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This study explored the effect of pterostilbene (PTS) complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on right heart function, glutathione and glutaredoxin systems, and the expression of redox-sensitive proteins involved with regulation calcium levels in the experimental model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). After 7 days of PAH induction, rats received daily doses of the PTS:HPβCD complex (corresponding to 25, 50, or 100 mg·kg−1of PTS) or vehicle (control group, CTR0) (an aqueous solution containing HPβCD; CTR0 and MCT0 (MCT group that did not receive PTS treatment)) via oral administration for 2 weeks. The results showed that the PTS:HPβCD complex increased the content of reduced glutathione and the activity of glutathione-S-transferase and glutaredoxin in the right ventricle (RV) of MCT-treated rats in a dose-dependent manner. Additionally, at higher doses, it also prevented the reduction of stroke volume and cardiac output, prevented myocardial performance index (MPI) increase, reduced lipoperoxidation, reduced total phospholamban, and increased the expression of sarcoplasmic reticulum calcium ATPase in the RV of MCT-treated rats. These results demonstrate that the PTS:HPβCD complex has a dose-dependent antioxidant mechanism that results in improved cardiac function in experimental right heart failure. Our results open a field of possibilities to PTS administration as new therapeutic approach to conventional therapy for right ventricular dysfunction.Novelty Pterostilbene complexed with hydroxypropyl-β-cyclodextrin could be a new therapeutic approach. Pterostilbene complexed with hydroxypropyl-β-cyclodextrin reestablishes redox homeostasis through glutathione metabolism modulation, leading to an improved MPI in pulmonary arterial hypertension-provoked right heart failure.

Pterostilbene is a natural constituent with numerous preventive and therapeutic properties used for treating a wide range of human diseases. It has been isolated from blueberries in high concentrations. A versatile specific-stability indicating liquid chromatography method for reliable quantitative determination of pterostilbene in blueberry extracts was developed. In the stability-indicating analysis, pterostilbene samples were exposed to stress conditions: temperature, UV light, and oxidative, acid and alkaline media. The robustness of the method was evaluated using a Box-Behnken experimental design. Pterostilbene was stable in acid and alkaline media, but unstable when exposed to oxidation, high temperature, and UV light. Using the proposed method, it was demonstrated that degradation products did not interfere in the analyte analysis. The method revealed to be simple, fast, selective, linear, precise and accurate for the quantitative analysis of pterostilbene in Vaccinium myrtillus extract. Besides being a specific-stability indicating method, it demonstrated to be applicable to quantify pterostilbene in pterostilbene:β-cyclodextrin complexes and pterostilbene:β-cyclodextrin:hydrophilic polymer ternary systems. These findings are relevant for the development of food, pharmaceutical or cosmetic products containing pterostilbene or blueberry extracts.

This study was designed to investigate the effect of pterostilbene (PTS) on cardiac oxidative stress in vitro, as this is a simple and promising methodology to study cardiac disease. Cardiac myoblasts (H9c2 cells) and homogenised cardiac tissue were incubated with the PTS and cyclodextrin (PTS ? HPbCD) complex for 1 and 24 h, respectively, at concentrations of 50 lM for the cells and 25 and 50 lM for cardiac tissue. The PTS ? HPbCD complex was used to increase the solubility of PTS in water. After the pretreatment period, cardiomyoblasts were challenged with hydrogen peroxide (6.67 lM) for 10 min, while cardiac tissue was submitted to a hydroxyl radical generator system (30 min). Cellular viability, oxidative stress biomarkers (e.g. total reactive oxygen species (ROS), carbonyl assay and lipoperoxidation) and the antioxidant response (e.g. sulfhydryl and the antioxidant enzyme activities of superoxide dismutase, catalase and glutathione peroxidase) were evaluated. In cardiomyoblasts, the PTS ? HPbCD complex (50 lM) increased cellular viability. Moreover, the PTS ? HPbCD complex also significantly increased sulfhydryl levels in the cells submitted to an oxidative challenge. In cardiac tissue, lipid peroxidation, carbonyls and ROS levels were significantly increased in the groups submitted to oxidative damage, while the PTS ? HPbCD complex significantly reduced ROS levels in these groups. In addition, the PTS ? HPbCD complex also provoked increased catalase activity in both experimental protocols. These data suggest that the PTS ? HPbCD complex may play a cardioprotective role through a reduction of ROS levels associated with an improved antioxidant response.

The objectives of this study were to promote the aqueous solubility of pterostilbene (PTS) by complexation with hydroxypropyl-β-cyclodextrin (HPβCD), characterize the complex under physical aspects, to make its oral administration feasible in biological tests, and to investigate their pharmacological properties. For 14 days, rats received daily PTS:HPΒCD complex at doses of 25, 50, or 100 mg kg−1 per day orally. The results showed no kidney or liver damage, nor any induction of apoptosis by the administered doses. Also, the complex showed dose-dependent antioxidant effects in the rat liver, as evidenced by a reduction in lipid peroxidation and reactive oxygen species, as well as an increase in non-enzymatic antioxidant. PTS:HPΒCD complex also increased the expression of sensitive redox proteins such as AKT and GSK-3β related to the insulin signaling pathway in the liver. Thus, the complexation demonstrated to be able to increase the apparent solubility of PTS making feasible dose curve administration and could be a food alternative complementary to antioxidant therapeutic. Therefore, the PTS:HPβCD complex can be used for prevention of diseases related to oxidative damage and insulin signaling.

Background Pulmonary arterial hypertension is a disease characterized by increased pulmonary vascular resistance and redox imbalance, leading to failure of right ventricle. Trapidil has been described to improve the redox balance and cardiac conditions. Hypothesis Trapidil can improve the redox balance and contribute to functional improvements of the RV in PAH. Methods and Results Male, 5week-old Wistar rats were divided into four groups: Control, Control + Trapidil, Monocrotaline and Monocrotaline + Trapidil. PAH was induced by an intraperitoneal injection of monocrotaline 60 mg/kg at day 0. Treatment started at day 7 (5 or 8 mg/kg/day) until day 14, when animals were euthanized after echocardiography and catheterism. Right ventricular systolic pressure and pressure/time derivatives were increased in monocrotaline animals. The increased right ventricular diameters in monocrotaline groups were reduced with trapidil. Monocrotaline groups showed higher lipid peroxidation and glutathione peroxidase activity. Trapidil reduced NADPH oxidases activities and increased the reduced glutathiones/total glutathiones ratio. Protein expression of phospholamban in RV was diminished in monocrotaline groups, whereas expression of RyR and SERCA was enhanced in the groups treated with trapidil. Conclusion Our data suggest that trapidil induces an improvement in RV remodeling in PAH model, mitigating the progression of the disease.

Background and Purpose In cor pulmonale, the increased afterload imposed on the right ventricle (RV) generates a maladaptive response, impairing the contractile cardiac function. Oxidative mechanisms play an important role in the pathophysiology and progression of this disease. The administration of pterostilbene (PTS), a phyto-phenol with antioxidant potential, may represent a therapeutic alternative. In the present study, the objective was to evaluate the effect of PTS complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on hypertrophy, contractile function and oxidative parameters in the RV of rats with pulmonary hypertension induced by monocrotaline administration. Experimental Approach The rats received daily doses of PTS: HPβCD complex at 25, 50 or 100 mg kg-1 by oral administration for 14 days. The diastolic function (E/A ratio) and systolic function (FEC, FAC and TAPSE) of the RV were determined by echocardiography. Key Results Our findings suggest that PTS: HPβCD complex reduces NADPH oxidase-dependent superoxide anion concentration and oxidative stress in RV in a dose-dependent manner, resulting in prevention of maladaptative remodelling and protection of systolic function. Conclusion These cardioprotective mechanisms may be related, in part, to the antioxidant potential of PTS, favoured by the increased oral bioavailability promoted by the presence of HPβCD in the complex.

High-fat-diet (HFD) has been related to metabolic and cardiovascular diseases. Consumption of grapes and their byproducts containing phenolic compounds has been reported due to the benefits they produce for human health. The purpose of this study was to investigate the antioxidant and protective effect of chronic intake of purple grape juice on certain biochemical and physiological changes promoted by the consumption of HFD. Forty male rats were randomly divided into four groups to receive standard or HFD diet and/or conventional (CGJ) or organic grape juice (OGJ) for three months. Dietary intake, body weight gain, cardiometabolic parameters, and serum lipoperoxidation were investigated. Results showed that consumption of CGJ and OGJ changed the pattern of food and drink intake of the animals. There was a reduction in the body weight of animals that consumed grape juices and an increase in the weight gain in HFD and OGJ rats. HFD increased abdominal fat and the abdominal fat/weight ratio, and both grape juices prevented these modifications. HFD increased hepatic enzymes levels (aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT)) and reduced urea. Purple grape juices prevented some of these changes. HFD enhanced lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) in serum and CGJ and OGJ prevented this increase. The consumption of purple grape juice has the potential to prevent and ameliorate most of the alterations provoked by HFD, therefore regular intake of grape products could promote beneficial effects.

Oxidative stress alters signalling pathways for survival and cell death favouring the adverse remodelling of postmyocardial remnant cardiomyocytes, promoting functional impairment. The administration of pterostilbene (PTS), a phytophenol with antioxidant potential, can promote cardioprotection and represents a therapeutic alternative in acute myocardial infarction (AMI). The present study aims to explore the effects of oral administration of PTS complexed with hydroxypropyl-β-cyclodextrin HPβCD (PTS:HPβCD complex) on the glutathione cycle, thiol protein activities and signalling pathways involving the protein kinase B (AKT) and glycogen synthase kinase-3β (GSK-3β) proteins in the left ventricle (LV) of infarcted rats. Animals were submitted to acute myocardial infarction through surgical ligation of the descending anterior branch of the left coronary artery and received over 8 days, by gavage, PTS:HPβCD complex at dose of 100 mg kg

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.

Organochalcogens are extensively produced and employed by industry and agriculture, and the risk of occupational and environmental toxicity to them has been poorly understood. Here, we investigated the acute effect of a new organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on biochemical and hematological parameters in male Wistar rats. The animals were treated with a single intraperitoneal injection of the organochalcogen at doses of 125, 250 or 500mgkg –1 . After 60min, the animals were sacrificed by decapitation, and the trunk blood was collected for determination of glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase, lactate dehydrogenase, urea, creatinine, C-reactive protein, red blood cells, hematocrit, hemoglobin and white blood cells (WBC). Our results showed a reduction in cholesterol levels in all treated groups, an increase in ALT activity at doses of 250 and 500mgkg –1 , a decrease of hemoglobin and an increase in WBC in animals that received 250 and 500mgkg –1 of the organoselenium. In addition, we observed an increase in neutrophil counts at 125mgkg –1 dose and a decrease at 500mgkg –1 dose. We also verified an increase in lymphocyte counts at the dose of 500mgkg –1 . Thus, the present study shows that the acute treatment with this new organochalcogen causes biochemical changes

Serra Gaucha is described as the most important wine region of Brazil. Regarding cultivars widespread in the Serra Gaucha, about 90 % of the area is occupied by vines of Vitis labrusca that is the most important specie used in grape juice production. The objective of this study was to investigate the antioxidant and neuroprotective effect of chronic intake of purple grape juice (organic and conventional) from Bordo variety (V. labrusca) on oxidative stress in different brain regions of rats supplemented with high-fat diet (HFD) for 3 months. A total of 40 male rats were randomly divided into 4 groups. Group 1 received a standard diet and water, group 2 HFD and water, group 3 HFD and conventional grape juice (CGJ), and group 4 HFD and organic grape juice (OGJ). All groups had free access to food and drink and after 3 months of treatment the rats were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum isolated and homogenized on ice for oxidative stress analysis. We observed that the consumption of calories in HFD and control groups, were higher than the groups supplemented with HFD and grape juices and that HFD diet group gain more weight than the other animals. Our results also demonstrated that HDF enhanced lipid peroxidation (TBARS) and protein damage (carbonyl) in cerebral cortex and hippocampus, reduced the non-enzymatic antioxidants defenses (sulfhydryl) in cerebral cortex and cerebellum, reduced catalase and superoxide dismutase activities in all brain tissues and enhanced nitric oxide production in all cerebral tissues. CGJ and OGJ were able to ameliorate these oxidative alterations, being OGJ more effective in this protection. Therefore, grape juices could be useful in the treatment of some neurodegenerative diseases associated with oxidative damage.

The aim of this study was to evaluate the effect of chronic treatment with the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some behavioral and biochemical parameters in the brain, liver, kidney and serum of 90-day-old male Wistar rats. The animals received the organoselenium at doses of 125, 250 or 500 μg/kg body weight intraperitoneally once daily for 30 days. Results showed that chronic treatment with this compound induced behavioral changes in animals, such as increasing of rearing at dose of 250 μg/kg and increasing of ambulation in all concentrations tested. On the other hand, we did not observe any alterations in the body weight gain of the animals. Moreover, the activity of the enzyme creatine kinase (CK) decreased in the cerebral cortex, cerebellum and kidney and increased in the liver after the chronic treatment with the organoselenium compound at dose of 500 μg/kg. The compound also increased aspartate aminotransferase (AST) and urea levels in serum of rats at 500 μg/kg. Glucose, cholesterol, triglycerides, creatinine, alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels were not changed by the treatment. Our results thus show that chronic administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one is able to significantly change the activity of CK in Wistar rats, resulting in a change in cellular energy homeostasis in these tissues, liver damage and behavioral changes in the animals studied.