Efeitos da vareniclina no tecido pulmonar em modelo animal / Effects of varenicline on lung tissue in the animal model

RESUMO Objetivo O objetivo deste estudo foi investigar os efeitos agudos e crônicos da vareniclina no tecido pulmonar em um estudo experimental. Métodos Um total de 34 ratos foi alocado aleatoriamente em grupos de estudo (vareniclina) e controle. Assim, os ratos foram divididos em dois grupos: (i) grupo controle e (ii) grupo vareniclina. A seguir, os ratos de cada grupo foram, por sua vez, subdivididos igualmente em agudos (C1; V1) e crônicos (C2; V2), e todos os ratos dos grupos agudos e crônicos foram sacrificados sob anestesia: no 45.º dia, para o grupo agudo [C1 (n=5) e V1 (n=12)], e no 90.º dia, para o grupo crônico [C2 (n=5) e V2 (n=12)], respectivamente. Em seguida, foram realizadas análises bioquímicas e histopatológicas. Resultados Trinta e quatro ratos completaram o estudo. Destes ratos, 24 estavam no grupo vareniclina e 10 no grupo controle. Na exposição crônica à vareniclina, os níveis de oxidante composto por malondialdeído (MDA) e mieloperoxidase (MPO) aumentaram, e os níveis de superóxido dismutase (SOD), catalase (CAT), glutationa (GSH) e glutationa peroxidase (GPx), nomeados como antioxidantes, diminuiram significativamente quando comparados com o grupo controle. Os níveis de MDA e MPO também foram significativamente mais elevados e os níveis de SOD, CAT, GPx e GSH foram significativamente mais baixos no grupo vareniclina crônico, quando comparado ao grupo vareniclina agudo. Estes achados também foram confirmados por observações histopatológicas. Conclusões Este é o primeiro estudo que avaliou os efeitos pulmonares da vareniclina experimentalmente em um modelo animal. Observamos que o tratamento crônico da vareniclina causa inflamação e lesão pulmonar.

ABSTRACT Objective This study aimed to investigate acute and chronic effects of varenicline on lung tissue in an experimental study. Methods A total of 34 rats were randomly allocated into study (varenicline) and control groups. The rats were divided into two groups (i) control group, (ii) varenicline group. Then, the rats in the each group were sub-divided equally in turn as acute (C1; V1) and chronic (C2; V2) ; all rats of acute and chronic groups were sacrificed under the anesthesia on the 45th day for acute group [C1 (n=5) and V1 (n=12)] and the 90th day for chronic group [C2 (n=5) and V2 (n=12)], respectively. Thus, biochemical and histopathological analysis were carried out. Results Thirty four rats completed the study, 24 were in varenicline group and 10 were in control group. In chronic exposure to varenicline, oxidant levels comprising of malondialdehyde (MDA), and myeloperoxidase (MPO) increased and superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) levels, named as antioxidants, decreased significantly when compared to the control group. MDA and MPO levels were also significantly higher and SOD, CAT, GPx, GSH levels were also significantly lower in chronic varenicline group when compared to acute varenicline group. These findings were also supported by histopathological observations. Conclusion This is the first study, which evaluated pulmonary effects of varenicline experimentally on an animal model. It was observed that chronic varenicline treatments cause inflammation and lung cell injury.

Altered Tregs and oxidative stress in pregnancy associated lupus

Abstract Aim SLE is a systemic autoimmune disease generally affecting woman in the reproductive age. It is associated with an altered level of Tregs and oxidative stress while an increase in Tregs, and different antioxidant mechanisms to combat oxidative stress are essential for successful pregnancy. Hence, this study aims to determine the level of CD4+ and CD8+ Tregs and oxidative stress in pregnant lupus patients. Methods Ten healthy and 10 pregnant lupus volunteers from the North Indian population, within the age group of 20-30 years were enrolled in the study. All the patients were non-smokers, non-alcoholics and were not associated or undergoing therapy for any other disease. They had a SLEDAI of 37.4 ± 7.32 with 5.2 ± 1.93 years of disease duration. Oxidative stress was determined by measuring the enzyme activity of anti-oxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) and the level of reduced glutathione and lipids peroxidised, spectrophotometrically. Flowcytometry was performed for immunophenotyping to determine CD8+ and CD4+ Tregs. Results Elevated CD8+ Tregs and diminished CD4+ Tregs were observed in pregnant lupus patients. Oxidative stress was significantly increased as the activities of anti-oxidant enzymes and level of reduced glutathione was considerably diminished. There was a substantial increase in the amount of lipids peroxidised. Conclusion Pregnant lupus patients undergo considerable level of oxidative stress in comparison to healthy pregnant woman. The decreased level of CD4+ Tregs and an increase in CD8+ Tregs might be another important factor responsible for pregnancy associated complications. Hence, lupus leads to alterations in the necessary conditions for a successful pregnancy, which might eventually cause higher mortality, morbidity and associated complications.

Evaluation of redox profiles in exogenous subclinical hyperthyroidism at two different levels of TSH suppression

ABSTRACT Objective: Evaluate the relationship between exogenous subclinical hyperthyroidism and oxidative stress through the analysis of the redox profile of patients with subclinical hyperthyroidism exogenous (SCH) grade I (TSH = 0.1 to 0.4 IU/mL) and grade II (TSH < 0.1 IU/mL). Subjects and methods: We analyzed 46 patients with SCH due to the use of TSH suppressive therapy with LT4 after total thyroidectomy along with 6 control euthyroid individuals (3M and 3W). Patients were divided into two groups, G1 with TSH ≥ 0.1-0.4 IU/mL (n = 25; and 7M 14W) and G2 with TSH < 0.1 IU/mL (n = 25; and 4M 21W). Venous blood samples were collected to measure the levels of markers for oxidative damage (TBARS, FOX and protein carbonylation), muscle and liver damage (CK, AST, ALT, GGT) and antioxidants (GSH, GSSG and catalase). Results: Individuals in G2 showed a GSH/GSSG ratio ~ 30% greater than those in G1 (p = 0.004) and a catalase activity that was 4 times higher (p = 0.005). For lipid peroxidation, the levels measured in G2 were higher than both control and G1 (p = 0.05). No differences were observed for both protein carbonyl markers. G1 and G2 presented with greater indications of cell injury markers than the control group. Conclusion: TSH suppression therapy with LT4 that results in subclinical hyperthyroidism can cause a redox imbalance. The greater antioxidant capacity observed in the more suppressed group was not sufficient to avoid lipid peroxidation and cellular damage.

Inflammation and oxidative stress in heart failure: effects of exercise intensity and duration

Although acute exercise is apparently pro-inflammatory and increases oxidative stress, it can promote the necessary stress stimulus to train chronic adaptations in patients with chronic heart failure (CHF). This study aimed to compare the effects of exercise intensity and duration on the inflammatory markers soluble tumor necrosis factor receptor (sTNFR1) and interleukin-6 (IL-6), and on oxidative stress [malondialdehyde (MDA) and antioxidant enzymes: catalase (CAT) and superoxide dismutase (SOD)] in individuals with CHF. Eighteen patients performed three exercise sessions: 30 min of moderate-intensity (M30) exercise, 30 min of low-intensity (L30) exercise, and 45 min of low-intensity (L45) exercise. Blood analysis was performed before exercise (baseline), immediately after each session (after), and 1 h after the end of each session (1h after). Thirty min of M30 exercise promoted a larger stressor stimulus, both pro-inflammatory and pro-oxidative, than that promoted by exercises L30 and L45. This was evidenced by increased sTNFR1 and MDA levels after exercise M30. In response to this stressor stimulus, 1 h after exercise, there was an increase in IL-6 and CAT levels, and a return of sTNFR1 to baseline levels. These findings suggest that compared with the duration of exercise, the exercise intensity was an important factor of physiologic adjustments.

Erythrocyte oxidative stress markers in children with sickle cell disease / Marcadores de estresse oxidativo em eritrócitos de crianças com doença falciforme

Abstract Objective To determine eight parameters of oxidative stress markers in erythrocytes from children with sickle cell disease and compare with the same parameters in erythrocytes from healthy children, since oxidative stress plays an important role in the pathophysiology of sickle cell disease and because this disease is a serious public health problem in many countries. Methods Blood samples were obtained from 45 children with sickle cell disease (21 males and 24 females with a mean age of 9 years; range: 3–13 years) and 280 blood samples were obtained from children without hemoglobinopathies (137 males and 143 females with a mean age of 10 years; range: 8–11 years), as a control group. All blood samples were analyzed for methemoglobin, reduced glutathione, thiobarbituric acid reactive substances, percentage of hemolysis, reactive oxygen species, and activity of the enzymes glucose 6-phosphate dehydrogenase, superoxide dismutase, and catalase. Data were analyzed using Student's t-test and were expressed as the mean ± standard deviation. A p-value of <0.05 was considered significant. Results Significant differences were observed between children with sickle cell disease and the control group for the parameters methemoglobin, thiobarbituric acid reactive substances, hemolysis, glucose 6-phosphate dehydrogenase activity, and reactive oxygen species, with higher levels in the patients than in the controls. Conclusions Oxidative stress parameters in children's erythrocytes were determined using simple laboratory methods with small volumes of blood; these biomarkers can be useful to evaluate disease progression and outcomes in patients.

Resumo Objetivo Determinar parâmetros de estresse oxidativo em eritrócitos de crianças com doença falciforme e compará-los com os mesmos parâmetros em eritrócitos de crianças saudáveis, pois o estresse oxidativo desempenha um importante papel na fisiopatologia da doença falciforme, considerada um sério problema de saúde pública em muitos países. Métodos Foram obtidas amostras de sangue de 45 crianças com doença falciforme (21 meninos e 24 meninas com média de 9 anos, variação de 3 a 13) e 280 amostras de sangue de crianças sem hemoglobinopatias (137 meninos e 143 meninas com média de 10 anos, variação de 8 a 11), como grupo controle. Em todas as amostras foram determinados meta-hemoglobina, glutationa reduzida, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade das enzimas glucose6-fosfato desidrogenase, superóxido dismutase e catalase. Os dados foram analisados com o teste t de Student e foram expressos como média ± desvio padrão. Um valor de p < 0,05 foi considerado significativo. Resultados Foram observadas diferenças significativas entre as crianças com doença falciforme e o grupo controle para os parâmetros meta-hemoglobina, substâncias reativas ao ácido tiobarbitúrico, porcentagem de hemólise, espécies reativas de oxigênio e atividade da enzima glucose6-fosfato desidrogenase, com níveis aumentados nos pacientes. Conclusões Foi possível determinar parâmetros de estresse oxidativo em eritrócitos de crianças, com técnicas laboratoriais simples e pequenos volumes de sangue. Esses biomarcadores podem ser úteis na avaliação da progressão e dos resultados de tratamentos da doença.

Biochemical Markers of Oxidative Stress in Saudi Women with Recurrent Miscarriage

This study was undertaken to investigate the antioxidant/oxidant status in recurrent miscarriage patients. Antioxidants including glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR), reduced glutathione (GSH) and selenium (Se), as well as the oxidants hydrogen peroxide (H2O2), oxidised glutathione (GSSG) and lipid peroxidation were assayed in plasma, whole blood and placental tissue of non-pregnant women (NP), healthy pregnant women (HP), and recurrent miscarriage (RM) patients. Results indicated that all antioxidant activities and levels in plasma and whole blood of HP women were consistently moderately lower, and much more significantly lower in RM patients when both were compared to those seen in NP women (P<0.05 and P<0.001, respectively). Furthermore, whereas plasma antioxidant activities and levels were significantly lower in RM patients, those of whole blood and placental tissue were much more significantly lower when compared with HP women (P<0.001). Concurrent with these findings there were consistent increases of equal statistical significance and magnitude in the levels of all investigated oxidants assayed in all samples when compared in between subjects of the study as indicated above. Data thus illustrated a distinct shift in favor of oxidative reactions and reactive oxygen species (ROS) generation, and very significant decreases in the GSH/GSSG ratios in whole blood and placental tissue of RM patients when compared to HP and NP women (P<0.001). The above noted oxidative stress could have been a major causative factor of recurrent miscarriage.

The effect of weight reduction on antioxidant enzymes and their association with dietary intake of vitamins A, C and E / Efeito da redução de peso sobre as enzimas antioxidantes e associação destas com a ingestão de vitaminas A, C e E

Objective Our goal was to assess the effects of weight loss on antioxidant enzymes of red blood cells and it’s relation with vitamins A, E and C intake in 30 obese women. Subjects and methods General information, anthropometric measurements, 3-day food recall, and fasting blood samples were collected from 30 obese women at the beginning of the study and after 3 months intervention. Weight loss was set at about 10% of their weight before the intervention. Results Glutathione reductase and catalase activities showed a significant increase (P < 0.01) after weight reduction, but no significant changes were seen in the superoxide dismutase and glutathione peroxidase activities. There was a positive linear correlation between daily vitamin C intake with superoxide dismutase enzyme after intervention (P = 0.004, r = 0.507). There was a negative linear correlation between vitamin E intake and glutathione peroxidase activity before intervention (P = 0.005, r = -0.5). A negative correlation was found between daily vitamin A intake and glutathione reductase enzyme before and after intervention (r = -0.385, r = -0.397, P < 0.05) respectively. No significant correlation was observed between vitamins A, C, E amounts and catalase activity. Conclusions Ten percent weight reduction can have a significant role in increasing antioxidant enzymes activities, especially glutathione reductase, and catalase enzymes in obese women. However, it is important to take into consideration a balanced amount of certain nutrients while administering a diet with limited energy. .

Objetivo Nosso objetivo foi avaliar os efeitos da perda de peso sobre as enzimas antioxidantes de eritrócitos, e a relação destas com a ingestão das vitaminas A, E e C. Sujeitos e métodos Foram coletadas informações gerais e medidas antropométricas, registro alimentar de três dias e amostras de sangue em jejum de 30 mulheres obesas no início do estudo e depois de três meses da intervenção. A perda de peso determinada antes da intervenção foi de 10% do peso. Resultados As atividades da glutationa redutase e da catalase mostraram aumento significativo (P < 0,01) depois da perda de peso, mas não houve mudanças significativas nas atividades da superóxido dismutase e da glutationa peroxidase. Foi observada uma correlação linear positiva entre a ingestão diária de vitamina C e a enzima superóxido dismutase após a intervenção (P = 0,004, r = 0,507). Houve uma correlação linear negativa entre a ingestão de vitamina E e a atividade da glutationa peroxidase antes da intervenção (P = 0,005, r = -0,5). Foi observada uma correlação negativa entre a ingestão diária de vitamina A e a enzima glutationa redutase antes e depois da intervenção (r = -0,385, r = -0,397, P < 0,05), respectivamente. Não foram observadas correlações significativas entre as vitaminas A, C, E e os níveis e a atividade da catalase. Conclusões Uma redução de 10% no peso pode ter um papel significativo no aumento da atividade das enzimas antioxidantes, especialmente na glutationa redutase e catalase em mulheres obesas. Entretanto, é importante levar em consideração uma ingestão equilibrada de certos nutrientes ao se recomendar uma dieta com níveis de energia restritos. .

Nutraceutical preconditioning with arginine and oil mixes. Effects on inflammatory mediators, oxidative stress and lipid profile in patients undergoing radical prostatectomy

PURPOSE: To investigate whether there is any effect resulting from preconditioning with nutraceutical supplementation containing arginine and oil mixes with high ω9:ω6 ratio and low ω6:ω3 ratio containing EPA and DHA, ALA fatty acids on inflammatory mediators, antioxidant and lipid profile modulation in surgical trauma. METHODS: Twenty-six men scheduled for radical prostatectomy were randomized into three groups and treated as follows: Group 1 (skim milk, 0% fat), Group 2 (supplement with ω6:ω3 ratio of 8:1 and arginine) and Group 3 (supplement with high ω9:ω6 ratio of 3.2:1 and low ω6:ω3 ratio of 1.4:1 and arginine). Patients received skin milk or supplements twice a day (200 ml) during five days prior to surgery. Peripheral venous blood samples were collected at three different timepoints: five days before surgery (PRE), before anesthesia induction (IND) and on the 2nd postoperative day (POS). Parameters analyzed included inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α), antioxidants (catalase), lipid profile and heat shock protein (HSP-27). RESULTS: There were no significant differences between groups on inflammatory mediators and antioxidant parameters. However, lipid profile values (Cholesterol, LDL, Triglycerides, VLDL), were significantly different. CONCLUSION: Preconditioning with arginine and oil mixes containing high ω9:ω6 ratio and low ω6:ω3 ratio, has no effects on inflammatory mediators and oxidative stress in patients undergoing radical prostatectomy. Reduction of cholesterol, triglycerides, LDL and VLDL profiles may be related to the trauma effect. .

Protective effect of secondary plant metabolites from Ipomoea aquatica Forsk. against carbofuran induced damages.

Plausible interactions between food contaminants and natural constituents in vivo and protective effect of polyphenols present in I. aquatica against carbofuran toxicity in Charles Foster rats were evaluated. Determinations based on antioxidant enzyme activities showed significant alterations in glutathione, glutathione peroxidase, superoxide dismutase and catalase in tissues (liver and brain) and plasma of pesticide treated group while polyphenolic extracts from I. aquatica (IAE) attenuated their activities when given alongwith carbofuran. IAE decreased enhanced lipid peroxidation levels in plasma and erythrocyte membrane and cholesterol levels in brain and plasma. IAE also minimized histopathological degenerative changes produced by carbofuran. While single cell gel electrophoresis showed that secondary metabolites in leafy vegetables produced a combinatorial effect with pesticide at cellular level, DNA fragmentation level in bone marrow cells showed a decline in the IAE treated rats. Food safety adversely affected by various chemical contaminants can be retained by plant polyphenols and secondary plant constituents that can be found together in bolus. Therefore, the present study gives an insight into the protective role of naturally found polyphenols against pesticide toxicity.

Effect of newly isolated Lactobacillus ingluviei ADK10, from chicken intestinal tract on acetaminophen induced oxidative stress in Wistar rats.

The total antioxidative activity of L. ingluviei ADK10 isolated from chicken intestine intact cells and cell free culture supernatant (CFCS) was 54- 67.95%. The ability to scavenge a,a-Diphenyl-b-Picrylhydrazyl free radical ranged from 71 and 64% in intact cells and CFCS respectively. Total reducing activity of bacteria was equivalent to 290 µM/L of cysteine. Reducing glutathione activity was equivalent to 93.95µg/mL. Oral administration of the strain at a dose of 109 cfu/kg body weight to acetaminophen induced oxidative stress in rats increased catalase, glutathione and superoxide dismutase activity in the blood, liver and kidney and lowered malondialdehyde level. The results indicate that L. ingluviei ADK10 has potential free radical scavenging activity for the treatment of oxidative stress related disease.

Relationship between severity of adult community-acquired pneumonia and impairment of the antioxidant defense system

Oxidant/antioxidant imbalance has been reported in some infectious diseases, including community-acquired pneumonia (CAP). The aim was to assess the antioxidant status in adults with CAP and its relationship with clinical severity at admission. Fifty-nine patients with CAP were enrolled and categorized at admission by the FINE score, from July 2010 to October 2012. In the same period 61 controls were enrolled. Plasma samples were obtained at admission for determination of the ferric reducing ability of plasma (FRAP) and lipid peroxidation (8-isoprostane). Erythrocyte reduced (GSH)/oxidized (GSSG) glutathione, malondialdehyde (MDA) and antioxidant enzyme activity were assessed. Antioxidant status in adults with CAP represented by FRAP and the GSH/GSSG ratio were 16.8% (p=0.03) and 39.7% (p=0.04) lower than control values, respectively. In addition, FRAP values showed a positive correlation with GSH/GSSG ratio (r=0.852; p<0.02; n=59). The CAP group showed greater lipid peroxidation in both plasma and erythrocytes. The FINE score correlated negatively with FRAP (r= -0.718; p<0.05; n=59) and positively with MDA and F2 isoprostane levels (r=0.673; p<0.05; n=59; r=0.892; p<0.01; n=59, respectively). Antioxidant status alterations correlated with clinical severity. The FRAP assay and lipid peroxidation biomarkers may provide a useful parameter for estimating the severity and the clinical outcome of patients with CAP.

Acute effects of resistance exercise and intermittent intense aerobic exercise on blood cell count and oxidative stress in trained middle-aged women

The aim of this study was to compare the effect of an intermittent intense aerobic exercise session and a resistance exercise session on blood cell counts and oxidative stress parameters in middle-aged women. Thirty-four women were selected and divided into three groups: RE group (performing 60 min of resistance exercises, N = 12), spinning group (performing 60 min of spinning, N = 12), and control group (not exercising regularly, N = 10). In both exercise groups, lymphocytes and monocytes decreased after 1-h recuperation (post-exercise) compared to immediately after exercise (P < 0.05). Immediately after exercise, in both exercised groups, a significant increase in TBARS (from 16.5 ± 2 to 25 ± 2 for the spinning group and from 18.6 ± 1 to 28.2 ± 3 nmol MDA/mL serum for the RE group) and protein carbonyl (from 1.0 ± 0.3 to 1.6 ± 0.2 for the spinning group and from 0.9 ± 0.2 to 1.5 ± 0.2 nmol/mg protein for the RE group) was observed (P < 0.05). A decrease in antioxidant activities (non-protein sulfhydryl, superoxide dismutase, catalase) was also demonstrated with a negative correlation between damage markers and antioxidant body defenses (P < 0.05). These results indicate that an acute bout of intermittent or anaerobic exercise induces immune suppression and increases the production of reactive oxygen species, causing oxidative stress in middle-aged and trained women. Furthermore, we demonstrated that trained women show improved antioxidant capacity and lower oxidative damage than sedentary ones, demonstrating the benefits of chronic regular physical activity.

Serum adenosine deaminase, catalase and carbonic anhydrase activities in patients with bladder cancer

OBJECTIVES: The relationship between adenosine deaminase and various cancers has been investigated in several studies. However, serum adenosine deaminase activity and carbonic anhydrase and catalase activities in patients with bladder cancer have not previously been reported. Therefore, the aim of this study was to measure serum adenosine deaminase, carbonic anhydrase and catalase activities in patients with bladder cancer. MATERIALS AND METHODS: Forty patients with bladder cancer and 30 healthy controls were enrolled in the study. Serum adenosine deaminase, carbonic anhydrase and catalase activities were measured spectrophotometrically. RESULTS: Serum adenosine deaminase, carbonic anhydrase and catalase activities were significantly higher in patients with bladder cancer than controls (all significant, p<0.001). CONCLUSIONS: These markers might be a potentially important finding as an additional diagnostic biochemical tool for bladder cancer.

Antioxidant enzyme activity and malondialdehyde levels can be modulated by Piper betle, tocotrienol rich fraction and Chlorella vulgaris in aging C57BL/6 mice

OBJECTIVE: The aim of this study was to determine the erythrocyte antioxidant enzyme activity and the superoxide dismutase, catalase, glutathione peroxidase, and plasma malondialdehyde levels in aging mice and to evaluate how these measures are modulated by potential antioxidants, including the tocotrienol-rich fraction, Piper betle, and Chlorella vulgaris. METHOD: One hundred and twenty male C57BL/6 inbred mice were divided into three age groups: young (6 months old), middle-aged (12 months old), and old (18 months old). Each age group consisted of two control groups (distilled water and olive oil) and three treatment groups: Piper betle (50 mg/kg body weight), tocotrienol-rich fraction (30 mg/kg), and Chlorella vulgaris (50 mg/kg). The duration of treatment for all three age groups was two months. Blood was withdrawn from the orbital sinus to determine the antioxidant enzyme activity and the malondialdehyde level. RESULTS: Piper betle increased the activities of catalase, glutathione peroxidase, and superoxide dismutase in the young, middle, and old age groups, respectively, when compared to control. The tocotrienol-rich fraction decreased the superoxide dismutase activity in the middle and the old age groups but had no effect on catalase or glutathione peroxidase activity for all age groups. Chlorella vulgaris had no effect on superoxide dismutase activity for all age groups but increased glutathione peroxidase and decreased catalase activity in the middle and the young age groups, respectively. Chlorella vulgaris reduced lipid peroxidation (malondialdehyde levels) in all age groups, but no significant changes were observed with the tocotrienol-rich fraction and the Piper betle treatments. CONCLUSION: We found equivocal age-related changes in erythrocyte antioxidant enzyme activity when mice were treated with Piper betle, the tocotrienol-rich fraction, and Chlorella vulgaris. However, Piper betle treatment showed increased antioxidant enzymes activity during aging.

Relationship of Oxidative Stress in Hepatitis B Infection Activity with HBV DNA and Fibrosis

BACKGROUND: The aim of this study was to evaluate oxidative stress in various clinical forms of hepatitis B infection and to investigate its role in the development of the chronic form of the disease. METHODS: Ninety-three patients with inactive hepatitis B surface antigen (HbsAg) carrier state (IHBCS), 65 patients with chronic hepatitis B infection (CHB), and 42 healthy adults were included in the study. The following values were measured and compared in patient groups: total antioxidant status (TAS), total oxidative stress (TOS), oxidative stress index (OSI), sulfhydryl (SH), lipid peroxidation (LOOH), catalase (CAT), and ceruloplasmin. In patients with chronic hepatitis B, these values were compared with HBV DNA and fibrosis levels. RESULTS: ALT, TOS, LOOH, and OSI levels were higher in the CHB group compared to the other groups (P0.05). CONCLUSIONS: These finding suggested that oxidative stress is associated with hepatitis B activity.

Modelo experimental de infarto do miocárdio induzido por isoproterenol em ratos / Experimental model of myocardial infarction induced by isoproterenol in rats

OBJETIVO: Avaliar e validar, em nosso meio, o modelo de infarto do miocárdio induzido por isoproterenol em ratos por meio de análises de parâmetros hematológicos, bioquímicos, de marcadores do estresse oxidativo e histopatológicos. MÉTODOS: Trinta ratos jovens, machos, da linhagem Wistar (145 a 230 g), foram alocados aleatoriamente em dois grupos: grupo Simulado, submetido à falsa indução de infarto do miocárdio, e grupo Infarto, submetido à indução do infarto do miocárdio com isoproterenol. As aplicações, para indução do infarto, foram realizadas durante dois dias consecutivos, com intervalo de 24 horas entre elas. Após 24 horas da última aplicação, os ratos de ambos os grupos foram anestesiados e sacrificados para realização de coleta de sangue para hemograma e análise bioquímica (TGO, TGP, troponina I, ureia e creatinina) e coleta de fragmento do miocárdio para avaliação de marcadores do estresse oxidativo (atividade da catalase e concentração de glutationa) e exame histopatológico. RESULTADOS: Não houve mortalidade no grupo Simulado, enquanto a mortalidade no grupo Infarto foi de 25%. A indução do infarto do miocárdio com isoproterenol causou elevação das contagens de leucócitos e neutrófilos, dos níveis de TGO, troponina I e ureia, reduziu a atividade da catalase e os níveis teciduais de glutationa e causou alterações histopatológicas. Não acarretou alterações nas concentrações de hemoglobina, TGP e creatinina. CONCLUSÕES: O modelo de infarto do miocárdio induzido por isoproterenol em ratos foi adequadamente reproduzido em nosso laboratório, acarretando alterações em parâmetros hematológicos, bioquímicos, de marcadores de estresse oxidativo e histopatológicos.

OBJECTIVE: To evaluate and validate, in our laboratory, the essay of myocardial infarction induced by isoproterenol in rats by means of analysis of hematological, biochemical, oxidative stress markers and histopathological parameters. METHODS: Thirty young, male, Wistar rats (145 to 230 g) were randomly allocated in two groups: Sham group, which underwent a virtual myocardial infarction induction, and the Infarction group, which underwent a myocardial infarction induction with isoproterenol. The administrations for the infarction induction were performed during two consecutive days and a 24-hour interval between them. Twenty-four hours after the last administration, rats from both groups were anesthetized and sacrificed for blood sample collection to evaluate complete blood count (CBC) and biochemical parameters (SGOT, SGPT, troponin I, urea and creatinin), obtain myocardial fragments for oxidative stress markers analyses (catalase activity and glutathione concentrations) as well as histopathological examinations. RESULTS: There were no death cases in the Sham group, while the mortality rate in the Infarction group was 25%. Myocardial infarction induction with isoproterenol raised leukocytes and neutrophils counts, SGOT, troponin I and urea concentrations, reduced catalase enzyme activity and glutathione concentrations in the myocardium and let to histopathological concentrations as well. It did not exert alterations in terms of hemoglobin, SGPT and creatinin concentrations. CONCLUSIONS: The isoproterenol-induced myocardial infarction essay in rats was adequately reproduced in our laboratory, causing alterations in hematological, biochemical, oxidative stress markers and histopathological parameters.

Marcadores de desequilíbrio redox em sangue de pacientes hipertensos de uma comunidade no Nordeste do Brasil / Markers of redox imbalance in the blood of hypertensive patients of a community in Northeastern Brazil / Marcadores de desequilibrio en reacciones de reducción y oxidación en la sangre de pacientes hipertensos en una comunidad del Noreste del Brasil

FUNDAMENTO: Estudos recentes descrevem a participação de espécies reativas de oxigênio e nitrogênio na hipertensão. OBJETIVO: Identificar o desbalanço redox em sangue de hipertensos. MÉTODOS: Superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GPx), glutationa (GSH), vitamina C, transferrina, ceruloplasmina, malondialdeído (MDA) e o grupo carbonila, foram quantificados no sangue de 20 hipertensos e 21 controles. Os indivíduos tinham um Índice de Massa Corporal de > 18,5 e < 30 kg/m², glicemia < 100 mg/dL, colesterol sérico < 200 mg/dL, e eram mulheres não fumantes, não grávidas e não lactantes, não usuárias de alopurinol e probucol, e hipertensos em medicação anti-hipertensiva. Todos os indivíduos foram submetidos a um período preparatório de quatro semanas sem álcool, suplementos vitamínicos, dexametasona e paracetamol. RESULTADOS: Níveis reduzidos de CAT (p = 0,013), GSH ( p = 0,003) e MDA (p = 0,014), e altos níveis de GPx (p = 0,001) e ceruloplasmina (p = 0,015) foram obtidos no grupo de hipertensos, em comparação com os controles. Foi verificada uma correlação positiva entre a pressão sistólica e o MDA nos hipertensos e diastólica e CAT nos controles. CONCLUSÃO: Os dados obtidos são sugestivos de que os hipertensos apresentavam desequilíbrio em reações redox, a despeito do possível efeito atenuante de sua medicação anti-hipertensiva.

BACKGROUND: Recent studies describe the participation of reactive oxygen and nitrogen species in hypertension. OBJECTIVE: To identify the redox imbalance in the blood of hypertensive. METHODS: Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), vitamin C, transferrin, ceruloplasmin, malondialdehyde (MDA) and carbonyl group were quantified in the blood of 20 hypertensives and 21 controls. The individuals had a Body Mass Index of > 18.5 and < 30 kg/m², glycemia < 100 mg/dL, serum cholesterol < 200 mg/dL, and were nonsmokers, non-pregnant and non-lactating women, non-users of alopurinol and probucol, with hypertensives on antihypertensive medication. All individuals underwent a preparatory period of 4 weeks without alcohol, vitamin supplements, dexamethasone and paracetamol. RESULTS: Reduced levels of CAT (p 0.013), GSH (p 0.003) and MDA (p 0.014), and high levels of GPx (p 0.001) and ceruloplasmin (p 0.015) were obtained in the hypertensive group compared with controls. A positive correlation between systolic pressure and MDA in hypertensive and diastolic pressure and CAT in controls was obtained. CONCLUSION: The data obtained suggest that the hypertensives were in redox imbalance, despite the possibly attenuating effect of their antihypertensive medication.

FUNDAMENTO: Estudios recientes describen la participación de especies reactivas de oxígeno y nitrógeno en la hipertensión. OBJETIVO: Identificar el desequilíbrio redox em la sangre de los hipertensos MÉTODOS: El Superóxido dismutasa (SOD), catalasa (CAT), glutationa peroxidasa (GPx), glutationa (GSH), vitamina C, transferrina, ceruloplasmina, malondialdehído (MDA) y el grupo carbonilo, fueron cuantificados en la sangre de 20 hipertensos y 21 controles. Los individuos tenían un Índice de Masa Corporal de > 18,5 y < 30 kg/m², glicemia < 100 mg/dL, colesterol sérico < 200 mg/dL, y eran mujeres no fumadoras, no grávidas y no lactantes, no usuarias de alopurinol y probucol, con hipertensos sometidos a medicación antihipertensiva. Todos los individuos fueron sometidos a un período preparatorio de cuatro semanas sin alcohol, suplementos vitamínicos, dexametasona y paracetamol. RESULTADOS: Niveles reducidos de CAT (p = 0,013), GSH (p = 0,003) y MDA (p = 0,014), y altos niveles de GPx (p = 0,001) y ceruloplasmina (p = 0,015) fueron obtenidos en el grupo de hipertensos, en comparación con los controles. Fue obtenida una correlación positiva entre la presión sistólica y el MDA en la presión de hipertensos y diastólica y CAT en los controles. CONCLUSIÓN: Los datos obtenidos son sugestivos de que los hipertensos presentaban desequilibrio en reacciones de reducción y oxidación, a despecho del posible efecto atenuante de su medicación antihipertensiva.

Comparison of oxidative stress & leukocyte activation in patients with severe sepsis & burn injury.

Background & objectives: We evaluated pro- and anti-oxidant disturbances in sepsis and non-sepsis burn patients with systemic inflammatory response syndrome (SIRS). Adhesion molecules and inflammation markers on leukocytes were also analyzed. We hypothesized that oxidative stress and leukocyte activation markers can lead to the severity of sepsis. Methods: In 28 severe sepsis and 27 acute burn injury patients blood samples were collected at admission and 4 days consecutively. Oxidative stress markers: production of reactive oxygen species (ROS), myeloperoxidase, malondialdehyde and endogenous antioxidants: plasma protein sulphydryl groups, reduced glutathione, superoxide dismutase and catalase were measured. Flow cytometry was used to determine CD11a, CD14, CD18, CD49d and CD97 adhesion molecules on leukocytes. Procalcitonin, C-reactive protein, fibrinogen, platelet count and lactate were also analyzed. Results: Pro-oxidant parameters were significantly elevated in sepsis patients at admission, ROS intensity increased in burn patients until the 5th day. Endogenous antioxidant levels except catalase showed increased levels after burn trauma compared to sepsis. Elevated granulocyte activation and suppressed lymphocyte function were found at admission and early activation of granulocytes caused by increasing activation/migration markers in sepsis. Leukocyte adhesion molecule expression confirmed the suppressed lymphocyte and monocyte function in sepsis. Interpretation & conclusions: Severe sepsis is accompanied by oxidative stress and pathological leukocyte endothelial cell interactions. The laboratory parameters used for the evaluation of sepsis and several markers of pro- and antioxidant status were different between sepsis and non-sepsis burn patients. The tendency of changes in these parameters may refer to major oxidative stress in sepsis and developing SIRS in burns.

Assessment of lipid peroxidation and antioxidant status in rheumatoid arthritis and osteoarthritis patients

The aim of the present study was to assess the lipid peroxidation [LPO] and antioxidant status of patients with rheumatoid arthritis compared with osteoarthritis. This study included 30 RA, 30 OA patients and 15 healthy subjects. Parameters of activity of RA patients and clinical parameters of OA patients were assessed. Erythrocyte sedimentation rate [ESR], C reactive protein [CRP], serum malondialdehyde [MDA], the activities of erythrocyte superoxide dismutase [SOD] and catalase [CAT], glutathione [GSH] level, plasma glutathione-S-transferase [GST] activity and ceruloplasmin [Cp] level were measured. Increased MDA, plasma GST activity and Cp levels with reduction of the activities of SOD, CAT and GSH levels were demonstrated in RA and OA patients. A positive correlation was detected between the clinical and laboratory parameters in both RA and OA patients with GST and Cp. A direct correlation was found between previous parameters and serum MDA in RA. Meanwhile, a negative correlation was observed between these parameters with erythrocyte SOD, CAT activities and GSH level. Direct correlation also existed between MDA and GST with Cp, between erythrocyte SOD with CAT activities and negative correlations of GST activity with GSH level. Increased oxidative stress in RA and OA patients have led to compensatory changes in the levels of antioxidants. These changes provide additional protection against LPO. These findings confirm the role of oxidative stress in the pathogenesis of RA and OA, and that LPO markers and antioxidants can serve as surrogate markers for disease activity

Hypoglycemic and anti apoptotic effect of garlic in streptozotocin induced diabetic rats

Diabetes mellitus is caused by many factor include oxidative stress that leads to apoptosis of beta cells of the pancreas and so the antioxidant therapy strongly correlated with decrease risk of diabetes mellitus. The aim of the present study was to investigate the efficacy of an aqueous extract of raw garlic in controlling serum glucose, plasma c peptide of insulin, level of reduced glutathione and catalase activity in pancreatic tissue, also to estimate caspase 3 activity expression in pancreatic tissue in streptozotocin induced diabetic rats treated daily with garlic extract intraperitoneally [IP] for 6 weeks. This study was carried on 30 rats: grouped into 3 group. Group 1, the control normal group, was injected IP daily with 0.5 ml saline and group 2; diabetic group was injected with streptozotocin, 60 mg/Kg body weight [BWt] IP in 0.5 ml saline once and group 3; garlic-treated group, was injected IP daily with 500 mg/kg of the garlic extract 2 weeks before streptozotocin and 4 week after streptozotocin injection. There was a significant increase in blood glucose in streptozotocin group II [p = 0.001] as compared with control groups [331.3 +/- 16.15 vs 101.8 +/- 4.02 mg/dl] respectively and significantly decreased after treatment with garlic extract [161.5 +/- 5.28 mg/dl]. C peptide was significantly decreased in streptozotocin group II [p = 0.001] as compared with control groups [0.034 +/- 0.003 vs 0.053 +/- 0.001 ng/ml] respectively and significantly increased after treatment with garlic extract [0.046 +/- 0.003]. Catalase activity of pancreatic tissue was significantly decreased in streptozotocin group [p = 0.001] as compared with control groups [11.10 +/- 0.73 vs 25.7 +/- 0.55 U/gm tissue] respectively and significantly increased after treatment with garlic extract [20.3 +/- 0.66]. Reduced glutathione content of pancreatic tissue was significantly decreased in streptozotocin group [p = 0.001] as compared with control groups [0.67 +/- 0.055 vs 1.23 +/- 0.076 mg/g tissue] respectively and significantly increased after treatment with garlic extract [0.89 +/- 0.080 mg/g tissue]. Also it was observed that the expression of caspase 3 protein in the pancreatic tissue was decreased after garlic treatment using western blot technique. These results revealed that aqueous extract of raw garlic may have antioxidant and antiapoptotic activity that could be used in treatment of diabetes mellitus