Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury.

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κß, TNFα and IL-1ß expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.

Vascular Response of Triiodothyronine on Isolated Aortic Rings: Contribution of Redox Mechanisms. / Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox.

BACKGROUND: Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling. OBJECTIVE: Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms. METHODS: Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%. RESULTS: T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates. CONCLUSION: T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.

FUNDAMENTO: A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva ("redox"), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. OBJETIVOS: Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. MÉTODOS: Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. RESULTADOS: A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. CONCLUSÃO: A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.

Effects of Pterostilbene on Heart and Lung Oxidative Stress Parameters in 2 Experimental Models of Cardiovascular Disease: Myocardial Infarction and Pulmonary Arterial Hypertension.

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.

Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox / Vascular Response of Triiodothyronine on Isolated Aortic Rings: Contribution of Redox Mechanisms

Resumo Fundamento A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva ("redox"), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. Objetivos Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. Métodos Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. Resultados A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. Conclusão A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.

Abstract Background Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling. Objective Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms. Methods Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%. Results T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates. Conclusion T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.

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.

Effect of free and nanoemulsified ß-caryophyllene on monocrotaline-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), right ventricular (RV) failure and premature death. Compounds with vasodilatory characteristics, such as ß-caryophyllene, could be promising therapeutics for PAH. This study aimed to determine the effects of free and nanoemulsified ß-caryophyllene in lung oxidative stress and heart function in PAH rats. Male Wistar rats (170 g, n = 6/group) were divided into four groups: control (CO), monocrotaline (MCT), monocrotaline + ß-caryophyllene (MCT-Bcar) and monocrotaline + nanoemulsion with ß-caryophyllene (MCT-Nano). PAH was induced by MCT (60 mg/kg i.p.), and 7 days later, treatment with ß-caryophyllene, either free or in a nanoemulsion (by gavage, 176 mg/kg/day) or vehicle was given for 14 days. Echocardiographic and hemodynamic measurements were performed, and after, the RV was collected for morphometry and the lungs for evaluation of oxidative stress, antioxidant enzymes, total sulfhydryl compounds, nitric oxide synthase (NOS) activity and endothelin-1 receptor expression. RV hypertrophy, increased PVR and RV systolic and diastolic pressures (RVSP and RVEDP, respectively) and increased mean pulmonary arterial pressure (mPAP) were observed in the MCT group. Treatment with both free and nanoemulsified ß-caryophyllene reduced RV hypertrophy, mPAP, RVSP and lipid peroxidation. The reduction in RVSP was more pronounced in the MCT-Nano group. Moreover, RVEDP decreased only in the MCT-Nano group. These treatments also increased superoxide dismutase, catalase and NOS activities and decreased endothelin-1 receptors expression. Both ß-caryophyllene formulations improved mPAP, PVR and oxidative stress parameters. However, ß-caryophyllene in a nanoemulsion was more effective in attenuating the effects of PAH.

The Effect of Telerehabilitation on Physical Fitness and Depression/Anxiety in Post-COVID-19 Patients: A Randomized Controlled Trial.

Aim: The aim of this research was to evaluate the impact of a telerehabilitation program on physical fitness, muscle strength, and levels of depression and anxiety in post-COVID-19 patients. Methods: Thirty-two individuals recovered from COVID-19 (48.20±12.82 years) were allocated into either a telerehabilitation (TG n=16) or control (CG n=16) group. Physical fitness, handgrip strength, depression and anxiety levels were assessed before and after an 8-week intervention. Results: There was a significant improvement in muscle strength in both groups. Physical fitness significantly increased compared to the CG at the end of the intervention. Levels of anxiety and depression significantly decreased after the intervention when compared to the CG. Conclusion: Eight weeks of functional telerehabilitation training is a viable and efficient way to rehabilitate patients affected by COVID-19, as it improved physical conditioning and mental health.

Circulating Total Extracellular Vesicles Cargo Are Associated with Age-Related Oxidative Stress and Susceptibility to Cardiovascular Diseases: Exploratory Results from Microarray Data.

Aging is a risk factor for many non-communicable diseases such as cardiovascular and neurodegenerative diseases. Extracellular vesicles and particles (EVP) carry microRNAs that may play a role in age-related diseases and may induce oxidative stress. We hypothesized that aging could impact EVP miRNA and impair redox homeostasis, contributing to chronic age-related diseases. Our aims were to investigate the microRNA profiles of circulating total EVPs from aged and young adult animals and to evaluate the pro- and antioxidant machinery in circulating total EVPs. Plasma from 3- and 21-month-old male Wistar rats were collected, and total EVPs were isolated. MicroRNA isolation and microarray expression analysis were performed on EVPs to determine the predicted regulation of targeted mRNAs. Thirty-one mature microRNAs in circulating EVPs were impacted by age and were predicted to target molecules in canonical pathways directly related to cardiovascular diseases and oxidative status. Circulating total EVPs from aged rats had significantly higher NADPH oxidase levels and myeloperoxidase activity, whereas catalase activity was significantly reduced in EVPs from aged animals. Our data shows that circulating total EVP cargo-specifically microRNAs and oxidative enzymes-are involved in redox imbalance in the aging process and can potentially drive cardiovascular aging and, consequently, cardiac disease.

Copaiba oil improves pulmonary nitric oxide bioavailability in monocrotaline-treated rats.

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.

Simultaneous voltammetric determination of 7-methyl-guanine and 5-methyl-cytosine using a cathodically pre-treated boron-doped diamond electrode.

Given the importance of identifying the presence of biomarkers of human diseases in DNA samples, the main objective of this work was to investigate, for the first time, the electro-catalytic oxidation of 7-methyl-guanine (7-mGua) and 5-methyl-cytosine (5-mCyt) on a boron doped diamond electrode pre-treated cathodically (red-BDDE), using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). The anodic peak potentials of 7-mGua and 5-mCyt by DPV were at E = 1.04 V and E = 1.37 V at pH = 4.5, indicating excellent peak separation of approximately 330 mV between species. Using DPV, experimental conditions such as supporting electrolyte, pH and influence of interferents were also investigated to develop a sensitive and selective method for individual and simultaneous quantification of these biomarkers. The analytical curves for the simultaneous quantification of 7-mGua and 5-mCyt in the acid medium (pH = 4.5) were: concentration range of 0.50-5.00 µmol L-1 (r = 0.999), detection limit of 0.27 µmol L-1 for 7-mGua; from 3.00 to 25.00 µmol L-1 (r = 0.998), with a detection limit of 1.69 µmol L-1 for 5-mCyt. A new DP voltammetric method for the simultaneous detection and quantification of biomarkers 7-mGua and 5-mCyt using a red-BDDE is proposed.

COVID-19 vaccination challenges: from fake news to vaccine hesitancy. / Desafios da imunização contra COVID-19 na saúde pública: das fake news à hesitação vacinal.

This article aims to synthesize articles addressing fake news and COVID-19 vaccine hesitancy in the context of public health. We conducted an integrative review of articles published in any language between 2019 and 2022 in journals indexed in the following databases: Latin American and the Caribbean Literature on Health Sciences, Medical Literature Analysis and Retrieval System Online, Scopus, Web of Science, and Embase. A critical analysis was performed, guided by the research question and objective of the review. Eleven articles were selected, the overwhelming majority of which were cross-sectional studies. The main factors related to vaccine take-up highlighted by the studies were gender, age, education level, political leanings, religion, trust in health authorities, and perceptions of side-effects and vaccine efficacy. The main obstacles to attaining optimal vaccination coverage were vaccine hesitancy and disinformation. All studies addressed the relationship between low vaccination intention and the use of social media as a source of information about SARS-CoV-2. It is necessary to build public trust in vaccine safety and efficacy. Promoting a better understanding of the benefits of COVID-19 vaccination is essential to combat vaccine hesitancy and improve vaccine take-up.

O objetivo deste artigo é sintetizar artigos que abordam fake news e hesitação vacinal contra a COVID-19 no contexto de saúde pública. Revisão integrativa que incluiu estudos originais indexados nas bases de dados Literatura Latino Americana e do Caribe em Ciências da Saúde; Medical Literature Analysis and Retrieval System Online; Scopus; Web of Science e Embase, publicados em qualquer idioma, entre 2019 e 2022. A análise crítica foi realizada na forma descritiva, consoante à pergunta de pesquisa e ao objetivo da revisão. Foram selecionados 11 artigos, com predomínio de estudos transversais. Relacionaram-se ao processo de adesão à vacinação: gênero, idade, estado civil, escolaridade, posicionamento político, religião, confiança em autoridades de saúde, percepção de efeitos colaterais e eficácia das vacinas, entre outros. Hesitação e desinformação são os principais entraves para se alcançar a cobertura vacinal em muitos países. Todos os estudos abordam a relação entre baixa intenção de imunização e uso de mídias sociais como fonte de informação sobre o SARS-CoV-2. É necessário aumentar a confiança na segurança e eficácia das vacinas. A melhor compreensão dos benefícios da vacinação para COVID-19 é imprescindível para combater a hesitação e ampliar a adesão vacinal.

Desafios da imunização contra COVID-19 na saúde pública: das fake news à hesitação vacinal / COVID-19 vaccination challenges: from fake news to vaccine hesitancy

Resumo O objetivo deste artigo é sintetizar artigos que abordam fake news e hesitação vacinal contra a COVID-19 no contexto de saúde pública. Revisão integrativa que incluiu estudos originais indexados nas bases de dados Literatura Latino Americana e do Caribe em Ciências da Saúde; Medical Literature Analysis and Retrieval System Online; Scopus; Web of Science e Embase, publicados em qualquer idioma, entre 2019 e 2022. A análise crítica foi realizada na forma descritiva, consoante à pergunta de pesquisa e ao objetivo da revisão. Foram selecionados 11 artigos, com predomínio de estudos transversais. Relacionaram-se ao processo de adesão à vacinação: gênero, idade, estado civil, escolaridade, posicionamento político, religião, confiança em autoridades de saúde, percepção de efeitos colaterais e eficácia das vacinas, entre outros. Hesitação e desinformação são os principais entraves para se alcançar a cobertura vacinal em muitos países. Todos os estudos abordam a relação entre baixa intenção de imunização e uso de mídias sociais como fonte de informação sobre o SARS-CoV-2. É necessário aumentar a confiança na segurança e eficácia das vacinas. A melhor compreensão dos benefícios da vacinação para COVID-19 é imprescindível para combater a hesitação e ampliar a adesão vacinal.

Abstract This article aims to synthesize articles addressing fake news and COVID-19 vaccine hesitancy in the context of public health. We conducted an integrative review of articles published in any language between 2019 and 2022 in journals indexed in the following databases: Latin American and the Caribbean Literature on Health Sciences, Medical Literature Analysis and Retrieval System Online, Scopus, Web of Science, and Embase. A critical analysis was performed, guided by the research question and objective of the review. Eleven articles were selected, the overwhelming majority of which were cross-sectional studies. The main factors related to vaccine take-up highlighted by the studies were gender, age, education level, political leanings, religion, trust in health authorities, and perceptions of side-effects and vaccine efficacy. The main obstacles to attaining optimal vaccination coverage were vaccine hesitancy and disinformation. All studies addressed the relationship between low vaccination intention and the use of social media as a source of information about SARS-CoV-2. It is necessary to build public trust in vaccine safety and efficacy. Promoting a better understanding of the benefits of COVID-19 vaccination is essential to combat vaccine hesitancy and improve vaccine take-up.

The challenge of improving pterostilbene (PTS) solubility for solid and semi-solid dosage forms: The obtention of binary and ternary systems.

Pterostilbene (PTS) is a drug candidate with low water solubility and poor bioavailability. On the other hand, drug:cyclodextrins complexes frequently provide bulk powders with low drug concentrations, which is crucial for obtention solid or semi-solid pharmaceutical dosage forms. In order to determine the optimal conditions for enhancing the solubility of PTS:BCD (ß-cyclodextrin) complex, a Box-Behnken design was performed. Although the optimal conditions have been applied, low complexation efficiency (0.127) and the bulk powder remained. A PTS:BCD:HPMC (HPMC, hydroxypropyl methylcellulose) ternary system was developed to overcome this limitation, comparing two media, water and a mixture of ethanol-water. When ethanol was used as a co-solvent, the PTS:BCD:HPMC ternary system (freeze-dried) contained 116.65 ± 1.40 mg/g of PTS. This value was 3.4-fold higher than the PTS content observed when the same ternary system was obtained in aqueous media (34.8 mg/g) and 2.8-fold higher than the PTS content observed for PTS:BCD complex (freeze-dried) obtained using ethanol as a co-solvent. Dissolution tests revealed that after 120 min, in a buffer with a pH value of 1.2, only 43% of PTS dissolved. In contrast, 80% and 90% of PTS were dissolved from the PTS:BCD complex and PTS:BCD:HPMC ternary system, respectively. Moreover, the dissolution was fast in a buffer with a pH value of 6.8. PTS:BCD complex reached the maximum PTS dissolution at 75 min and PTS:BCD:HPMC at 45 min. In summary, the results of this study demonstrated, for the first time, that low-bulk powders with a high content of PTS can be obtained from PTS:BCD:HPMC ternary systems using ethanol as a co-solvent. This new finding offers a valuable alternative for producing solid or semi-solid formulations containing highly soluble PTS.

Influence of carvedilol and thyroid hormones on inflammatory proteins and cardioprotective factor HIF-1α in the infarcted heart.

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.

Pleurotus albidus (Agaricomycetes) Antioxidant Action Induces Vasodilation in Aorta Arteries: The Influence of the NADPH/NOS Balance.

The main objective of this work was to evaluate whether Pleurotus albidus extract exerts influences on aorta artery tone by its antioxidant properties. The hearts and aortic arteries of male Wistar rats were removed for use in biochemical analysis and vascular reactivity. Both tissues were exposed to P. albidus extract at different concentrations for 30 min and were then exposed to a free radical generation system for 30 min. The extract reduced lipid peroxidation levels and increased catalase and glutathione peroxidase activity in cardiac tissue. In the aorta, P. albidus extract demonstrated a direct vasodilatory effect, which was associated with a reduction in nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity and an increase in sulfhydryl levels and nitric oxide synthase (NOS) activity. Our findings suggest that P. albidus extract has regulatory potential on aorta arteries, regulating the balance of NOX/NOS enzymes and then influencing vessel tone. Further studies are needed to determine the protective mechanisms of the extract.

Gestational purple grape juice consumption does not change fetal ductus arteriosus constriction in Wistar rats.

Grape juice consumption may influence the early occurrence of ductal constriction during pregnancy, since the consumption of foods rich in polyphenols can be linked to the premature constriction of the ductus arteriosus. This study aimed to evaluate the effect of purple grape juice consumption during gestation on fetal ductus arteriosus closure, prostaglandin levels, and oxidative stress markers in Wistar rats. We divided 18 pregnant rats into four groups: a control group (C), a single-dose grape juice group (SDGJ), a two-dose grape juice group (TDGJ) of 7 µl/g body weight per day, and an indomethacin group (I). Blood was collected on gestational day (GD) 0, 14, and 20. Prostaglandin levels were measured, and the livers and hearts were removed from the mothers and fetuses for oxidative stress analysis; histology of the fetal ductus arteriosus was performed. Prostaglandin levels (pg/ml) at GD 20 were (C:1462.10 ± 314.61); (SDGJ:987.66 ± 86.25); (TDGJ:1290.00 ± 221.57), and (I:584.75 ± 46.77). Fetal ductus arteriosus closure occurred only in the indomethacin group. Lipid peroxidation evaluated through thiobarbituric acid reactive substances (nmol/mg protein) in maternal livers was lower in the grape juice groups (C: 4.11 ± 0.76 nmol/mg protein), (SDGJ: 2.34 ± 0.36), (TDGJ: 1.52 ± 0.18), and (I: 4.20 ± 0.76). Sulfhydryls (nmol/mg protein) were lower in the TDGJ group (C:763.59 ± 61.38 nmol/mg protein), (SDGJ:978.88 ± 158.81), (TDGJ:385.32 ± 86.78), and (I:727.72 ± 49.12). Also, superoxide dismutase activity (USOD/mg protein) was higher in fetal hearts in this group: (C:5.29 ± 0.33), (SDGJ:4.48 ± 0.47), (TDGJ:7.35 ± 0.43), and (I:6.00 ± 0.18). We conclude that grape juice consumption in pregnancy does not induce ductus arteriosus closure in the fetus and presented potential antioxidant effects.

Antioxidant system disturbances and mitochondrial dysfunction induced by 3-methyglutaric acid in rat heart are prevented by bezafibrate.

Barth syndrome (BTHS) and dilated cardiomyopathy with ataxia syndrome (DCMA) are biochemically characterized by high levels of 3-methylglutaric acid (MGA) in the urine and plasma of affected patients. Although cardiolipin abnormalities have been observed in these disorders, their pathophysiology is not fully established. We evaluated the effects of MGA administration on redox homeostasis and mitochondrial function in heart, as well as on vascular reactivity in aorta of Wistar rats without cardiolipin genetic deficiency. Potential cardioprotective effects of a pretreatment with bezafibrate (BEZ), a pan-PPAR agonist that induces mitochondrial biogenesis, were also determined. Our findings showed that MGA induced lipid peroxidation, altered enzymatic and non-enzymatic antioxidant defenses and reduced respiratory chain function in rat heart. MGA also increased Drp1 and reduced MFN1 levels, suggesting mitochondrial fission induction. Moreover, MGA altered MAPK and Akt signaling pathways, and had a strong tendency to reduce Sirt1 and PGC-1α, indicative of mitochondrial biogenesis impairment. Aorta vascular reactivity was further altered by MGA. Additionally, BEZ mitigated most alterations on antioxidant defenses and mitochondrial quality control proteins provoked by MGA. However, vascular reactivity disturbances were not prevented. It may be presumed that oxidative stress, mitochondrial bioenergetics and control quality disturbances, and vascular reactivity impairment caused by MGA may be involved in the cardiac failure observed in BTHS and DCMA, and that BEZ should be considered as a pharmacological candidate for the treatment of these disorders.

Pterostilbene Reduces Experimental Myocardial Infarction-Induced Oxidative Stress in Lung and Right Ventricle. / Pterostilbeno Reduz o Estresse Oxidativo no Pulmão e no Ventrículo Direito Induzido por Infarto do Miocárdio Experimental.

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.

Sulforaphane Effects on Cardiac Function and Calcium-Handling-Related Proteins in 2 Experimental Models of Heart Disease: Ischemia-Reperfusion and Infarction.

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.

Blueberry extract attenuates norepinephrine-induced oxidative stress and apoptosis in H9c2 cardiac cells.

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.