Abstract Background-Pulmonary arterial hypertension (PAH) increases afterload in the right ventricle (RV), inducing adverse ventricular remodelling. Objective- This study explored the protective effects of thyroid hormones and grape juice on serum biomarkers and proteins related to intermediary metabolism in the RV in a model of PAH. Methods- PAH was induced in Wistar rats via the administration of monocrotaline (60 mg/kg i.p.) and they were subsequently treated with organic grape juice (GJ) and thyroid hormones (TH), administered separately or in combination. Results: The RV systolic diameter significantly increased (20%) in the PAH group compared to the control group (P = 0.002). Total CK, LDH, and ALT levels were reduced (~50%) (P<0.001) in the PAH+TH+GJ group as compared to PAH group. Glucose, albumin, triglyceride, and total cholesterol levels were reduced (~50%) (P<0.001) in the PAH group; however, these parameters returned to baseline in the PAH+GJ group. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein expression increased two-fold (P<0.001) and PDH protein levels were reduced (~25%) in the PAH+TH+GJ group compared to the PAH group (P<0.001). Conclusion: The data suggest that serum biomarkers can help in the evaluation of this disease, and that this therapeutic approach can attenuate maladaptive remodelling in the PAH model. BackgroundPulmonary Background Pulmonary (PAH RV, , (RV) Objective Methods 60 (6 mgkg mg kg i.p. ip i p GJ (GJ TH, TH (TH) combination Results 20% 20 (20% P 0.002. 0002 0.002 . 0 002 0.002) CK LDH ~50% 50 (~50% P<0.001 P0001 001 (P<0.001 PAHTHGJ Glucose albumin triglyceride however PAHGJ proliferatoractivated proliferator activated 1alpha alpha 1 PGC1α PGCα PGC 1α α (PGC-1α twofold two fold ~25% 25 (~25% P<0.001. Conclusion disease (RV 6 ( i.p (TH 2 (20 000 0.00 00 ~50 5 (~50 P<0.00 P000 (P<0.00 ~25 (~25 (2 0.0 ~5 (~5 P<0.0 P00 (P<0.0 ~2 (~2 0. ~ (~ P<0. P0 (P<0. P<0 (P<0 P< (P<

Resumo Fundamento A remodelação adversa dos vasos pulmonares eleva a pressão pulmonar e provoca hipertensão arterial pulmonar (HAP). A HAP resulta em aumento da pós-carga do ventrículo direito (VD), causando hipertrofia ventricular e consequente insuficiência cardíaca. Não existe um tratamento específico para o remodelamento desadaptativo do VD secundário à HAP. Objetivos Este estudo tem como objetivo explorar duas abordagens terapêuticas, o suco de uva (SU) e os hormônios tireoidianos (HT), no tratamento do estresse oxidativo induzido pela HAP e nas alterações funcionais cardíacas. Métodos Parâmetros ecocardiográficos relacionados à resistência dos vasos pulmonares (relação TA/TE), contratilidade do VD (ESPAT) e função diastólica do VD (relação dos picos E/A) foram avaliados. Além disso, foram medidos ROS totais, peroxidação lipídica, enzimas antioxidantes, proteínas de manipulação de cálcio, expressão de proteínas pró-oxidantes e antioxidantes. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados Ambos os tratamentos, com SU e HT, demonstraram uma redução na resistência pulmonar (~22%), além de melhorias na ESPAT (inotropismo ~11%) e na relação TA/TE (~26%) (p<0,05). Não houve alterações entre os grupos na relação do pico de E/A. Embora ROS e TBARS não tenham sido estatisticamente significativos, os tratamentos com SU e HT diminuíram os níveis de xantina oxidase (~49%) e normalizaram a expressão de HSP70 e proteínas de manipulação de cálcio (p<0,05). No entanto, apenas o tratamento com HT melhorou a função diastólica (~50%) e aumentou o imunoconteúdo de NRF2 (~48%) (p<0,05). Conclusões Até onde sabemos, este estudo é pioneiro ao mostrar que o HT administrado em conjunto com o SU promoveu melhorias funcionais e bioquímicas em um modelo de HAP. Além disso, nossos dados sugerem que os tratamentos com SU e HT se mostraram cardioprotetores, sejam combinados ou não, e exibiram seus benefícios ao modular o estresse oxidativo e as proteínas de manipulação do cálcio. . (HAP) póscarga pós carga VD, , (VD) cardíaca terapêuticas (SU (HT) cardíacas TA/TE, TATE TA TE TA/TE) (ESPAT E/A EA E avaliados disso totais lipídica antioxidantes próoxidantes pró oxidantes p005 p 0 05 p<0,0 significativos ~22%, 22 ~22% (~22%) inotropismo ~11% 11 ~26% 26 (~26% p<0,05. (p<0,05) ~49% 49 (~49% HSP HSP7 entanto ~50% 50 (~50% NRF ~48% 48 (~48% sabemos cardioprotetores (HAP (VD (HT p00 p<0, 2 ~22 (~22% ~11 1 ~26 (~26 (p<0,05 ~49 4 (~49 ~50 5 (~50 ~48 (~48 p0 p<0 ~2 (~22 ~1 (~2 (p<0,0 ~4 (~4 ~5 (~5 p< ~ (~ (p<0, ( (p<0 (p< (p

Abstract Background Adverse remodeling of lung vessels elevates pulmonary pressure and provokes pulmonary arterial hypertension (PAH). PAH results in increased right ventricle (RV) afterload, causing ventricular hypertrophy and the onset of heart failure. There is no specific treatment for maladaptive RV remodeling secondary to PAH. Objectives This study aims to explore two therapeutic approaches, grape juice (GJ) and thyroid hormones (TH), on PAH-induced oxidative stress and cardiac functional changes. Methods Parameters of echocardiography related to lung vessel resistance (AT/ET ratio), RV contractility (TAPSE), and RV diastolic function (E/A peaks ratio) were evaluated. Also, total ROS, lipid peroxidation, antioxidant enzymes, calcium handling proteins, pro-oxidant and antioxidant protein expression were measured. Values of p<0.05 were considered statistically significant. Results Both GJ and TH treatments demonstrated reductions in pulmonary resistance (~22%) and improvements in TAPSE (inotropism ~11%) and AT/ET ratio (~26%) (p<0.05). There were no changes amongst groups regarding the E/A peak ratio. Although ROS and TBARS were not statistically significant, GJ and TH treatments decreased xanthine oxidase (~49%) levels and normalized HSP70 and calcium handling protein expression (p<0.05). However, only TH treatment ameliorated diastolic function (~50%) and augmented NRF2 immunocontent (~48%) (p<0.05). Conclusions To the best of our knowledge, this study stands as a pioneer in showing that TH administered together with GJ promoted functional and biochemical improvements in a PAH model. Moreover, our data suggest that GJ and TH treatments were cardioprotective, combined or not, and exhibited their beneficial effects by modulating oxidative stress and calcium-handling proteins. . (PAH) (RV afterload failure approaches (GJ TH, , (TH) PAHinduced induced ATET AT ET ratio, TAPSE, (TAPSE) EA E A evaluated Also peroxidation enzymes proteins prooxidant pro oxidant measured p005 p 0 05 p<0.0 significant ~22% 22 (~22% inotropism ~11% 11 ~26% 26 (~26% p<0.05. (p<0.05) ~49% 49 (~49% HSP HSP7 However ~50% 50 (~50% NRF ~48% 48 (~48% knowledge model Moreover cardioprotective calciumhandling (PAH (TH (TAPSE p00 p<0. ~22 2 (~22 ~11 1 ~26 (~26 (p<0.05 ~49 4 (~49 ~50 5 (~50 ~48 (~48 p0 p<0 ~2 (~2 ~1 (p<0.0 ~4 (~4 ~5 (~5 p< ~ (~ (p<0. ( (p<0 (p< (p

Abstract This study explored the association of cardioprotective role of thyroid hormones (TH) and benefit effects of grape juice (GJ) on vascular function against the apoptosis and inflammation associated with monocrotaline (MCT)-induced pulmonary hypertension (PH). Wistar rats were distributed into five groups: control; PH (MCT 60mg/kg i.p.); PH+GJ (GJ-7 µL/g / day, gavage for 14 days); PH+TH (T3, 2μg/100g/day, and T4, 8μg/100g/day, by gavage for 14 days); and PH+TH+GJ. Echocardiographic, morphometric measurements and expression of proteins associated with apoptosis and inflammation were evaluated. The reduced cardiac output (35%) in PH was attenuated in the PH+GJ, PH+TH, and PH+TH+GJ groups (P<0.05). Both GJ and TH had no effect on the PH-induced hypertrophy index. The PH + TH group showed reduced BAX (~90%) and increased Bcl2 levels (~80%) as compared to PH group (P<0.05). The PH-induced increase in caspase 3 was diminished (~92%) in the PH+TH (P<0.05). Both GJ and TH, isolated and combined, reduced caspase 9 levels (~70%). PH-provoked elevated NLRP3 levels was decreased (~90%) in PH+TH (P<0.05). The therapeutic approach showed cardioprotective effects in the PH model which may be mediated by mitigation of apoptosis and inflammation. (TH (GJ MCTinduced MCT induced PH. . (PH) control 60mgkg mgkg 60mg kg mg i.p. ip i p i.p.) PHGJ GJ7 7 (GJ- µLg µL g day 1 days days) PHTH T3, T3 T (T3 2μg100gday μggday 2μg 100g μg 2μg/100g/day T4 8μg100gday 8μg 8μg/100g/day PHTHGJ Echocardiographic evaluated 35% 35 (35% P<0.05. P005 P P<0.05 0 05 (P<0.05) PHinduced index ~90% 90 (~90% Bcl ~80% 80 (~80% ~92% 92 (~92% combined ~70%. 70 ~70% (~70%) PHprovoked provoked NLRP (PH i.p (T gday (35 P00 P<0.0 (P<0.05 ~90 (~90 ~80 8 (~80 ~92 (~92 ~70 (~70% (3 P0 P<0. (P<0.0 ~9 (~9 ~8 (~8 ~7 (~70 ( P<0 (P<0. ~ (~ (~7 P< (P<0 (P< (P

Abstract The enzyme acetylcholinesterase participates in the end of cholinergic transmission and it has been shown that its activity is increased in some diseases that affect the brain, including Alzheimer disease. The objective of this study was to investigate the effect of purple grape juice consumption with or without high-fat diet in the gestational and lactation period on acetylcholinesterase activity and oxidative stress parameters in the hippocampus of female descendants. During pregnancy and lactation, 40 female Wistar rats received a control diet or a high-fat diet, with half of them receiving grape juice. After lactation, the female descendants received water and control diet in ad libitum until euthanasia on the 120 postnatal day. Hippocampus from were removed for analysis of AChE activity, protein oxidation and lipid peroxidation. It was observed that high-fat diet consumption during the pregnancy increased the AChE activity and the grape juice reduced this activity in descendants. The same was observed in protein oxidation, the descendants from high-fat diet had significantly highest values, and grape juice decreased the levels. We conclude that dietary choices during pregnancy can alter the acetylcholinesterase levels and grape juice is an important alternative to improve this function in adulthood.

Abstract Physiological levels of reactive oxygen species (ROS) are important for intracellular and extracellular redox regulation in signaling and defense processes. Strenuous exercise can also contribute to this imbalance, and the muscle fatigue, evidenced by impaired strength or power generation, can be caused by various reasons, including oxidative stress. Antioxidants can prevent the formation of ROS by intercepting free radicals. Twenty judo athletes were included in this randomized, double-blind clinical trial into grape juice and placebo groups, and they consumed grape juice or placebo daily for 14 days in a crossover model. The outcomes were analyzed before and after combat simulations. The upper limb strength was higher in the grape juice group than in the placebo (p [group] = 0.003). The lipid damage levels were 10% higher in the placebo group (p [interaction] = 0.048). During the pre-exercise, the placebo group showed 19% more DNA damage than the grape juice group. The superoxide dismutase activity was 80% lower in the grape juice group (p [interaction] < 0.001). The consumption of grape juice can improve parameters of oxidative stress by reducing the lipid and DNA damage.

ABSTRACT Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

ABSTRACT Vitis labrusca L. is the main species used for wine and juice production in Brazil. The grapevine leaves can be used both as functional foods and as cheapest sources for the extraction of phenolic compounds. Besides the antioxidant activity, grapevine leaves exhibited significant anti-inflammatory activity. Therefore, the aim of this study was to develop and validate an analytical methodology to determine the metals selenium (96Se), chromium (53Cr), nickel (62Ni), cadmium (111Cd) and lead (206Pb) in 30 samples of grapevine leaf extracts (Vitis labrusca, Bordo cultivar) using inductively coupled plasma mass spectrometry (ICP-MS). To obtain the grapevine leaf extracts the samples were milled, weighed and digested in microwave oven with nitric acid. The method showed linearity, precision, accuracy and limits of quantification and detection acceptable for INMETRO protocol validation of analytical methods. Therefore, the method using ICP-MS was developed and validated to determine metals concentrations in grapevine leaves of Vitis labrusca L. and the proposed method could be applied in routine analytical laboratory.

Resumo Contexto A obesidade pode estar relacionada a doenças como diabetes, hipertensão arterial e dislipidemia. A cirurgia bariátrica é um dos tratamentos mais eficazes, levando à diminuição de peso e comorbidades. Objetivo Avaliar o perfil metabólico e farmacoterapêutico de pacientes obesos após cirurgia bariátrica. Métodos Trata-se de um estudo observacional transversal retrospectivo, realizado em um hospital localizado na cidade de Porto Alegre, RS, Brasil. Foram avaliados 70 prontuários de pacientes que realizaram cirurgia bariátrica, nos períodos de antes de 2 meses e mais de 6 meses após a cirurgia bariátrica. A análise estatística foi realizada no programa SPSS 17.0®. Resultados A pressão arterial inicial foi de 130/85 mmHg, passando para 120/80 mmHg (p < 0,01). Com relação ao perfil metabólico antes de dois meses, o HDL foi de 34 mg/dL, o colesterol total foi de 195,07 ± 40,17 mg/dL, o LDL foi de 118,22 ± 41,28 mg/dL, os triglicerídeos foram de 141,09 ± 43,39 mg/dL, e a glicemia de jejum foi de 90 mg/dL. Após 6 meses de cirurgia, os valores passaram para 43 mg/dL, 133,67 ± 28,14 mg/dL, 65,53 ± 24,3 mg/dL, 104,41 ± 29,6 mg/dL, e 77 mg/dL, respectivamente (p < 0,01). Com relação ao uso de medicamentos, 41% utilizaram anti-hipertensivos, 39% utilizaram hipolipemiantes, 10% utilizaram hipoglicemiantes orais e 97% utilizaram suplementos antes dos 2 meses de cirurgia. Após os 6 meses, os percentuais foram alterados para 21%, 19%, 9% e 99%, respectivamente. Conclusões O estudo mostra o sucesso da cirurgia bariátrica em pacientes obesos com comorbidades, revelando melhora no perfil metabólico e redução na utilização de medicamentos para tratamento de comorbidades.

Abstract Background Obesity can be associated with diseases such as diabetes, arterial hypertension and dyslipidemia. Bariatric surgery is one of the most effective treatments available, reducing both weight and comorbidities. Objective To evaluate the metabolic and pharmacotherapeutic profile of obese patients after bariatric surgery. Methods This is a retrospective, cross-sectional, observational study conducted at a hospital located in the city of Porto Alegre, RS, Brazil, based on analysis of the medical records for 70 patients who underwent bariatric surgery covering periods spanning from 2 months prior to more than 6 months after their bariatric surgery. Statistical analysis was conducted using SPSS 17.0®. Results Initial arterial blood pressure was 130/85 mmHg, 6 months after surgery it was 120/80 mmHg (p < 0.01). The metabolic profile 2 months before surgery was as follows: HDL was 34 mg/dL, total cholesterol was 195.07 ± 40.17 mg/dL, LDL was 118.22 ± 41.28 mg/dL, triglycerides were 141.09 ± 43.39 mg/dL, and fasting glycemia was 90 mg/dL. The same figures 6 months after surgery were 43 mg/dL, 133.67 ± 28.14 mg/dL, 65.53 ± 24.3 mg/dL, 104.41 ± 29.6 mg/dL, and 77 mg/dL, respectively (p < 0.01). Use of medications 2 months before surgery was as follows: 41% were on antihypertensives, 39% on hypolipidemics, 10% on oral hypoglycemics, and 97% were on nutritional supplements. These percentages 6 months after surgery had changed to 21%, 19%, 9% and 99%, respectively. Conclusions This study illustrates that bariatric surgery for obese patients with comorbidities was successful, demonstrating improvements in their metabolic profile and reductions in use of medications used to treat comorbidities.

O objetivo deste estudo foi avaliar a hepatoproteção do extrato de folhas de videira (Vitis labrusca) orgânica e convencional. Foram avaliados o conteúdo de polifenóis totais e os polifenóis isolados por HPLC. Os animais receberam injeções intraperitoneais de salina ou extratos (de folha orgânica ou convencional - 30 mg/kg), durante 14 dias. No 15º dia, os ratos receberam tetracloreto de carbono (CCl4) ou óleo mineral (i.p.). Após 4 horas, os animais foram eutanasiados. A análise da atividade das enzimas hepáticas (AST, ALT, GGT) foi feita usando soro, obtido através do sangue e os níveis de peroxidação lipídica (TBARS), oxidação proteica (Carbonil), e da atividade das enzimas antioxidantes superóxido dismutase e catalase foram analisados no fígado. Os resultados demonstraram que o extrato orgânico é mais rico em polifenol e resveratrol do que o convencional. Ambos os extratos previnem a peroxidação lipídica e oxidação proteica gerada pelo CCl4. Além disto, os extratos demonstraram capacidade em modular a atividade de SOD e CAT, bem como em estabelecer um equilíbrio na relação de SOD/CAT. Nós também encontramos que o CCl4 aumentou os níveis de AST e GGT, e que ambos os extratos previnem isto. Estes resultados indicam que os extratos de folhas de videira, ambos, orgânico e convencional, podem prevenir desordens do fígado.

The aim of this study was to evaluate the hepatoprotection of organic and conventional grapevine leaves extract (Vitis labrusca). The total polyphenol content and the isolate polyphenols by HPLC were evaluate. The animals received intraperitoneal injections of saline or extracts (conventional or organic - 30 mg/kg) for 14 days. On day 15, the rats received carbon tetrachloride (CCl4) or mineral oil (i.p.). After 4h, the animals were euthanized. The analysis of the liver enzymes activity (AST, ALT, GGT) was performed using serum, obtained by blood and the levels of lipid peroxidation (TBARS), protein oxidation (carbonyl), and the activity of antioxidant enzymes superoxide dismutase and catalase were analyzed in the liver. The results showed that the organic extract is richer in polyphenol and resveratrol than the conventional one. Both extracts prevent lipid peroxidation and protein oxidation generated by CCl4. Moreover, the extracts demonstrated ability to modulate the activity of SOD and CAT, as well as to establish a balance in the ratio of SOD/CAT. We also found that the CCl4 increased the levels of AST and GGT, and that both extracts prevent this. These results indicate that grapevine leaves extracts, both, organic and conventional, can prevent liver disorders.

O estresse oxidativo tem sido referido como um dos fatores responsáveis pelo desencadeamento de hepatopatias, sendo necessárias novas formas de tratamento. O presente estudo teve como objetivo avaliar a capacidade antioxidante in vitro do chá de Echinodorus grandiforus “Chapéu de couro” em fígado de ratos. Nas diferentes preparações de chá foram avaliadas a composição fenólica, a atividade antioxidante pelo ensaio do DPPH e a capacidade de inibição de peroxidação lipídica induzida por sulfato de cobre. A atividade antioxidante foi avaliada em tecidos hepáticos tratados com azida sódica na presença ou ausência de chá, por meio do ensaio de peroxidação lipídica (TBARS), oxidação proteica (Carbonil) e atividade das enzimas antioxidantes catalase (CAT) e superóxido dismutase (SOD). Os resultados demonstram que as diferentes concentrações de chá são fontes importantes de polifenóis, destacando o conteúdo de teobromina, catequina e vitexina. Além disto, os resultados indicam que o chá apresenta atividade antioxidante pela sua capacidade em varrer o radical DPPH. As diferentes preparações de chá foram capazes de impedir os danos a lipídios e proteínas induzidos pela azida sódica, bem como auxiliar no restabelecimento da atividade de enzimas CAT e SOD. Deste modo, pode-se verificar que o chá E. grandiflorus apresentou atividade antioxidante no soro e no fígado, sendo capaz de prevenir danos oxidativos gerados pela azida sódica.

Oxidative stress has been considered as one of the factors responsible for hepatic diseases, which sometimes require new ways of treatment. The present study aimed to evaluate the in vitro antioxidant capacity of the tea of Echinodorus grandiforus (“leather hat” plant) in rat liver. Different preparations of tea were evaluated for phenolic composition, antioxidant activity by DPPH assay and ability to inhibit lipid peroxidation induced by copper sulfate. The antioxidant activity was assessed in liver tissue treated with sodium azide in the presence or absence of tea by assays for lipid peroxidation (TBARS), protein oxidation (carbonyl) and the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). The results show that different preparations of tea are important sources of polyphenols and contain theobromine, catechin and vitexin. Furthermore, the results indicate that this tea exhibits an antioxidant activity by its ability to scavenge DPPH radical. Different preparations of tea prevented damage to lipids and proteins induced by sodium azide, as well as assisting in restoring CAT and SOD activities. Thus, it can be seen that E. grandiforus tea had antioxidant activity in serum and liver being able to prevent oxidative damages generated by sodium azide.

O objetivo deste estudo foi avaliar os efeitos benéficos de extratos de folhas de videira (Vitis labrusca L.) orgânicas e convencionais em reduzir o dano gerado pelo peróxido de hidrogênio no fígado, coração e rim de ratos Wistar, pela medida de danos a lipídios e a proteínas (Ensaio Carbonyl), como também a modulação sob a atividade das enzimas antioxi-dantes superoxido dismutase e catalase. A pré-incubação com 5 mg/mL de extratos de folhas de videira (Vitis labrusca L.) orgânicas e convencionais previnem ambos danos oxidativos a lipídios e proteínas em todos os tecidos analisados. O extrato de folha orgânica foi capaz de restabelecer a atividade das enzimas superóxido dismutase (rim e fígado) e catalase (coração), as quais foram modificadas pelo tratamento com peróxido de hidrogênio. O extrato convencional foi capaz de restabelecer apenas a enzima catalase no fígado e no coração. Os efeitos do extrato da folha V. labrusca mostrados neste estudo, provavelmente, poderiam ser importantes para a formulação de suplementos dietéticos, bem como para o desenvolvimento de novos ingredientes com propriedades antioxidantes provenientes de outras plantas.

The purpose of this study was to evaluate the beneficial effects of organic and conventional grapevine (Vitis labrusca L.) leaf extracts in reducing hydrogen peroxide-induced stress in the liver, heart and kidney of Wistar rats by measuring lipids and proteins damages (carbonyl assay), as well as the activity of the antioxidant enzymes superoxide dismutase and catalase. The preincubation with 5 mg/mL of organic and conventional grapevine (Vitis labrusca L.) leaf extracts prevented both lipids and proteins oxidative damages in all tissues analyzed. The organic leaf extract was able to restore superoxide dismutase (kidney and liver) and catalase (heart) activities, which were modified by the treatment with H2O2. The conventional extract was able to restore only the catalase activity in liver and heart tissues. The beneficial effects of the V labrusca leaf extract shown in this study could probably be important for formulating dietary supplements, as well as for developing new ingredients with improved antioxidant properties from other plant sources.