Denise dos Santos Lacerda

Hepatoprotective and Antioxidant Potential of Organic and Conventional Grape Juices in Rats Fed a High-Fat Diet.

The objective of this study was to investigate the antioxidant and hepatoprotective effect of the chronic use of conventional (CGJ) or organic (OGJ) grape juice from the Bordeaux variety grape on oxidative stress and cytoarchitecture in the liver of rats supplemented with a high-fat diet (HFD) for three months. The results demonstrated that HFD induced an increase in thiobarbituric acid-reactive substances (TBARS), catalase (CAT) activity and 2′,7′-dihydrodichlorofluorescein (DCFH) oxidation and a decrease in sulfhydryl content and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. HFD also induced hepatocellular degeneration and steatosis. These alterations were prevented by CGJ and OGJ, where OGJ was more effective. Therefore, it was concluded that HFD induced oxidative stress and liver damage and that the chronic use of grape juice was able to prevent these alterations.

Pterostilbene reduces oxidative stress, prevents hypertrophy and preserves systolic function of right ventricle in cor pulmonale model

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 phytophenol with antioxidant potential, may represent a therapeutic option. In the present study, we evaluated 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 the administration of monocrotaline (MCT).

Acute administration of the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces biochemical and hematological disorders in male rats

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 500 µg·kg–1. After 60 min, 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 500 µg·kg–1, a decrease of hemoglobin and an increase in WBC in animals that received 250 and 500 µg·kg–1 of the organoselenium. In addition, we observed an increase in neutrophil counts at 125 µg·kg–1 dose and a decrease at 500 µg·kg–1 dose. We also verified an increase in lymphocyte counts at the dose of 500 µg·kg–1. Thus, the present study shows that the acute treatment with this new organochalcogen causes biochemical changes and hematological disorders in male rats. Copyright

Antioxidant and hepatoprotective effects of an organic grapevine leaf (Vitis labrusca L.) extract in diabetic rats

Our objective was to investigate the antioxidant effect of an aqueous extract of organic grapevine leaves (Vitis labrusca L.) on the livers of diabetic rats and to evaluate the resulting changes in metabolic and biochemical parameters. Diabetic rats received daily intragastric doses of 50, 100 or 200 mg kg−1 of the grapevine extract for 30 days. Grapevine leaf extract showed a dose-dependent antioxidant effect on the livers of diabetic rats, evidenced by decreases in TBARS and in carbonyl levels and increases in sulfhydryl levels. Moreover, the extract (200 mg kg−1) prevented weight loss and reduced LDL cholesterol (50 mg kg−1), urea (50 mg kg−1), and AST (50 and 100 mg kg−1) levels in diabetic rats at the indicated doses. Thus, we suggest that chronic treatment with an extract of grapevine leaves may represent an adjuvant therapy for the treatment and/or prevention of diabetic complications because of its antioxidant, hepatoprotective and possible hypolipidemic effects shown here.

Toxicological evaluation of chronic exposure to the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one in male rats

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.

Effect of pterostilbene complexed with cyclodextrin on rat liver: potential reduction of oxidative damage and modulation redox-sensitive proteins

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.

Stilbenoid pterostilbene complexed with cyclodextrin preserves left ventricular function after myocardial infarction in rats: possible involvement of thiol proteins and modulation of phosphorylated GSK-3β

Abstract 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−1 day−1 (AMI + PTS group) or vehicle (aqueous solution with HPβCD) divided into Sham-operated (SHAM) and infarcted (AMI) groups. The results showed that the PBS: HPβCD complex decreased lipid peroxidation, prevented the decrease in thioredoxin reductase (TRxR) activity, and increased the activity of glutathione-S-transferase (GST) and glutaredoxin (GRx). Additionally, the expression of nuclear factor-erythroid two (Nrf2) and p-GSK-3β was increased, whereas the p-GSK-3β/GSK-3β ratio was reduced in the LV of the infarcted animals. Overall, the PTS:HPβCD complex modulates activity of thiol-dependent enzymes and induces to the expression of antioxidant proteins, improving systolic function and mitigating the adverse cardiac remodelling post infarction.

Trapidil improves hemodynamic, echocardiographic and redox state parameters of right ventricle in monocrotaline-induced pulmonary arterial hypertension model

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.

Benefits of Vine Leaf on Different Biological Systems

For centuries, the therapeutic benefits of grapes and other byproducts have been empirically used for medical purposes such as bleeding, pain, inflammation nausea, diarrhea, gastroenteritis, or skin diseases. Moderated intake of the red wine improves parameters as blood lipids, endothelial dysfunction, platelet aggregation, and other risk factors for cardiovascular disease. However, few studies have been explored the potential benefits from vine byproducts. Vine leaves, a waste product from the vine, are also rich source of polyphenols and other therapeutic compounds. In this chapter, we explored the therapeutic properties from vine leaf in different biological systems.

Consumo exacerbado de lipídeos provoca dano celular em algumas doenças metabólicas e cardiovasculares

Objective: To review the deleterious biochemical mechanisms related to changes of oxidative stress and inflammation, provoked by excessive consumption and accumulation of lipids in different tissues, in cardiovascular diseases, diabetes and metabolic syndrome. Data source: This review article was based on papers selected for their relevance from databases such as Science Direct, PubMed and SciELO, published between 1995 and 2014. The search included the following keywords: High-fat diet, obesity, oxidative stress, inflammation. Data synthesis: Evidence suggests that the deleterious effects of lipotoxicity are related to ectopic deposition, activation of lipolysis, formation of lipid metabolites, generation of reactive oxygen species and oxidative stress, as well as to stimulation of inflammatory cascades. In this context, the simultaneous activation of these biochemical mechanisms interferes with intracellular signaling cascades, disrupting homeostasis, leading to systemic cellular damage or even lipoapoptosis. Conclusions: The identification of the biochemical cellular pathways involved in the process provides an understanding of the molecular mechanisms and, especially, may identify potential therapeutic targets