Sulforaphane Improves Redox Homeostasis and Right Ventricular Contractility in a Model of Pulmonary Hypertension.

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.

Cardioprotective doses of thyroid hormones improve NO bioavailability in erythrocytes and increase HIF-1α expression in the heart of infarcted rats.

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.

Isso já está superado!: A justificação do preconceito no setor bancário / This is overcome!: Prejudice justification in banks which have diversity management programs / ¡Eso ya está superado!: La justificación del prejuicio en organizaciones bancarias que tienen programas de gestión de la diversidad

O objetivo deste artigo foi compreender a maneira pela qual se manifestam as estratégias de justificação e negação do preconceito em organizações bancárias no sul de MG, que possuem programas de gestão da diversidade. Empiricamente, realizou-se uma pesquisa qualitativa na qual foram feitas 15 entrevistas semiestruturadas com bancários. Os dados foram analisados por meio da Análise do Discurso. Os resultados evidenciam que o preconceito está presente no contexto bancário, no entanto, os entrevistados não reconhecem que ele exista no ambiente em que trabalham, por isso, buscam maneiras de justificá-lo e negá-lo. A justificação ocorre por meio da mobilização de estratégias de culpabilização dos "outros" e das próprias minorias, da reprodução da ideologia da meritocracia e da naturalização e "superação" do preconceito. As estratégias de justificação e negação do preconceito servem como elementos que sustentam a manutenção das ideologias hegemônicas das políticas de diversidade das organizações.

The purpose of this article was to understand the way in which prejudice denial and justification strategies occur inside banks in the South of Minas Gerais, these being the ones that have diversity management programs. Empirically speaking, a qualitative study was done in which 15 semi-structured interviews were conducted with bank clerks. The results show that prejudice is present in the bank environment, however, the interviewees do not recognize that it exists in their workplace, and consequently, they look for ways to deny it and justify it. Justification takes the form of strategies of blaming others and the minorities themselves, the ideological reproduction of meritocracy, and the naturalization and overcoming of prejudice. Prejudice denial and justification strategies serve as elements that support the maintenance of hegemonic ideologies of the diversity policies of the organizations.

El objetivo de este artículo fue comprender la manera en que se manifiestan las estrategias de justificación y negación del prejuicio en organizaciones bancarias en el sur de Minas Gerais, Brasil, que poseen programas de gestión de la diversidad. Empíricamente, se realizó una investigación cualitativa en la que fueran hechas 15 entrevistas semiestructuradas con banqueros. Los datos se analizaron mediante el Análisis del Discurso. Los resultados evidencian que el prejuicio está presente en el contexto bancario, sin embargo, los encuestados no reconocen que existe en el ambiente en el que trabajan, por lo que buscan maneras de justificarlo y negarlo. La justificación ocurre por la movilización de estrategias de culpabilización de los "otros" y de las propias minorías, de la reproducción de la ideología de la meritocracia y de la naturalización y "superación" de los prejuicios. Las estrategias de justificación y negación del prejuicio sirven como elementos que sostienen el mantenimiento de las ideologías hegemónicas de las políticas de diversidad de organizaciones.

Decreased PGC1- α levels and increased apoptotic protein signaling are associated with the maladaptive cardiac hypertrophy in hyperthyroidism.

Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-α, TNF-α, MyD88, p-NFκB, NFκB, p-p38, and p38. Reduced expression of p53 and PGC1-α was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-α and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy.

Effects of ovariectomy on antioxidant defence systems in the right ventricle of female rats with pulmonary arterial hypertension induced by monocrotaline.

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.

Thyroid hormones decrease the proinflammatory TLR4/NF-κß pathway and improve functional parameters of the left ventricle of infarcted rats.

Myocardial infarction leads to oxidative stress and promotes activation of the TLR4/NF-κß proinflammatory pathway. Thyroid hormones (TH) are known to be cardioprotective after infarction. However, there are no studies evaluating whether TH could modulate this pathway in the heart. This study aimed to verify the effect of thyroid hormones on the TLR4/NF-κß pathway after myocardial infarction. Male Wistar rats were allocated into the following groups: Sham-operated (SHAM), sham-operated + TH (SHAMT), infarcted (AMI) and infarcted + TH (AMIT). The treated rats received T4 and T3 (8 and 2 µg 100 g-1 day-1) for 12 days by gavage. Subsequently, the animals were evaluated by echocardiography and euthanized, and the left ventricle was collected for biochemical and molecular analyses. TH modulates TLR4/NF-κß expression in the infarcted hearts of rats and decreases xanthine oxidase expression. These effects were related to cardiac functional improvement after infarction. The cardioprotective effects of T3 and T4 seem to involve an anti-inflammatory action.

Long-term T3 and T4 treatment as an alternative to aerobic exercise training in improving cardiac function post-myocardial infarction.

Here we aimed to compare the beneficial effects of T3 and T4 hormone treatment to those provided by aerobic exercise training in Wistar rats post-myocardial infarction (MI). Rats in one group were SHAM-operated and in the other group were subjected to MI surgery. One week after surgery, the MI group animals either received T3 and T4 hormones by gavage or underwent a low intensity aerobic exercise training protocol on a treadmill, and both treatments lasted until 10 weeks after MI. Untreated SHAM-operated and MI groups were also followed for the same duration. The cardiac function was assessed by echocardiography and catheterization, followed by blood collection (to measure T3, T4, and TSH hormones), and euthanasia. The lung, liver, heart, and tibia were collected (to assess hypertrophy and congestion indices). The left ventricle homogenate (without a scar) was used for the analyses of calcium handling proteins. Results showed that enhanced cardiac function was promoted by both interventions, with infarct size reduction, increased ejection fraction, and diastolic posterior wall thickness, but no alterations in heart rate, cardiac output, or T3, T4, and TSH levels. There was a positive force-frequency relationship accompanied by increased α-MHC, as well as decreased HSP70 protein expression. In conclusion, the effects of T3 and T4 hormone treatments were similar, and in some parameters superior, to those provided by the aerobic exercise training. Thus, lower doses of thyroid hormones could be more suitable as a coadjuvant treatment after MI, as a plausible alternative for patients who are intolerant to aerobic exercise training.

Effects of thyroid hormones on aortic tissue after myocardial infarction in rats.

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.

Thyroid hormones effects on oxidative stress and cardiac remodeling in the right ventricle of infarcted rats.

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.

Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction.

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.

T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats.

UNLABELLED: Myocardial infarction leads to a reduction in nitric oxide (NO) bioavailability and an increase in reactive oxygen species (ROS) levels. This scenario has been shown to be detrimental to the heart. Recent studies have shown that thyroid hormone (TH) administration presents positive effects after ischaemic injury. Based on this, the aim of this study was to evaluate the effect of TH on NO bioavailability as well as on endothelial nitric oxide synthase (eNOS) expression after myocardial infarction. Male Wistar rats were divided into three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). During 26 days, the AMIT group received T3 and T4 (2 and 8 µg/100 g/day, respectively) by gavage, while SHAM and AMI rats received saline. After this, the rats underwent echocardiographic analysis were sacrificed, and the left ventricle was collected for biochemical and molecular analysis. STATISTICAL ANALYSIS: one-way ANOVA with Student-Newman-Keuls post test. AMI rats presented a 38% increase in ROS levels. TH administration prevented these alterations in AMIT rats. The AMIT group presented an increase in eNOS expression, in NOS activity and in nitrite levels. TH administration also increased PGC-1α expression in the AMIT group. In conclusion, TH effects seem to involve a modulation of eNOS expression and an improvement in NO bioavailability in the infarcted heart.

Aerobic Exercise Promotes a Decrease in Right Ventricle Apoptotic Proteins in Experimental Cor Pulmonale.

Pulmonary arterial hypertension is characterized by progressive increases in resistance and pressure in the pulmonary artery and Cor pulmonale. The effect of exercise on hydrogen peroxide-dependent signaling in the right ventricle (RV) of Cor pulmonale rats was analyzed. Rats were divided into sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM) groups. Rats underwent exercise training (60% of VO2 max) for 5 weeks, with 3 weeks after monocrotaline injection (60 mg/kg intraperitoneally). Pulmonary resistance was enhanced in SM (2.0-fold) compared with SC. Pulmonary artery pressure was increased in SM (2.7-fold) and TM (2.6-fold) compared with their respective controls (SC and TC). RV hypertrophy indexes increased in SM compared with SC. Hydrogen peroxide was higher in SM (1.7-fold) than SC and was reduced by 47% in TM compared with SM. p-Akt was increased in TM (2.98-fold) compared with SM. The Bax/Bcl-2 ratio and caspase 3 were also increased (2.9-fold and 3.9-fold, respectively) in SM compared with SC. Caspase 3 was decreased in TM compared with SM (P < 0.05). Therefore, exercise training promoted a beneficial response by decreasing hydrogen peroxide concentrations, and consequently, apoptotic signaling in RV.

Cardioprotective effects of thyroid hormones in a rat model of myocardial infarction are associated with oxidative stress reduction.

Reactive oxygen species (ROS) are involved with progression from infarction to heart failure. Studies show that thyroid hormones (TH) present cardioprotective effects. This study aims to evaluate whether TH effects after infarction are associated to redox balance modulation. Male Wistar rats were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated+TH (SHAMT), and infarcted+TH (AMIT). During 26 days, animals received T3 (2 µg/100g/day) and T4 (8 µg/100g/day) by gavage. Echocardiographic parameters were assessed and heart tissue was collected to biochemical analysis. AMIT rats presented absence of lung congestion, less cardiac dilatation, and normalization in myocardial performance index, compared with AMI. AMI rats presented an increase in hydrogen peroxide levels and in lipid peroxidation and a decrease in GSH/GSSG. TH prevented these alterations in AMIT. In conclusion, TH seem to reduce the levels of ROS, preventing oxidative stress, and improving cardiac function in infarcted rats.

Effects of exercise on monocrotaline-induced changes in right heart function and pulmonary artery remodeling in rats.

Pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) is an experimental protocol of right heart failure. We analyzed the role of exercise training on the right ventricle structure and function, pulmonary artery remodeling, and GSK-3ß expression. Rats were divided among the following groups: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM). Rats underwent exercise training for a period of 5 weeks, with 3 weeks post-MCT injection. Rats in the SM and TM groups presented with an increase in right ventricle hypertrophy indexes and lung congestion. The right ventricular end diastolic pressure (RVEDP), right ventricular systolic pressure (RVSP), and its minimum and maximal pressure derivates were increased in the SM and TM groups. The right ventricle interstitial volume pulmonary artery thickness and p-GSK-3ß/GSK-3ß were increased in the MCT groups as compared with the control groups. The TM group had a reduction in interstitial volume, p-GSK-3ß/GSK-3ß ratio, pulmonary artery thickness, RVEDP, and an increase in intramyocardial vessels volume as compared with the SM group. The overall results have shown that the exercise protocol used promoted positive changes in right ventricle and pulmonary artery remodeling. These observations also suggest that structural remodeling may be influenced by signaling proteins, such as GSK-3ß.