suggest that the healthy aging process can modify circulating EVs profile, and exercise-induced beneficial effects may be related to its modulation on EVs.
Assuntos
Envelhecimento/sangue , Micropartículas Derivadas de Células/metabolismo , Exossomos/metabolismo , Condicionamento Físico Animal , Acetilcolinesterase/sangue , Peptídeos beta-Amiloides/sangue , Animais , Proteínas Ligadas por GPI/sangue , Masculino , Ratos , Ratos Wistar , Tetraspanina 30/sangueRESUMO
There is an increase in oxidative stress and apoptosis signaling during the transition from hypertrophy to right ventricular (RV) failure caused by pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). In this study, it was evaluated the action of copaiba oil on the modulation of proteins involved in RV apoptosis signaling in rats with PAH. Male Wistar rats (±170 g, n = 7/group) were divided into 4 groups: control, MCT, copaiba oil, and MCT + copaiba oil. PAH was induced by MCT (60 mg/kg intraperitoneally) and, 7 days later, treatment with copaiba oil (400 mg/kg by gavage) was given for 14 days. Echocardiographic and hemodynamic measurements were performed, and the RV was collected for morphometric evaluations, oxidative stress, apoptosis, and cell survival signaling, and eNOS protein expression. Copaiba oil reduced RV hypertrophy (24%), improved RV systolic function, and reduced RV end-diastolic pressure, increased total sulfhydryl levels and eNOS protein expression, reduced lipid and protein oxidation, and the expression of proteins involved in apoptosis signaling in the RV of MCT + copaiba oil as compared to MCT group. In conclusion, copaiba oil reduced oxidative stress, and apoptosis signaling in RV of rats with PAH, which may be associated with an improvement in cardiac function caused by this compound.
Assuntos
Apoptose/efeitos dos fármacos , Fármacos Cardiovasculares/farmacologia , Fabaceae , Hipertensão Pulmonar/tratamento farmacológico , Hipertrofia Ventricular Direita/prevenção & controle , Monocrotalina , Miocárdio , Óleos de Plantas/farmacologia , Disfunção Ventricular Direita/prevenção & controle , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Fármacos Cardiovasculares/isolamento & purificação , Modelos Animais de Doenças , Fabaceae/química , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/isolamento & purificação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Disfunção Ventricular Direita/induzido quimicamente , Disfunção Ventricular Direita/metabolismo , Disfunção Ventricular Direita/patologia , Proteína X Associada a bcl-2/metabolismoRESUMO
The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg-1 i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor ß (ER-ß). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.
Assuntos
Antioxidantes/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Monocrotalina/efeitos adversos , Ovariectomia/efeitos adversos , Adaptação Fisiológica/efeitos dos fármacos , Animais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Remodelação Ventricular/efeitos dos fármacosRESUMO
BACKGROUND: Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA. MATERIALS AND METHODS: Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. RESULTS: There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). CONCLUSIONS: Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA.
Assuntos
Aorta Abdominal/enzimologia , Aneurisma da Aorta Abdominal/enzimologia , Arteriopatias Oclusivas/enzimologia , Estresse Oxidativo , Idoso , Antioxidantes/análise , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/diagnóstico , Arteriopatias Oclusivas/diagnóstico , Biomarcadores/análise , Estudos de Casos e Controles , Catalase/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidases/análise , Nitritos/análise , Peroxidase/análise , Estudos Prospectivos , Espécies Reativas de Oxigênio/análise , Superóxido Dismutase/análiseRESUMO
Intense exercise generates an imbalance in the redox system. However, chronic exercise can yield antioxidant adaptations. A few studies with humans have investigated the effects of antioxidant diets on athletes. Therefore we compared the effects of two dietary interventions on oxidative stress in competitive triathletes. Thirteen male triathletes were selected and divided into 2 groups: one that had a regular antioxidant diet (RE-diet) and the other that had a high antioxidant diet (AO-diet). The diet period was 14 days and blood samples were collected before and after this period. The AO-diet provided twice the dietary reference intake (DRI) of α-tocopherol (30 mg), five times the DRI of ascorbic acid (450 mg), and twice the DRI of vitamin A (1800 g), while the RE-diet provided the DRI of α-tocopherol (15 mg), twice the DRI of ascorbic acid (180 mg) and the DRI of vitamin A (900 µg). The oxidative stress parameters evaluated were: thiobarbituric acid reactive substances (TBARS), total reactive antioxidant potential (TRAP), total sulfhydryl, carbonyl, superoxide dismutase (SOD) activity, hydrogen peroxide consumption and glutathione peroxidase (GPx) activity. We observed, after the diet period, an increase in sulfhydryl, TRAP, TBARS and SOD activity, and a decrease in carbonyl levels. However, no changes were found in hydrogen peroxide consumption or GPx activity. We concluded that antioxidant-enriched diets can improve the redox status of triathletes.