Blueberry extract decreases oxidative stress and improves functional parameters in lungs from rats with pulmonary arterial hypertension.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a condition characterized by an increased resistance of pulmonary vasculature, culminating in an increase in pulmonary pressure. This process involves disturbances in lung redox homeostasis, causing progressive right heart failure. In this context, the use of natural antioxidants, such as those found in blueberries, may represent a therapeutic approach. The aim of this study was to evaluate the effect of blueberry extract (BB) on functional parameters and oxidative stress levels in rat lungs with induced PAH. METHODS: Forty-eight male Wistar rats (weighing 200 ± 20 g) were randomized into five groups: control, monocrotaline, monocrotaline + BB 50, monocrotaline + BB 100, and monocrotaline + BB 200. PAH was induced by the administration of monocrotaline (60 mg/kg, intraperitoneal). Rats were treated with BB at doses of 50, 100, and 200 mg/kg via gavage for 5 wk (2 wk before monocrotaline and 3 wk after monocrotaline injection). At day 35, rats were submitted to echocardiography and catheterization. They were then sacrificed and lungs were harvested for biochemical analyses. RESULTS: BB increased the E/A ratio of blood flow across the tricuspid valve and tricuspid annular phase systolic excursion, as wells as decreased the mean pulmonary artery pressure of animals compared with the PAH group. Moreover, BB decreased total reactive species concentration and lipid oxidation, reduced activity of nicotinamide adenine dinucleotide phosphate oxidase and expression of xanthine oxidase, increased the activity of superoxide dismutase and restored sulfhydryl content in the animal lungs compared with those in the PAH group. Additionally, BB restored expression of the antioxidant transcriptional factor Nrf2 in the lungs of the animal subjects. Finally, BB normalized the endothelin receptor (ETA/ETB) expression ratio in the animal lungs, which were increased in the PAH group. CONCLUSION: Intervention with BB mitigated functional PAH outcomes through improvement of the pulmonary redox state. Our results provide a basis for future research on natural antioxidant interventions as a novel treatment strategy in PAH.

Carvedilol and thyroid hormones co-administration mitigates oxidative stress and improves cardiac function after acute myocardial infarction.

After acute myocardial infarction (AMI), reactive oxygen species and oxidative stress have important roles in the progression to heart failure. As a therapeutic alternative, thyroid hormones (TH) revealed cardioprotective effects after AMI, including decreasing oxidative stress. Carvedilol beta-blocker, already used in the clinical treatment of AMI, also mitigate cardiac pathological remodelling. This study assessed the effects of post-AMI carvedilol and TH co-administration on oxidative stress and cardiac function as well as whether those effects were synergistic. Male Wistar rats were divided into five groups: sham-operated (SHAM), infarcted (MI), infarcted + TH (MI + TH), infarcted + carvedilol (MI + C) and infarcted + C + TH (MI + C + TH). Two days post-surgery, the SHAM and MI groups received saline, and treated groups received their respective treatments by gavage for 12 days. The animals were submitted to echocardiographic evaluation, ventricular catheterization and euthanized for heart collection to perform oxidative stress analysis. Treated groups improved for ejection fraction compared to the MI group. Carvedilol decreased the positive chronotropic TH effects in the MI + C + TH group. The MI and MI + C groups had increased reactive oxygen species and reduced sulfhydryl levels. Carvedilol and TH co-administration showed synergic effects in the MI + C + TH group, reducing reactive oxygen species levels and improving GSH/GSSG ratio. Moreover, co-treatment attenuated NADPH oxidase activity in the MI group. Therefore, this study showed for the first time that carvedilol and TH co-administration may improve redox balance and cardiac function after AMI. Such co-administration could represent a therapeutic strategy capable of preventing cardiac dysfunction and redox unbalance after AMI.