RESUMO
BACKGROUND: Pterostilbene (PS), a natural and antioxidant polyphenolic compound emerges as a promising intervention in improving the myocardial infarction (MI) damages. OBJETIVES: This study aimed to evaluate PS actions in promoting redox homeostasis in lungs and right ventricle (RV) of infarcted animals. METHODS: Male Wistar rats (60 day-old) were randomized into three groups: SHAM, MI (infarcted), and MI+PS (MI+pterostilbene). Seven days after MI procedure, rats were treated with PS (100 mg/kg/day) via gavage for eight days. Animals were euthanized and the lungs and RV were harvested for analyses of redox balance (Differences were considered significant when p<0.05). RESULTS: Our results show that MI triggers a redox disruption scenario in RV and lungs, which can contribute to MI-induced damage on these organs. Consistently, PS mitigated oxidative stress and restored antioxidant defenses (GSH in lungs: SHAM= 0.79±0.07; MI=0.67±0.05; MI+PS=0.86±0.14; p<0.05), indicating its protective role in this scenario. CONCLUSIONS: Our work evidences the PS potential use as an adjuvant therapeutic approach after MI focusing on protecting pulmonary and right-sided heart tissues.
FUNDAMENTO: O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). OBJETIVO: Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. MÉTODOS: Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p<0,05). RESULTADOS: Nossos resultados mostram que o IAM desencadeia a interrupção redox no VD e nos pulmões, o que pode contribuir para danos induzido pelo IAM nesses órgãos. Consistentemente, o PS mitigou o estresse oxidativo e restaurou as defesas antioxidantes (Glutationa GSH nos pulmões: SHAM = 0,79 ± 0,07; IAM = 0,67 ± 0,05; IAM + PS = 0,86 ± 0,14; p<0,05), indicando seu papel protetor neste cenário. CONCLUSÃO: Nosso trabalho evidencia o potencial do uso de PS como abordagem terapêutica adjuvante após IAM para proteção dos tecidos pulmonares e cardíacos direitos.
Assuntos
Ventrículos do Coração , Pulmão , Infarto do Miocárdio , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Ventrículos do Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Ratos , Ratos WistarRESUMO
CONTEXT: Infarction leads to a decrease in NO bioavailability in the erythrocytes. Thyroid hormones (TH) present positive effects after infarction. However, there are no studies evaluating the effects of cardioprotective doses of TH in the erythrocytes after infarction. OBJECTIVE: This study aimed to evaluate the effects of TH in NO bioavailability and oxidative stress parameters in the erythrocytes of infarcted rats. MATERIAL AND METHODS: Wistar rats were allocated into the three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). AMIT rats received T4 and T3 for 12 days by gavage. Subsequently, the animals were evaluated by echocardiography and the LV and erythrocytes were collected. RESULTS: TH improved NO bioavailability and increased catalase activity in the erythrocytes. Besides that, TH increased HIF-1α in the heart. CONCLUSION: TH seems to be positive for erythrocytes preventing a decrease in NO bioavailability and increasing antioxidant enzymatic defense after infarction.
Assuntos
Antioxidantes , Infarto do Miocárdio , Animais , Ratos , Catalase , Eritrócitos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/metabolismo , Ratos Wistar , Hormônios Tireóideos/farmacologia , Óxido NítricoRESUMO
Resumo Fundamento O pterostilbeno (PS), um composto polifenólico natural e antioxidante, surge como uma intervenção promissora para minimizar danos do infarto agudo do miocárdio (IAM). Objetivo Este estudo teve como objetivo avaliar o desempenho do PS na promoção da homeostase redox nos pulmões e no ventrículo direito (VD) de animais infartados. Métodos Ratos Wistar machos (60 dias de idade) foram randomizados em três grupos: SHAM, IAM (infarto) e IAM+PS (IAM + pterostilbeno). Sete dias após o procedimento de IAM, os ratos foram tratados com PS (100 mg/kg/dia) por gavagem por oito dias. Os animais foram depois sacrificados e os pulmões e VD foram coletados para análise do balanço redox (diferenças foram consideradas significativas quando p<0,05). Resultados Nossos resultados mostram que o IAM desencadeia a interrupção redox no VD e nos pulmões, o que pode contribuir para danos induzido pelo IAM nesses órgãos. Consistentemente, o PS mitigou o estresse oxidativo e restaurou as defesas antioxidantes (Glutationa - GSH nos pulmões: SHAM = 0,79 ± 0,07; IAM = 0,67 ± 0,05; IAM + PS = 0,86 ± 0,14; p<0,05), indicando seu papel protetor neste cenário. Conclusão Nosso trabalho evidencia o potencial do uso de PS como abordagem terapêutica adjuvante após IAM para proteção dos tecidos pulmonares e cardíacos direitos.
Abstract Background Pterostilbene (PS), a natural and antioxidant polyphenolic compound emerges as a promising intervention in improving the myocardial infarction (MI) damages. Objetives This study aimed to evaluate PS actions in promoting redox homeostasis in lungs and right ventricle (RV) of infarcted animals. Methods Male Wistar rats (60 day-old) were randomized into three groups: SHAM, MI (infarcted), and MI+PS (MI+pterostilbene). Seven days after MI procedure, rats were treated with PS (100 mg/kg/day) via gavage for eight days. Animals were euthanized and the lungs and RV were harvested for analyses of redox balance (Differences were considered significant when p<0.05). Results Our results show that MI triggers a redox disruption scenario in RV and lungs, which can contribute to MI-induced damage on these organs. Consistently, PS mitigated oxidative stress and restored antioxidant defenses (GSH in lungs: SHAM= 0.79±0.07; MI=0.67±0.05; MI+PS=0.86±0.14; p<0.05), indicating its protective role in this scenario. Conclusions Our work evidences the PS potential use as an adjuvant therapeutic approach after MI focusing on protecting pulmonary and right-sided heart tissues.
Assuntos
Animais , Masculino , Ratos , Estilbenos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Ratos WistarRESUMO
Studies have shown a cardioprotective role of thyroid hormones (THs) in cardiac remodeling after acute myocardial infarction (MI). However, there is no data in the literature examining the influence of TH administration on the aortic tissue in an animal model of MI. This study aimed to evaluate the effects of thyroid hormones on the aorta after MI. Male Wistar rats were divided into a sham group (SHAM), infarcted group (AMI), sham+TH (SHAMT) and AMI+TH (AMIT). After MI, the animals received T3 and T4 (2 and 8µg/100g/day, respectively) by oral gavage for 12 days. Later, the animals underwent echocardiography and euthanasia and the aorta was collected for molecular and biochemical analysis. T3 and T4 administration increased the expression of the pro-angiogenic proteins vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF-1α) in the aorta of AMIT rats when compared with AMI. With respect to TH receptors, AMI rats presented a decrease in TRß levels, which was prevented by the hormonal administration. In AMIT rats, both TRα and TRß levels were increased when compared with the AMI group. Reactive oxygen species levels and NADPH oxidase activity were decreased in both treated groups when compared with the non-treated animals. TH administration after MI may improve angiogenic signaling in the aorta as well as the responsiveness of this vessel to T3 and T4. These positive effects in the aorta may result in additional protection for the cardiovascular system in the context of cardiac ischaemic injury.
Assuntos
Aorta/efeitos dos fármacos , Aorta/metabolismo , Infarto do Miocárdio/patologia , Hormônios Tireóideos/farmacologia , Angiotensina I/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Xantina Oxidase/metabolismoRESUMO
UNLABELLED: Right ventricle (RV) dysfunction post-myocardial infarction (MI) was associated with a worsened prognosis. In this scenario, reactive oxygen species (ROS) are related with the progression from MI to heart failure. Previous work showed that thyroid hormones (TH) are cardioprotective after MI. AIMS: This study aims to investigate the effect of T3 and T4 administration on oxidative stress and angiogenesis parameters in the RV after MI. MAIN METHODS: Wistar rats were allocated into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT), and infarcted+TH (AMIT). The treated groups received T3 (2 µg/100g/day) and T4 (8 µg/100g/day) by gavage for 26 days. After this, echocardiographic analysis was performed and the RV was collected to western blot and biochemical analysis. KEY FINDINGS: Infarcted treated rats showed RV hypertrophy compared with AMI and SHAMT. Hydrogen peroxide levels were decrease and SOD activity and expression were increased in the infarcted treated rats. Besides that, the hormonal administration increased eNOS expression and prevented the reduction of VEGF levels in AMIT rats. SIGNIFICANCE: In conclusion, TH seems to improve oxidative stress parameters, to promote physiological hypertrophy and to increase the expression of proteins involved with angiogenesis in the right heart.
Assuntos
Infarto do Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Hormônios Tireóideos/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Animais , Ecocardiografia , Peróxido de Hidrogênio/metabolismo , Hipertrofia Ventricular Direita/diagnóstico por imagem , Hipertrofia Ventricular Direita/patologia , Neovascularização Patológica/patologia , Óxido Nítrico Sintase Tipo III/biossíntese , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Tiroxina/uso terapêutico , Tri-Iodotironina/uso terapêuticoRESUMO
Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction.