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The increased circulation of norepinephrine, found in the diseased heart as a result of sympathetic nervous system overactivation, is responsible for its cardiotoxic effects including pathological hypertrophy, cell death, and oxidative stress. Bucindolol is a third generation adrenergic blocker, which acts on the β1 and β2 receptors, and has additional α1 antagonist activity. Thus, the aim of this study was to investigate the action of bucindolol on oxidative stress, hypertrophy, cell survival, and cell death signaling pathways in H9c2 cardiac cells exposed to norepinephrine. H9c2 cells were incubated with 10 μM norepinephrine for 24 h in the presence or absence of bucindolol (10 μM) treatment for 8 h. Western blot was used to determine the expression of proteins for hypertrophy/survival and death signaling pathways. Flow cytometry was used to assess cell death via caspase-3/7 activity and propidium iodide and reactive oxygen species via measuring the fluorescence of CM-H2DCFDA. Norepinephrine exposure resulted in an increase in oxidative stress as well as cell death. This was accompanied by an increased protein expression of LC3B-II/I. The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway which is involved in cardiac remodeling process was activated in response to norepinephrine and was mitigated by bucindolol. In conclusion, bucindolol was able to modulate cardiac remodeling which is mediated by oxidative stress.

Objective Hyperthyroidism causes many injuries in its target organs and the consequences are reflected systemically. As systemic alterations in hyperthyroidism at earlier stages have received partial attention, this study aimed to investigate systemic redox and inflammatory status at an early stage of T4-induced hyperthyroidism. Materials and methods Male Wistar rats were assigned to control and hyperthyroid groups (n = 7/group). The hyperthyroid group received L-thyroxine (12 mg/L) in their drinking water for 14 days whereas control group received only the vehicle. Body weight was measured on the 1st and 14th day of the protocol. On the 14th day, animals were anaesthetized. Blood was then collected from the retro-orbital venous plexus and then the animals were euthanised. The blood was separated into plasma and erythrocytes. Plasma was used to measure ROS levels, sulfhydryl compounds, IL-10, TNF-α and LDH levels; erythrocytes were used for the analysis of thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes (total G6PD, G6PD and 6PGD). Results Hyperthyroid animals presented body weight gain and final body weight reduction, which was associated with increased ROS levels and decreased sulfhydryl content in plasma. Thioredoxin reductase activity, glutaredoxin content, and pentose cycle enzymes levels in erythrocytes, as well as IL-10, TNF-α and LDH plasma levels were unaltered. Conclusion Taken together, our results suggest an impairment in corporal mass associated with systemic oxidative stress at this stage of hyperthyroidism. Meanwhile, the pentose cycle was not influenced and systemic inflammation and tissue damage seem to be absent at this stage of hyperthyroidism.

Introduction: Heart failure is a clinical syndrome characterized by sympathetic/ renin-angiotensin system activation, besides parasympathetic activity attenuation. In the initial phase of HF, following a myocardial infarction, there is impairment of the ventricular function and this can be influenced by the myocardium ischemia area in addition to alteration in the autonomic control of the heart. The aim of this study is to evaluate the hemodynamic responses and autonomic nervous system and its associations in infarcted rats by left coronary artery ligation. Methods: Forty male rats were submitted to left coronary artery ligation: infarcted animals with fifteen days from cardiac surgery (I15), infarcted animals with thirty days from cardiac surgery (I30) and sham-operated groups (S15 and S30), with 10 animals in each group. Basal hemodynamic data and heart rate variability (spectral analysis) were evaluated. Results: Compared to control groups, the infarcted rats demonstrated the following complications: a) cardiac hypertrophy (I30); b) pulmonary congestion (I30); c) mean arterial pressure (MAP), systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) reduction; d) left ventricular systolic pressure (LVSP) reduction and left ventricular end-diastolic pressure (LVEDP) rise; e) contractile (+dP/dt) and relaxation derivatives (-dP/dt) reduction; f) sympathetic cardiac activity increase, and parasympathetic cardiac activity reduction (I30). Conclusion: Our study shows that the infarcted animals presented left ventricular dysfunction, which was influenced by the infarct size. In addition, impairment of autonomic control was present only in the animals belonging to the I30 group, probably due to the degree of cardiac decompensation and disease progression. Keywords: Heart failure; myocardial infarction; heart rate variability

Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-α, TNF-α, MyD88, p-NFκB, NFκB, p-p38, and p38. Reduced expression of p53 and PGC1-α was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-α and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy.

Vitamin E (vit. E) and vitamin C (vit. C) are antioxidants that inhibit nociception. The effect of these vitamins on oxidative-stress markers in the spinal cord of rats with chronic constriction injury (CCI) of the sciatic nerve is unknown. This study investigated the effect of intraperitoneal administration of vit. E (15 mg·kg-1·day-1) and vit. C (30 mg·kg-1·day-1), given alone or in combination, on spinal cord oxidative-stress markers in CCI rats. Adult male Wistar rats weighing 200–250 g were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received injections of vitamins or vehicle (saline containing 1% Tween 80) for 3 or 10 days (n=6/each group). The vitamins prevented the reduction in total thiol content and the increase in superoxide-anion generation that were found in vehicle-treated CCI rats. While nitric-oxide metabolites increased in vehicle-treated CCI rats 3 days after surgery, these metabolites did not show significant changes in vitamin-treated CCI rats. In all rats, total antioxidant capacity and hydrogen-peroxide levels did not change significantly. Lipid hydroperoxides increased 25% only in vehicle-treated CCI rats. These changes may contribute to vit. C- and vit. E-induced antinociception, because scavenging reactive oxygen species seems to help normalize the spinal cord oxidative status altered by pain.

We determined the antioxidant potential of fractions obtained from leaves ofSchinus terebinthifolius, a medicinal plant known in Brazil as aroeira, to select the fraction with the best yield and antioxidant performance. These qualities were found in the methanol fraction (MeF), which was administered intraperitoneally (20 mg/kg/day) for 3 and 10 days to rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. The MeF increased the mechanical and thermal thresholds that had been lowered by CCI. In parallel, the lumbosacral spinal cord showed an increase in superoxide dismutase but a decrease in glutathione peroxidase and glutathione-S-transferase activities in saline- and MeF-treated CCI rats. Catalase activity decreased only in saline-treated CCI rats for 10 days. Total thiols decreased in saline- and MeF-treated CCI rats. Ascorbic acid increased in these rats at day 3 but only in saline-treated CCI rats at day 10. No change was found in hydrogen peroxide and lipid hydroperoxide. Open-field and elevated plus-maze tests and blood parameters of liver function did not change. Thus, the MeF from leaves ofS. terebinthifoliushas an antinociceptive action with no toxic effects, and it affects oxidant biomarkers in the spinal cord of rats with CCI.

Introduction: Important changes in human dietary pattern occurred in recent decades. Increased intake of processed foods leads to obesity, which is related with the development of chronic diseases such as type 2 diabetes mellitus, hypertension, as well as cardiovascular and chronic kidney diseases. The prevalence of hypertension has also dramatically increased in recent years, and high sodium intake contributes to this scenario. In healthy individuals, kidneys are the primary end-organs that regulate sodium homeostasis. This study aims to evaluate renal function parameters and systolic blood pressure measurements in an animal model of obesity. Methods: Sixty-day-old male Wistar rats (n=30) were divided into two groups: standard (SD) and cafeteria diet (CD). Cafeteria diet was altered daily and was composed by crackers, wafers, sausages, chips, condensed milk, and soda. All animals had free access to water and chow and the experiment was carried out for 6 weeks. Weight gain, sodium and liquid intake control, systolic blood pressure measurements, and renal function parameters were evaluated. Results: Animals exposed to cafeteria diet had an increase of 18% in weight compared to the control group. Sodium intake was increased by cafeteria diet and time (F (1,28) = 773.666, P=0.001 and F (5,28) = 2.859, P=0.02, respectively) and by the interaction of both factors (F (6,28) = 2.859, P=0.02). On liquid intake occurred only effect of cafeteria diet and time (F (1,28) = 147.04, P=0.001 and F (5,28) =3.996, P=0.003, respectively). Cafeteria diet exposure also induced an increase on creatinine serum levels (P=0.002), however this effect was not observed on creatinine urine levels (P>0.05) nor on systolic pressure measurements (Students’ t test, P>0.05). Conclusions: Obesity induced by cafeteria diet exposure increases liquid intake and alters creatinine serum levels, an important renal function marker. Considering the high consumption of hypercaloric food currently in the world, further studies are required to elucidate the modifications on renal function triggered by this diet over time. Key-words: Hypertension; kidney; renal function; obesity; hypercaloric diet

Introduction : The purpose of this study was to investigate the effects of isolated vitamin B 6 (VB 6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB 6, HcyT, and HB 6 ). On the 30th day of treatment, two groups were supplemented with VB 6 in the drinking water (groups: CB 6 and HB 6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB 6 group. Additionally, GST immunocontent was enhanced (51%) in the HB 6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB 6 group compared to the CB 6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB 6 group. Ejection fraction (EF) was improved in the HB 6 group compared to the HcyT group. E/A ratio was enhanced in the HB 6 group compared to the CB 6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB 6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters. Keywords: Homocysteine; oxidative stress; vitamin B 6.

Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. Objetivo: Determinar os efeitos da administração aguda e crônica de metilprednisolona no estresse oxidativo, por meio da quantificação da peroxidação lipídica (POL) e do potencial antioxidante reativo total (PART), em pulmões de ratos. Métodos: Quarenta ratos Wistar foram divididos em quatro grupos: tratamento agudo, com ratos recebendo uma dose única de metilprednisolona (50 mg/kg i.p.); controle agudo, com ratos recebendo injeção unida de salina; tratamento crônico, com ratos recebendo metilprednisolona v.o. na água do bebedouro (6 mg/kg por dia durante 30 dias; e controle crônico, com ratos recebendo água de bebedouro normal). Resultados: Os níveis de PART foram significativamente maiores no grupo tratamento agudo que no grupo controle agudo, sugerindo uma melhora do sistema de defesa pulmonar. Os níveis de POL foram significativamente maiores no grupo tratamento crônico que no grupo controle crônico, indicando dano oxidativo no tecido pulmonar. Conclusões: Nossos resultados sugerem que o uso agudo de corticoides foi benéfico aos tecidos pulmonares, enquanto seu uso crônico não o foi. O uso crônico de metilprednisolona parece aumentar os níveis pulmonares da POL.

This study tested the hypothesis that simvastatin treatment can improve cardiovascular and autonomic functions and membrane lipoperoxidation, with an increased effect when applied to physically trained ovariectomized rats. Ovariectomized rats were divided into sedentary, sedentary+simvastatin and trained+simvastatin groups (n = 8 each). Exercise training was performed on a treadmill for 8 weeks and simvastatin (5 mg/kg) was administered in the last 2 weeks. Blood pressure (BP) was recorded in conscious animals. Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses to BP changes. Cardiac vagal and sympathetic effects were determined using methylatropine and propranolol. Oxidative stress was evaluated based on heart and liver lipoperoxidation using the chemiluminescence method. The simvastatin-treated groups presented reduced body weight and mean BP (trained+simvastatin = 99 ± 2 and sedentary+simvastatin = 107 ± 2 mmHg) compared to the sedentary group (122 ± 1 mmHg). Furthermore, the trained group showed lower BP and heart rate compared to the other groups. Tachycardic and bradycardic responses were enhanced in both simvastatin-treated groups. The vagal effect was increased in the trained+simvastatin group and the sympathetic effect was decreased in the sedentary+simvastatin group. Hepatic lipoperoxidation was reduced in sedentary+simvastatin (≈21%) and trained+simvastatin groups (≈57%) compared to the sedentary group. Correlation analysis involving all animals demonstrated that cardiac lipoperoxidation was negatively related to the vagal effect (r = -0.7) and positively correlated to the sympathetic effect (r = 0.7). In conclusion, improvement in cardiovascular and autonomic functions associated with a reduction of lipoperoxidation with simvastatin treatment was increased in trained ovariectomized rats. Fil: Bernardes, N.. Universidade Nove de Julho; Brasil Fil: Brito, J. O.. Universidade Nove de Julho; Brasil Fil: Fernandes, T. G.. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciencias Basicas Da Saude; Brasil Fil: Llesuy, Susana Francisca. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular; Argentina Fil: Irigoyen, M. C.. Universidade de Sao Paulo; Brasil Fil: Bêllo Klein, A.. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciencias Basicas Da Saude; Brasil Fil: De Angelis, K.. Universidade Nove de Julho; Brasil

Introduction: Oxidative stress seems to be a role in the atherosclerosis process, but research in human beings is scarce. Objective: To evaluate the role of oxidative stress on human aortas of patients submitted to surgical treatment for advanced aortoiliac occlusive disease. Methods: Twenty-six patients were divided into three groups: control group (n=10) formed by cadaveric organ donors; severe aortoiliac stenosis group (patients with severe aortoiliac stenosis; n=9); and total aortoiliac occlusion group (patients with chronic total aortoiliac occlusion; n=7). We evaluated the reactive oxygen species concentration, nicotinamide adenine dinucleotide phosphate-oxidase, superoxide dismutase and catalase activities as well as nitrite levels in samples of aortas harvested during aortofemoral bypass for treatment of advanced aortoiliac occlusive disease. Results: We observed a higher level of reactive oxygen species in total aortoiliac occlusion group (48.3±9.56 pmol/mg protein) when compared to severe aortoiliac stenosis (33.5±7.4 pmol/mg protein) and control (4.91±0.8 pmol/mg protein) groups (P

INTRODUÇÃO: Exercícios de longa duração podem levar ao desequilíbrio entre os sistemas pró e antioxidante, acarretando dano a lipídeos, proteínas e DNA. Entretanto, alguns estudos avaliando triatlo Ironman observaram proteção aos lipídeos. OBJETIVO: Avaliar parâmetros de estresse oxidativo após uma competição de meio Ironman. MÉTODOS: Participaram 11 sujeitos com idade de 31,1 ± 3,3 anos, massa corporal de 72,4 ± 5,4kg, estatura de 176,2 ± 4,8cm, gordura corporal de 9,8 ± 3,3 %, VO2máx na corrida de 60,7 ± 6,0mL/kg/min. Foram mensurados: dano a lipídeos através da quimiluminescência nos eritrócitos e TBARS no plasma, dano a proteínas através das carbonilas plasmáticas, ácido úrico e compostos fenólicos plasmáticos, assim como a atividade antioxidante enzimática da catalase, superóxido dismutase e glutationa peroxidase nos eritrócitos. RESULTADOS: Houve redução na atividade da enzima superóxido dismutase (23,24 ± 1,49 para 20,77 ± 2,69U SOD/mg proteína, p = 0,045), e aumento no ácido úrico (40,81 ± 10,68 para 60,33 ± 6,71mg/L, p < 0,001) logo após a competição. Não houve diferença estatisticamente significativa na atividade das enzimas antioxidantes catalase e glutationa peroxidase e nos compostos fenólicos totais, assim como não foi observado dano a lipídeos (TBARS e quimiluminescência) e proteínas (carbonilas). CONCLUSÃO: Esse grupo de atletas não sofreu estresse oxidativo, provavelmente devido à liberação de ácido úrico e outros antioxidantes no plasma.Ultra-endurance exercises can cause imbalance between the pro and antioxidant systems, leading to lipid, protein and DNA damage. Nevertheless, some studies evaluating Ironman triathlon found protection to lipids. PURPOSE: To evaluate oxidative stress parameters after a half-Ironman competition. METHODS: Eleven subjects aged 31.1 ± 3.3 yr, body weight 72.4 ± 5.4 kg, height 176.2 ± 4.8 cm, body fat 9.8 ± 3.3 %, VO2máx on run 60.7 ± 6.0 mL/kg/min, participated in this study. The following data were measured: lipid damage by chemoluminescence in erythrocyte and TBARS in plasma, protein damage by plasmatic carbonyls, uric acid and phenolic compounds, as well as the antioxidant enzymatic activity of catalase, superoxide dismutase and glutathione peroxidase in erythrocytes. RESULTS: Reduction in superoxide dismutase (23.24 ± 1.49 to 20.77 ± 2.69 U SOD/mg protein, p = 0.045), and increase in uric acid (40.81 ± 10.68 to 60.33 ± 6.71 mg/L, p < 0.001) were found immediately after the competition. No statistically significant differences were found in catalase and glutathione peroxidase or phenolic compounds. Lipid (TBARS and chemoluminescence) or protein (carbonyl) damage was not observed either. CONCLUSION: These athletes did not suffer oxidative stress, probably due to uric acid and other plasmatic antioxidants release in the plasma.

Importance.Autologous serum (AS) eye drops are recommended for severe dry eye in patients with ocular surface disease. No description of the antioxidant balance of AS eye drops has been reported in the literature.Objective.This study sought to evaluate the total reactive antioxidant potential (TRAP) and concentration of reactive oxygen species (ROS) in samples of 50% AS eye drops and their correlations with the demographic characteristics and lifestyle habits of patients with ocular surface disease and healthy controls.Design.This was a case-control study with a 3-month follow-up period.Participants. 16 patients with severe dry eye disease of different etiologies and 17 healthy controls matched by age, gender, and race were included.Results.TRAP and ROS were detected at all evaluated times. There were no differences in the mean ROS (p=0.429) or TRAP (p=0.475) levels between cases and controls. No statistically significant differences in the concentrations of ROS or TRAPs were found at 0, 15, or 30 days (pfor ROS = 0.087 andpfor TRAP = 0.93). Neither the demographic characteristics nor the lifestyle habits were correlated with the oxidative balance of the 50% AS eye drops.Conclusions and Relevance.Both fresh and frozen 50% AS eye drops present antioxidant capacities and ROS in an apparently stable balance. Moreover, patients with ocular surface disease and normal controls produce equivalent AS eye drops in terms of oxidative properties.

OBJETIVO: Estudar os antioxidantes da lágrima humana, estimulada pelo corte de cebola e a possível influência dos hábitos de vida sobre estas medidas. MÉTODOS: A amostra consistiu de dez adultos jovens, que responderam questionário sobre o hábito de fumar, de ingerir bebidas alcoólicas, frutas, vegetais e cereais, de usar vitaminas e/ou drogas e de praticar exercícios. O potencial reativo antioxidante total (TRAP) foi analisado por meio da quimioluminescência do luminol, a superóxido dismutase (SOD) foi medida pela inibição do piragolol e a absorbância de H2O2 a 240 nm foi utilizada para identificar a catalase. RESULTADOS: A média ± DP dos valores de potencial reativo antioxidante total foi 33,8±11,5 µM e de superóxido dismutase foi 10,8±1,9 U/mL. Não foi identificada atividade da catalase. Detectou-se associação entre a prática regular de exercícios e aumento nos valores de potencial reativo antioxidante total (p=0,021), com diferença de 18,6 µM entre os indivíduos que se exercitavam pelo menos uma vez por semana e os sedentários. Sexo masculino e aumento na concentração de potencial reativo antioxidante total também se associaram estatisticamente (p=0,013), com diferença de 16,3 µM entre os sexos. Houve associação entre hábito tabágico e aumento na superóxido dismutase (p=0,041), com diferença de 3,3 U/mL entre fumantes de mais de cinco cigarros/dia e não fumantes. O uso de vitamina C também demonstrou associação com a superóxido dismutase (p=0,018); a diferença para os que tomavam vitamina C foi de 3,3 U/mL a mais. CONCLUSÃO: Os antioxidantes do lacrimejamento reflexo foram mensuráveis em adultos jovens, e diferentes variáveis parecem ter influenciado nos resultados.PURPOSE: To study the antioxidant status of human tears, stimulated by onion fumes and the possible influence of the life habits thereon were measured. METHODS: Subjects were ten healthy young adults, who answered a questionnaire about smoking, alcohol ingestion, fruit, vegetable, cereal, and vitamin intake and/or intake of other drugs, and physical exercise habits. Chemoluminescensce of luminol was used to analyze the total reactive antioxidant potential (TRAP), inhibition of piragollol was used to measure superoxide dismutase (SOD) and absorbance of H2O2 at 240 nm was used to identify catalase. RESULTS: Mean ± SD value for total reactive antioxidant potential was 33.8±11.5 µM and for superoxide dismutase 10.8±1.9 U/mL. Catalase was not identified. Regular exercise was associated with increased total reactive antioxidant potential values (p=0.021), with a difference of 18.6 µM between individuals who exercise at least once a week and sedentary individuals. Male gender and total reactive antioxidant potential values were statistically associated (p=0.013), with a difference of 16.3 µM between genders. There was an association between smoking and increased superoxide dismutase values (p=0.041), with a difference of 3.3 U/mL between smokers of more than five cigarettes/day and non-smokers. Also, vitamin C intake and superoxide dismutase values were associated (p=0.018); the difference for vitamin C takers was 3.3 U/mL. CONCLUSION: Reflex tearing antioxidants were measurable in healthy young adults, and different variables apparently influenced their values.

OBJETIVO: Este é um estudo experimental que visa a avaliar o efeito da insuficiência cardíaca no estresse oxidativo em diafragma de ratos. MÉTODOS: O modelo de infarto do miocárdio por ligadura da artéria coronária esquerda foi utilizado para desenvolvimento de insuficiência cardíaca. No 42º dia após a ligadura coronária, os animais foram mortos e tiveram o diafragma retirado e homogeneizado. O estresse oxidativo foi avaliado em homogeneizados de diafragma através de medidas de lipoperoxidação e de ensaios de atividade enzimática antioxidante: catalase, glutationa peroxidase (enzimas que reduzem o peróxido de hidrogênio à água) e superóxido dismutase (enzima antioxidante que reduz o superóxido a peróxido de hidrogênio). RESULTADOS: Os resultados encontrados foram os seguintes: o modelo de ligadura de artéria coronária esquerda foi efetivo em gerar insuficiência cardíaca, com área média de infarto de 39% da área do ventrículo esquerdo; a lipoperoxidação estava 217% aumentada no diafragma dos animais infartados em relação aos controles; a atividade antioxidante da catalase estava reduzida em 77% e a da glutationa peroxidase em 20%, em comparação com o grupo controle; o infarto não alterou a atividade enzimática da superóxido dismutase. CONCLUSÃO: Os resultados sugerem a presença de estresse oxidativo no músculo diafragmático em animais submetidos à ligadura da artéria coronária esquerda.OBJECTIVE: To use an experimental model to evaluate the effect of heart failure on oxidative stress in the rat diaphragm. METHODS: The model of myocardial infarction was developed through left coronary artery ligation. On day 42 after coronary artery ligation, the animals were killed, after which the diaphragms were collected and homogenized. Oxidative stress was evaluated in diaphragm homogenates through measurement of lipid peroxidation and assays of the activity of antioxidant enzymes, including catalase and glutathione peroxidase (enzymes that reduce hydrogen peroxide to water), as well as superoxide dismutase (an antioxidant enzyme that reduces superoxide anions to hydrogen peroxide). RESULTS: The coronary artery ligation model was found to be effective in causing heart failure. In the animals submitted to coronary artery ligation, the mean infarcted area of the left ventricle was 39%. Lipid peroxidation was 217% greater in the diaphragms of ligated animals than in those of controls. The activity of catalase and glutathione peroxidase was 77% and 20% lower, respectively, in study rats than in control rats. Infarction did not modify superoxide dismutase activity. CONCLUSION: The results suggest that left coronary artery ligation results in oxidative stress in the diaphragm.

The purpose of the present study was to examine myocardial antioxidant and oxidative stress changes in male and female rats in the presence of physiological sex hormone concentrations and after castration. Twenty-four 9-week-old Wistar rats were divided into four groups of 6 animals each: 1) sham-operated females, 2) castrated females, 3) sham-operated males, and 4) castrated males. When testosterone and estrogen levels were measured by radioimmunoassay, significant differences were observed between the castrated and control groups (both males and females), demonstrating the success of castration. Progesterone and catalase levels did not change in any group. Control male rats had higher levels of glutathione peroxidase (50%) and lower levels of superoxide dismutase (SOD, 14%) than females. Control females presented increased levels of SOD as compared to the other groups. After castration, SOD activity decreased by 29% in the female group and by 14% in the male group as compared to their respective controls. Lipid peroxidation (LPO) was assessed to evaluate oxidative damage to cardiac membranes by two different methods, i.e., TBARS and chemiluminescence. LPO was higher in male controls compared to female controls when evaluated by both methods, TBARS (360%) and chemiluminescence (46%). Castration induced a 200% increase in myocardial damage in females as determined by TBARS and a 20% increase as determined by chemiluminescence. In males, castration did not change LPO levels. These data suggest that estrogen may have an antioxidant role in heart muscle, while testosterone does not.

The purpose of the present study was to investigate the effects of experimental diabetes on the oxidant and antioxidant status of latissimus dorsi (LD) muscles of male Wistar rats (220 +/- 5 g, N = 11). Short-term (5 days) diabetes was induced by a single injection of streptozotocin (STZ, 50 mg/kg, iv; glycemia300 mg/dl). LD muscle of STZ-diabetic rats presented higher levels of thiobarbituric acid reactive substances (TBARS) and chemiluminescence (0.36 +/- 0.02 nmol/mg protein and 14706 +/- 1581 cps/mg protein) than LD muscle of normal rats (0.23 +/- 0.04 nmol/mg protein and 7389 +/- 1355 cps/mg protein). Diabetes induced a 92% increase in catalase and a 27% increase in glutathione S-transferase activities in LD muscle. Glutathione peroxidase activity was reduced (58%) in STZ-diabetic rats and superoxide dismutase activity was similar in LD muscle of both groups. A positive correlation was obtained between catalase activity and the oxidative stress of LD, as evaluated in terms of TBARS (r = 0.78) and by chemiluminescence (r = 0.89). Catalase activity also correlated inversely with glutathione peroxidase activity (r = 0.79). These data suggest that an increased oxidative stress in LD muscle of diabetic rats may be related to skeletal muscle myopathy.

We tested the influence of estrogen on coronary resistance regulation by modulating nitric oxide (NO) and hydrogen peroxide (H2O2) levels in female rats. For this, estrogen levels were manipulated and the hearts were immediately excised and perfused at a constant flow using a Langendorff’s apparatus. Higher estrogen levels were associated with a lower coronary resistance, increased nitric oxide bioavailability, and higher levels of H2O2. When oxide nitric synthase blockade by L-NAME was performed, no significant changes were found in coronary resistance of ovariectomized rats. Additionally, we found an inverse association between NO levels and catalase activity. Taken together, our data suggest that, in the absence of estrogen influence and, therefore, reduced NO bioavailability, coronary resistance regulation seems to be more dependent on the H2O2that is maintained at low levels by increased catalase activity.

The objective of this study was to evaluate the changes induced by isolated soy protein (ISP)-based diet on glycemia and oxidative stress biomarkers in diabetic rats. Fifteen male Wistar rats (35 ± 4 g, aged 21 days) were assigned to three groups: Casein (C group), which received casein-based diet during experimental protocol; Diabetic treated with Casein (D + C group) that received casein-based diet before and after diabetes induction; Diabetic treated with ISP (D + S group) that received casein-based diet before diabetes induction and after received ISP-based diet for the experimental protocol. Diabetes was induced by a single dose of streptozotocin (50 mg/kg body weight i.v.). After three weeks of dietary treatment, total nitrates, lipid peroxidation, antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) were measured in heart homogenates. ISP-based diet promoted an improvement in the glycemic levels of diabetic rats compared with casein-based diet (362 ± 25 vs 461 ± 30 mg/dL). CAT activity demonstrated a significant decrease in D + C and D + S groups. D + S group presented a significant increase in SOD and GST activities. Lipid peroxidation was not different among experimental groups. The overall results suggested the potential benefits of ISP-based diet consumption to improve the life quality of diabetic patients.

This study tested whether a low dose (40% less than the pharmacological dose of 17-β estradiol) would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n = 9/group) were divided in three groups: (1) ovariectomized (Ovx), (2) ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg), and (3) high dose (HE; 0.5 mg) 17-β estradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD) and catalase (CAT) activities, redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP), hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy. Fil: Campos, Cristina. Universidade Federal do Rio Grande do Sul; Brasil Fil: Rabello Casali, Karina. Instituto de Cardiologia do Rio Grande do Sul; Brasil Fil: Baraldi, Dhãniel. Universidade Federal do Rio Grande do Sul; Brasil Fil: Conzatti, Adriana. Universidade Federal do Rio Grande do Sul; Brasil Fil: Rosa Araújo, Alex Sander da. Universidade Federal do Rio Grande do Sul; Brasil Fil: Khaper, Neelam. Lakehead University; Canadá Fil: Llesuy, Susana Francisca. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentina Fil: Rigatto, Katya. Universidade Federal de Ciências da Saúde de Porto Alegre; Brasil Fil: Belló Klein, Adriane. Universidade Federal do Rio Grande do Sul; Brasil

This study analyzed and compared the content of isoflavones in 2 soy products the effectiveness of isoflavones as antioxidants in vitro and demonstrated the antioxidant effect of a soy diet in rats with myocardial infarction (MI). Isoflavone content was analyzed in soybean hypocotyl (SH) and isolated soy protein (ISP). The quality (TAR) and quantity (TRAP) of antioxidants present in the samples was quantified. The amount of daidzin was higher in SH (9 times) and genistein in ISP (5 times). SH presented a 3-fold increase in TAR while both products exhibited same TRAP. The rats were fed an ISP diet for 9 weeks. Animals were distributed among 6 treatment groups: (i) Sham Casein; (ii) Infarct Casein < 25%; (iii) Infarct Casein > 25%; (iv) Sham Soy; (v) Infarct Soy < 25%; and (vi) Infarct Soy > 25%. MI was induced 5 weeks after the commencement of the diets. Lipid peroxidation (LPO) antioxidant enzyme activity and levels of nitrites/nitrates were determined in blood. Rats receiving the ISP diet demonstrated increased activity of antioxidant enzyme activity and nitrite/ nitrate content. In addition the increase in LPO seen in rats subjected to MI was significantly mitigated when the ISP diet was given. These findings suggest a nutritional approach of using a soy-based diet for the prevention of oxidative-stress-related diseases such as heart failure. Fil: Hagen, Martine Kienzle. Universidade Federal do Rio Grande do Sul; Brasil Fil: Ludke, Ana. University of Manitoba; Canadá Fil: Araujo, Alex Sander. Universidade Federal do Rio Grande do Sul; Brasil Fil: Mendes, Roberta Hack. Universidade Federal do Rio Grande do Sul; Brasil Fil: Fernandes, Tânia Gatelli. Universidade Federal do Rio Grande do Sul; Brasil Fil: Mandarino, Jose Marcos Gontijo. Universidade Federal do Rio Grande do Sul; Brasil Fil: Llesuy, Susana Francisca. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vogt de Jong, Erna. Universidade Federal do Rio Grande do Sul; Brasil Fil: Belló Klein, Adriane. Universidade Federal do Rio Grande do Sul; Brasil

The study was designed to test whether the ingestion grape juice (GJ) could modulate monocrotaline (MCT)-induced Cor pulmonale resulting from antioxidant properties. Three-week-old male Wistar rats received GJ (10 mL/kg/day) by gavage for 6 weeks. A single injection of MCT (60 mg/kg body weight intraperitoneally) was administered at the end of the third week. Animals were divided in four groups: control, MCT, GJ, and GJ + MCT. MCT promoted a significant increase in right ventricle (36%) and lung (70%) weight to body weight ratio. There was an increase in the right systolic (38%) as well as in the end diastolic (70%) ventricular pressures. MCT caused a significant decrease in lung endothelial nitric oxide synthase (20%) but increase in lipid peroxidation (13%) and catalase (43%). MCT-induced decrease in the endothelial nitric oxide synthase and increase in the right ventricular end diastolic pressure were prevented by GJ, whereas right systolic ventricular pressure and lung weight to body weight ratio were corrected only partially. MCT-induced increase in heart and right ventricle to body weight ratios was not changed by GJ. GJ blunted MCT-induced increase in lipid peroxidation but had no effect on the changes in catalase and superoxide dismutase activities. GJ appears to offer some protection against MCT-induced Cor pulmonale and right ventricle function changes. Copyright © 2010 by Lippincott Williams & Wilkins. Fil: Ludke, Ana R L. University of Manitoba; Canadá Fil: Mosele, Francisca. Universidade Federal do Rio Grande do Sul; Brasil Fil: Caron-Lienert, Rafaela. Universidade Federal do Rio Grande do Sul; Brasil Fil: Ribeiro, Maria Flávia. Universidade Federal do Rio Grande do Sul; Brasil Fil: Partata, W?nia. Universidade Federal do Rio Grande do Sul; Brasil Fil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Analítica y Fisicoquímica; Argentina Fil: Araujo, Alex Sander. Universidade Federal do Rio Grande do Sul; Brasil Fil: Singal, Pawan. University of Manitoba; Canadá Fil: Belló-Klein, Adriane. Universidade Federal do Rio Grande do Sul; Brasil

We investigated the effects of an isolated soy protein (ISP) diet offered over a 9-week period to rats in whom myocardial infarction (MI) had been induced, and a casein diet given as a control. Male Wistar rats were assigned to six groups after infarct size determination (n Z 8/group): Sham Casein (SC); Infarct Casein < 25% (IC < 25%); Infarct Casein > 25% (IC > 25%); Sham Soy (SS); Infarct Soy < 25% (IS < 25%); and Infarct Soy > 25% (IS > 25%). MI surgery was performed at the fifth week, and one month later, the animals were hemodynamically assessed to evaluate left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), contractility and relaxation indexes (dP/dt). Lung and liver specimens were also collected for the estimation of organ congestion. Oxidative stress was evaluated in heart homogenates through chemiluminescence (CL), carbonyl groups, and antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Infarcted groups treated with casein showed cardiac hypertrophy, lung and liver congestion, increased LVEDP and decreased LVSP and dP/dt, all typical signals of heart failure. Ventricular dysfunction was correlated with increased myocardial oxidative damage as seen by CL and carbonyl groups data in the groups IC < 25% and IC > 25% (3 and 10-fold increase, respectively). The ISP diet was able to improve ventricular systolic and diastolic function in the groups IS < 25% and IS > 25% (LVEDP was reduced by 44% and 24%, respectively) and to decrease myocardial oxidative stress. The overall results confirm the preventive role of soy-derived products in terms of post-MI myocardial dysfunction probably by an antioxidant action. Fil: Hagen, Martine Kienzle. Universidade Federal do Rio Grande do Sul; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Lehenbauer Lüdke, Ana Raquel. Universidade Federal do Rio Grande do Sul; Brasil Fil: Paludo, Ana Carolina. Universidade Federal do Rio Grande do Sul; Brasil Fil: Schenkel, Paulo. Universidade Federal do Rio Grande do Sul; Brasil Fil: Gonçalves, Lessane. Universidade Federal do Rio Grande do Sul; Brasil. Pontificia Universidade Católica do Rio Grande do Sul; Brasil Fil: Fernandes, Tânia Gatelli. Universidade Federal do Rio Grande do Sul; Brasil Fil: Caron, Rafaela. Universidade Federal do Rio Grande do Sul; Brasil Fil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidade Federal do Rio Grande do Sul; Brasil Fil: Mill, José Geraldo. Universidade Federal do Espírito Santo; Brasil Fil: Belló Klein, Adriane. Universidade Federal do Rio Grande do Sul; Brasil

Reactive oxygen species are formed in physiological and pathological conditions in mammalian tissues. Because of their high reactivity, they may interact with biomolecules, inducing oxidative injury. Increases in lipid peroxidation can result in oxidative damage to cellular membranes. Protection against oxidative damage is provided by enzymatic and non-enzymatic antioxidant defenses. Antioxidant enzyme activities and lipid peroxidation, as an index of oxidative stress injury, were evaluated in different seasons over one year in the heart and liver of rats, maintained on a 12 h light and dark cycle. Glutathione peroxidase and catalase activities, in both tissues, were maximal in the summer season. Lipid peroxidation in the heart was maximal in the spring as compared to the other seasons and it did not vary in the liver during the year. These findings suggest that any study of antioxidants or oxidative stress must take into account such seasonal variations for a more precise analysis of changes due to any pathological condition. © 2000 Elsevier Science Inc. All rights reserved. Fil: Belló Klein, A.. Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saude; Brasil Fil: Morgan Martins, M. I.. Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saude; Brasil Fil: Barp, J.. Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saude; Brasil Fil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Bioquímica y Medicina Molecular; Argentina Fil: Bello, A. A.. Universidade Federal do Rio Grande do Sul. Instituto de Ciências Básicas da Saude; Brasil Fil: Singal, P. K.. St Boniface General Hospital Research Centre; Canadá

Phenylketonuria (PKU) is an autossomal recessive disease caused by phenylalanine-4-hydroxylase deficiency, which is a liver-specific enzyme that catalyzes the hydroxylation of l-phenylalanine (Phe) to l-tyrosine (Tyr). The deficiency of this enzyme leads to the accumulation of Phe in the tissues and plasma of patients. The clinical characterization of this disease is mental retardation and other neurological features. The mechanisms of brain damage are poorly understood. Oxidative stress is observed in some inborn errors of intermediary metabolism owing to the accumulation of toxic metabolites leading to excessive free radical production and may be a result of restricted diets on the antioxidant status. In the present study we evaluated various oxidative stress parameters, namely thiobarbituric acid-reactive species (TBA-RS) and total antioxidant reactivity (TAR) in the plasma of PKU patients. The activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were also measured in erythrocytes from these patients. It was observed that phenylketonuric patients present a significant increase of plasma TBA-RS measurement, indicating a stimulation of lipoperoxidation, as well as a decrease of plasma TAR, reflecting a deficient capacity to rapidly handle an increase of reactive species. The results also showed a decrease of erythrocyte GSH-Px activity. Therefore, it is presumed that oxidative stress is involved in the pathophysiology of the tissue damage found in PKU.