Biomarkers of oxidative stress and inflammation in subjects with COVID-19: Characterization and prognosis of the disease.

Coronavirus disease (COVID-19) is an acute respiratory disease caused by the new coronavirus (SARS-CoV-2) that has spread throughout the world causing millions of deaths. COVID-19 promotes excessive release of pro-inflammatory cytokines leading to acute lung injury and death. Reactive oxygen species (ROS) and oxidative stress (OS) may also play a role in the pathophysiology of COVID-19. The present study investigated levels of inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12) and OS biomarkers (MPO, SOD, CAT, GST enzymes and contents of GSH, TBARS and PC) in patients with SARS-CoV-2 infection, which were correlated with disease severity. Patients with SARS significantly increased IL-1ß levels, while IL-6 levels were elevated in both groups of SARS-CoV-2 positive patients. The most severe patients showed increased levels of IL-8 and IL-10, while subjects without SARS showed lower values. MPO activity were higher in both groups of SARS-CoV-2 positive patients, while SOD and CAT activity were decreased in both groups. Compared to controls, GGT was elevated only in the SARS patient group, while GST values were increased in the group of positive patients in SARS-CoV-2 without SARS and were decreased in patients with SARS. GSH and UA contents decreased in SARS-CoV-2 positive subjects, whereas TBARS and PC contents increased in both groups of SARS-CoV-2 positive patients, particularly in the SARS patient group. In addition, several important correlations were found between cytokines and the different OS parameters suggesting some inter-relationship in the complex antioxidant system of the patients. In general, patients with SARS-CoV-2 infection showed higher levels of OS biomarkers, and also elevated contents of IL-6 and IL-10, probably worsening the damage caused by SARS-CoV-2 infection. This damage may contribute to the severity of the disease and its complications, as well as a prognosis for SARS-CoV-2 patients.

Systemic oxidative stress in children with cystic fibrosis with bacterial infection including Pseudomonas Aeruginosa.

INTRODUCTION: Oxidative stress (OS) occurs in cystic fibrosis (CF). OBJECTIVE: The objective of this work is to evaluate the influence of bacterial infection on biomarkers of OS (catalase [CAT], glutathione peroxidade [GPx], reduced glutathione [GSH]), markers of oxidative damage (protein carbonyls [PC], thiobarbituric acid reactive substances [TBARS]), together with the nutritional status and lung function in children with CF. METHODS: Cross-sectional study including CF group (CFG, n = 55) and control group (CG, n = 31), median age: 3.89 and 4.62 years, respectively. CFG was distributed into CFG negative bacteriology (CFGB-, n = 27) or CFG positive bacteriology (CFGB+, n = 28), and CFG negative Pseudomonas aeruginosa (CFGPa-, n = 36) or CFG positive Pseudomonas aeruginosa (CFGPa+, n = 19). RESULTS: Compared with CG, CFG (P = .034) and CFGB+ (P = .042) had lower body mass index-for-age z-score; forced expiratory volume in the first second was lower in CFGB+ and CFGPa+ (both P < .001). After adjusting for confounders and compared with CG: CFG showed higher TBARS (P ≤ .001) and PC (P = .048), and lower CAT (P = .004) and GPx (P = .003); the increase in PC levels was observed in CFGB+ (P = .011) and CFGPa+ (P = .001) but not in CFGB- (P = .510) and CFGPa- (P = .460). CONCLUSIONS: These results indicate a systemic OS in children with CF. The presence of bacterial infection particularly Pseudomonas aeruginosa seems to be determinant to exacerbate the oxidative damage to proteins, in which PC may be a useful biomarker of OS in CF.

Neuroprotective Effects of Acrocomia aculeata Pulp Oil Microcapsules on Rats Subjected to Chronic Stress.

Acrocomia aculeata fruits are rich in monounsaturated fatty acid, ß-carotene, tocopherol, and other antioxidant compounds. The aim of our study was to investigate and compare the protective effects of A. aculeata pulp oil and microencapsulated pulp oil on brain oxidative damage induced by chronic restraint stress (CRS) in rats (cortex, hippocampus, and striatum). Thirty-six Wistar rats were divided into six treatment groups: C, P, and M groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively. The SC, SP, and SM groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively, and were then subjected to uninterrupted 6 h of CRS. After 21 days of testing, the rats were euthanized and the brain tissue of the groups was removed for evaluation for oxidative damage markers and antioxidant enzymes. Endpoints of oxidative stress (OS) markers (lipid peroxidation, protein carbonylation, and reduced glutathione [GSH]) and antioxidant enzymes (superoxide dismutase and catalase) were evaluated. By imposing chronic stress on rats, pulp oil and microcapsules of pulp oil induced positive antioxidant responses, mainly by increasing the GSH content, increasing the ability of neural tissues to deal with inherent OS, thus protecting against neurodegenerative diseases. The administration of A. aculeata pulp oil and microencapsulated pulp oil made the reversal of the oxidant parameters, which may protect the brain tissue of rats altered by CRS. The Clinical Trial Registration number: n° 1.008/2018 CEUA/UFMS.

DNA damage, oxidative stress, and inflammation in children with celiac disease.

The objective of this study was to evaluate the level of genomic instability in patients with celiac disease and to establish a relationship between inflammation, oxidative stress, and DNA damage in these patients. Myeloperoxidase (MPO) activity, adenosine deaminase, nitric oxide (NOx), thiobarbituric acid, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and DNA damage were evaluated in peripheral blood samples from 47 celiac disease patients and 31 controls. Patients with celiac disease presented higher levels of DNA damage in comparison to controls (p=0.023). This difference was also observed for markers of oxidative stress, such as CAT (p=0.011) and SOD (p=0.013), and inflammatory markers such as MPO (p < 0.001) and NOx (p=0.009). Positive correlations were found between DNA damage levels and the values of CAT (r=0.405; p=0.009) and SOD (r=0.516; p < 0.001). Positive correlations were also found between GPx and NOx (r=0.349; p=0.030) and MPO and NOx (r=0.239; p=0.039). CAT and NOx showed a negative correlation (r= -0.315; p=0.042). In conclusion, intestinal inflammation can have systemic effects, causing an imbalance between oxidant and antioxidant markers, which may promote increased levels of DNA damage.

Effect of RYGB on Oxidative Stress in Adults: a 6-Year Follow-up Study.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is effective for weight loss but may have long-term effects on markers of oxidative stress (OS). The objective of this study is to evaluate the effect of bariatric surgery with RYGB on OS blood markers in a 72-month period after surgery. METHODS: A prospective cohort study was conducted with 20 patients before and after RYGB (months M0, M6, M12, M24, and M72) compared with a control group of 35 adults assessed only once. RESULTS: The body mass index (BMI) (45.71 ± 6.97 kg/m2) decreased by 38% from M0 to M24 (17.51 ± 5.50 kg/m2, p < 0.001), followed by a 12% increase from M24 to M72 (p < 0.001). Serum concentrations of vitamin E (adjusted for total cholesterol and triglycerides) and vitamin C increased throughout the study (p < 0.001). ß-carotene levels decreased progressively through to M72 (p = 0.008). Reduced glutathione (GSH) content and catalase (CAT) activity decreased at M6, M12, and M24, but no differences were found at M72 compared with M0. Concentrations of thiobarbituric acid reactive substances (TBARS) were lower M12 and M24 in comparison with baseline values (p < 0.001 and p = 0.004, respectively) but were similar to baseline values at 72 months (p = 0.114). CONCLUSIONS: GSH content, TBARS concentrations, and CAT activity returned to baseline values 72 months after RYGB, indicating the persistence of systemic OS, possibly attributable to weight regain and/or changes in the antioxidant defenses, such as the reduction in ß-carotene levels.

Seasonal and ontogenetic changes modulate oxygen consumption and antioxidant defenses in the cutlassfish Trichiurus lepturus (Pisces, Trichiuridae).

Several oxidative stress markers and liver oxygen consumption were measured in different tissues of the marine fish Trichiurus lepturus in late summer and late winter, as well as in juveniles and adult females. Oxygen consumption in liver, superoxide dismutase (SOD) and catalase (CAT) activity in liver, red cells, lens and roe, vitamin E, ubiquinol10, ß-carotene in liver, red cells, and roe, as well as contents of reduced glutathione (GSH) and lipoperoxidation (TBARS) in red cells were evaluated. Regarding ontogeny, compared to adult fish, juveniles showed significant higher SOD activity in liver and lens, as well as higher liver contents of vitamin E. In contrast, adult females showed higher contents of vitamin E in roe, ubiquinol10 in liver and roe, and higher GSH levels in red cells, while the other markers remained unchanged. Regarding seasonal changes, no differences were detected in adult females for liver CAT and ubiquinol10, CAT in roe, vitamin E in roe and in red cells, liver and red cell ubiquinol10, and in GSH in red cells. However, and coinciding with the spawning period of late summer, liver oxygen consumption, SOD and CAT activity and ubiquinol10 contents in roe and SOD activity in red cells, and red cell TBARS contents were higher compared to late winter. These temporal antioxidant adjustments of Trichiurus lepturus seem to be parallel to the higher oxygen consumption typical of juvenile forms and also to the intense spawning and foraging activities of adult females in late summer.

Chronic Melatonin Administration Reduced Oxidative Damage and Cellular Senescence in the Hippocampus of a Mouse Model of Down Syndrome.

Previous studies have demonstrated that melatonin administration improves spatial learning and memory and hippocampal long-term potentiation in the adult Ts65Dn (TS) mouse, a model of Down syndrome (DS). This functional benefit of melatonin was accompanied by protection from cholinergic neurodegeneration and the attenuation of several hippocampal neuromorphological alterations in TS mice. Because oxidative stress contributes to the progression of cognitive deficits and neurodegeneration in DS, this study evaluates the antioxidant effects of melatonin in the brains of TS mice. Melatonin was administered to TS and control mice from 6 to 12 months of age and its effects on the oxidative state and levels of cellular senescence were evaluated. Melatonin treatment induced antioxidant and antiaging effects in the hippocampus of adult TS mice. Although melatonin administration did not regulate the activities of the main antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase) in the cortex or hippocampus, melatonin decreased protein and lipid oxidative damage by reducing the thiobarbituric acid reactive substances (TBARS) and protein carbonyls (PC) levels in the TS hippocampus due to its ability to act as a free radical scavenger. Consistent with this reduction in oxidative stress, melatonin also decreased hippocampal senescence in TS animals by normalizing the density of senescence-associated ß-galactosidase positive cells in the hippocampus. These results showed that this treatment attenuated the oxidative damage and cellular senescence in the brain of TS mice and support the use of melatonin as a potential therapeutic agent for age-related cognitive deficits and neurodegeneration in adults with DS.

Aerobic and anaerobic training sessions promote antioxidant changes in young male soccer players / Efeito sobre o estresse oxidativo promovido por sessões de treinamento aeróbico comparativamente a sessões anaeróbicas em jogadores juvenis brasileiros de futebol

OBJECTIVE: The aim of this study was to investigate the effect of aerobic vs. anaerobic intense training sessions on biomarkers of oxidative stress. METHODS: The included sample comprised 18 junior male soccer players (18-21 years) during the intermediate season. Blood samples were obtained before (baseline) and after aerobic or anaerobic training sessions and the following substances were assayed: (i) the biomarkers of cellular damage Thiobarbituric Acid-Reactive Substances and Oxidized Glutathione; (ii) the non-enzymatic antioxidants Reduced Glutathione and Total-Glutathione, (iii) the antioxidant enzymes Superoxide Dismutase, Catalase, Glutathione Reductase, Glutathione Peroxidase and Glutathione S-Transferase. RESULTS: (a) the contents of Thiobarbituric Acid-Reactive Substances and Oxidized Glutathione showed no significant differences before vs. after aerobic or anaerobic training sessions. (b) After aerobic training sessions, the activity of Superoxide Dismutase, Glutathione Reductase, and the contents of Reduced Glutathione and Total Glutathione were decreased; the activity of Glutathione S-transferase and Glutathione Peroxidase were increased while Catalase activity remained unaltered. (c) After anaerobic training sessions, Catalase activity decreased; Glutathione-Peroxidase increased; Superoxide Dismutase, Glutathione Reductase, and Reduced, Oxidized and Total Glutathione showed no significant differences. CONCLUSION: These results provide evidence of a more pronounced systemic oxidative stress after the aerobic as compared to the anaerobic training session in young soccer players.

OBJETIVO: Investigar o efeito no estresse oxidativo promovido por sessão de treinamento aeróbico comparativamente à sessão anaeróbica em jogadores de futebol juvenis. MÉTODOS: Amostras de sangue de 18 jogadores de futebol juvenis (idade entre 18-21 anos) foram utilizadas. Estas amostras foram obtidas imediatamente antes e após um conjunto de sessão de treinamentoaeróbico comparativamente ao de sessão anaeróbica e biomarcadores de dano celular como conteúdos de Substâncias Reativas a Ácido Tiobarbitúrico (TBARS) no plasma, os conteúdos de defesas antioxidantes nãoenzimáticas como a Glutationa Reduzida, Glutationa Oxidada, e Glutationa Total, bem como as atividades de enzimas antioxidantes como Superóxido Dismutase, Catalase, Glutationa Redutase, Glutationa Peroxidase e Glutationa S-Transferase foram avaliadas. RESULTADOS: Os conteúdos de TBARS e Glutationa Oxidada não apresentaram diferenças significativas na comparação entre ambas as sessões. Entretanto, após a sessão de treinamento aeróbico, as atividades da Superóxido Dismutase e Glutationa Redutase, bem como os conteúdos de Glutationa Reduzida e Glutationa Total mostraram diminuições significativas, enquanto que as atividades da Glutationa S-Transferase e Glutationa Peroxidase foram aumentadas e as da Catalase não mostraram diferenças. Por outro lado, após a sessão de treinamento anaeróbico, a atividade da Catalase reduziu-se, a da Glutationa Peroxidase foi significativamente aumentada, enquanto que as da Superóxido Dismutase e Glutationa Reductase, assim como os conteúdos de Glutationa Reduzida, Glutationa Oxidada e Glutationa Total não se alteraram significativamente. CONCLUSÃO: Os resultados evidenciam um estresse oxidativo sistêmico mais acentuado após a sessão de treinamento aeróbico comparativamente à sessão anaeróbica em jogadores de futebol juvenis.

Impact of the Use of Benznidazole Followed by Antioxidant Supplementation in the Prevalence of Ventricular Arrhythmias in Patients With Chronic Chagas Disease: Pilot Study.

Patients with chronic Chagas disease have a higher prevalence of premature ventricular contraction (PVC) because of immunoinflammatory response magnified by the increased oxidative stress. Thus, the sequential treatment with benznidazole (BZN) and antioxidants can reduce the prevalence of PVC. We wish to establish whether the etiological treatment of Chagas disease followed by supplementation with the antioxidant vitamins E and C decreases the prevalence of PVC in these patients. A sample of 41 patients with chronic Chagas disease at different stages of the heart disease was selected for the treatment against the causative agent using BZN (5 mg·kg·d, minimum dose 300 mg daily) for 2 months followed by supplementation with antioxidants such as vitamins E (800 UI/d) and C (500 mg/d) for 6 months. The prevalence of PVC was observed by conducting 24-hour Holter. To evaluate the oxidative status of the patients, serum markers of oxidative stress like glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase were measured, and also reduced glutathione, vitamin E, and markers of tissue damage like thiobarbituric acid reactive substances and protein carbonyl. A decrease in the prevalence of PVC in patients with advanced Chagas heart disease was observed (5391 vs. 1185, P = 0.0068). This reduction was followed by decrease of serum markers of oxidative stress. In patients with a lower degree of cardiac damage, the reduction on prevalence of PVC was not significant. The etiological treatment with BZN followed by supplementation with antioxidant vitamins E and C reduces episodes of PVC in patients with severe Chagas heart disease.

Influence of inflammatory response, infection, and pulmonary function in cystic fibrosis.

AIMS: Recurrent infections and activation of the inflammatory response affect the prognosis of cystic fibrosis (CF). We investigated the relationship between inflammatory response, infection, and pulmonary function in CF. MAIN METHODS: A clinical-cross-sectional study was conducted with 86 subjects: control group (CG, n=31, the same age and sex of the CF group), and CF group (CFG, n=55, age: 1-16 years), further distributed into CFG negative or positive bacteriology (CFGB(-)/CFGB(+)), and CFG negative or positive Pseudomonas aeruginosa (CFGPa(-)/CFGPa(+)). Using the Wald test, multiple linear regression (95% confidence interval) was performed between CG and CFG, and between CG and each of the CF subgroups (CFGB(-)/CFGB(+) and CFGPa(-)/CFGPa(+)). The inflammatory markers evaluated were myeloperoxidase (MPO), adenosine deaminase (ADA) activities, interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), nitric oxide metabolites (NOx) levels, and total and differential leukocyte counts. KEY FINDINGS: After adjusting for sex and age, CFG compared to CG revealed an increase of MPO, IL-1ß (P<0.001 in all subgroups), and CRP: CFG (P=0.002), CFGB(-) (P=0.007), CFGB(+) (P=0.009), CFGPa(-) (P=0.004) and CFGPa(+) (P=0.020). NOx (P=0.001, P<0.001), leukocytes (P=0.002, P=0.001), and neutrophils (P=0.003, P<0.001) were increased in CFGB(+) and CFGPa(+), respectively. A negative correlation between FEV1 and leukocytes (P=0.008) and FEV1 and neutrophils (P=0.031) resulted in CFG. SIGNIFICANCE: The inflammatory response characterized by the increase of MPO, IL-1ß, and CRP is determinant for CF. Also leukocytosis due to neutrophilia determines the pulmonary function deficiency in this disease.

Antioxidant intervention attenuates oxidative stress in children and teenagers with Down syndrome.

We previously demonstrated that systemic oxidative stress is present in Down syndrome (DS) patients. In the present study we investigated the antioxidant status in the peripheral blood of DS children and teenagers comparing such status before and after an antioxidant supplementation. Oxidative stress biomarkers were evaluated in the blood of DS patients (n=21) before and after a daily antioxidant intervention (vitamin E 400mg, C 500 mg) during 6 months. Healthy children (n=18) without DS were recruited as control group. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), gamma-glutamyltransferase (GGT), glucose-6-phosphate dehydrogenase (G6PD) and myeloperoxidase (MPO), as well as the contents of reduced glutathione (GSH), uric acid, vitamin E, thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC) were measured. Before the antioxidant therapy, DS patients presented decreased GST activity and GSH depletion; elevated SOD, CAT, GR, GGT and MPO activities; increased uric acid levels; while GPx and G6PD activities as well as vitamin E and TBARS levels were unaltered. After the antioxidant supplementation, SOD, CAT, GPx, GR, GGT and MPO activities were downregulated, while TBARS contents were strongly decreased in DS. Also, the antioxidant therapy did not change G6PD and GST activities as well as uric acid and PC levels, while it significantly increased GSH and vitamin E levels in DS patients. Our results clearly demonstrate that the antioxidant intervention with vitamins E and C attenuated the systemic oxidative damage present in DS patients.

O carvedilol potencializa o efeito antioxidante das vitaminas E e C na cardiopatia chagásica crônica / Carvedilol enhances the antioxidant effect of vitamins E and C in chronic chagas heart disease

FUNDAMENTO: A doença de Chagas continua a ser uma importante doença endêmica no país, sendo o acometimento cardíaco a sua manifestação mais grave. OBJETIVO: Verificar se o uso concomitante de carvedilol potencializará o efeito antioxidante das vitaminas E e C na atenuação do estresse oxidativo sistêmico na cardiopatia chagásica crônica. MÉTODOS: Foram estudados 42 pacientes com cardiopatia chagásica, agrupados de acordo com a classificação modificada de Los Andes, em quatro grupos: 10 pacientes no grupo IA (eletrocardiograma e ecocardiograma normais: sem envolvimento do coração), 20 pacientes do grupo IB (eletrocardiograma normal e ecocardiograma anormal: ligeiro envolvimento cardíaco), oito pacientes no grupo II (eletrocardiograma e ecocardiograma anormais, sem insuficiência cardíaca: moderado envolvimento cardíaco) e quatro pacientes no grupo III (eletrocardiograma e ecocardiograma anormais com insuficiência cardíaca: grave envolvimento cardíaco). Os marcadores de estresse oxidativo foram medidos no sangue, antes e após um período de seis meses de tratamento com carvedilol e após seis meses de terapia combinada com vitaminas E e C. Os marcadores foram: atividades da superóxido dismutase, catalase, glutationa peroxidase, glutationa S-transferase e redutase, mieloperoxidase e adenosina deaminase, e os níveis de glutationa reduzida, de espécies reativas do ácido tiobarbitúrico, proteína carbonilada, vitamina E e óxido nítrico. RESULTADOS: Após o tratamento com carvedilol, todos os grupos apresentaram diminuições significativas dos níveis de proteína carbonilada e glutationa reduzida, enquanto os níveis de óxido nítrico e atividade da adenosina aumentaram significativamente apenas no grupo menos acometido (IA). Além disso, a maioria das enzimas antioxidantes mostrou atividades diminuídas nos grupos menos acometidos (IA e IB). Com a adição das vitaminas ao carvedilol houve diminuição dos danos em proteínas, nos níveis de glutationa e na maior parte da atividade das enzimas antioxidantes. CONCLUSÕES: A queda dos níveis de estresse oxidativo, verificada pelos marcadores testados, foi mais acentuada quando da associação do fármaco carvedilol com as vitaminas antioxidantes. Os dados sugerem que tanto o carvedilol isoladamente como sua associação com as vitaminas foram eficazes em atenuar o dano oxidativo sistêmico em pacientes com CC, especialmente aqueles menos acometidos, sugerindo a possibilidade de sinergismo entre esses compostos.

BACKGROUND: Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. OBJECTIVE: To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. METHODS: A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. RESULTS: After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. CONCLUSIONS: The decrease in oxidative stress levels observed by means of the markers tested was more significant when carvedilol was used in combination with the antioxidant vitamins. The findings suggest that both carvedilol alone and in combination with the vitamins were effective in attenuating the systemic oxidative stress in patients with Chagas heart disease, especially those less severely affected, thus suggesting the possibility of synergism between these compounds.

Systemic oxidative stress in children and teenagers with Down syndrome.

AIMS: The aim of this study was to evaluate the antioxidant status and oxidative stress biomarkers in the blood of children and teenagers with Down syndrome. MAIN METHODS: The analysis of enzymatic antioxidant defenses, such as the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST), non-enzymatic antioxidants, such as levels of reduced glutathione (GSH), uric acid (UA) and vitamin E, as well as oxidative damage indicators, such as protein carbonyls (PC) levels and lipoperoxidation (TBARS), of DS individuals (n=20) compared to healthy controls (n=18). Except the vitamin E was measured by HPLC, all other markers were measured spectrophotometrically. KEY FINDINGS: Antioxidant enzymes analysis showed significant increases in the SOD (47.2%), CAT (24.7%) and GR (49.6%) activities in DS subjects. No significant difference in GPx activity was detected while GST activity (61.2%) was decreased, and both responses may be consequence of the depletion of GSH (24.9%) levels. There were no significant differences in TBARS levels, while PC levels showed decreased (31.7%) levels compared to healthy controls, which may be related to the increase (16.1%) found in serum UA. Levels of vitamin E showed no significant differences between DS individuals compared to controls. SIGNIFICANCE: The results revealed a systemic pro-oxidant status in DS individuals, evidenced by the increased activity of some important antioxidant enzymes, together with decreased GSH levels in whole blood and elevated UA levels in plasma, probably as an antioxidant compensation related to the redox imbalance in DS individuals.

Carvedilol enhances the antioxidant effect of vitamins E and C in chronic Chagas heart disease.

BACKGROUND: Chagas disease is still an important endemic disease in Brazil, and the cardiac involvement is its more severe manifestation. OBJECTIVE: To verify whether the concomitant use of carvedilol will enhance the antioxidant effect of vitamins E and C in reducing the systemic oxidative stress in chronic Chagas heart disease. METHODS: A total of 42 patients with Chagas heart disease were studied. They were divided into four groups according to the modified Los Andes classification: 10 patients in group IA (normal electrocardiogram and echocardiogram; no cardiac involvement); 20 patients in group IB (normal electrocardiogram and abnormal echocardiogram; mild cardiac involvement); eight patients in group II (abnormal electrocardiogram and echocardiogram; no heart failure; moderate cardiac involvement); and four patients in group III (abnormal electrocardiogram and echocardiogram with heart failure; severe cardiac involvement). Blood levels of markers of oxidative stress were determined before and after a six-month period of treatment with carvedilol, and six months after combined therapy of carvedilol with vitamins E and C. The markers analyzed were as follows: activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and reductase, myeloperoxidade and adenosine deaminase; and the levels of reduced glutathione, thiobarbituric-acid reactive substances, protein carbonyls, vitamin E, and nitric oxide. RESULTS: After treatment with carvedilol, all groups showed significant decrease in protein carbonyls and reduced glutathione levels, whereas nitric oxide levels and adenosine activity increased significantly only in the less severely affected group (IA). In addition, the activity of most of the antioxidant enzymes was decreased in the less severely affected groups (IA and IB). By combining the vitamins with carvedilol, a reduction in protein damage, in glutathione levels, and in the activity of most of the antioxidant enzymes were observed. CONCLUSIONS: The decrease in oxidative stress levels observed by means of the markers tested was more significant when carvedilol was used in combination with the antioxidant vitamins. The findings suggest that both carvedilol alone and in combination with the vitamins were effective in attenuating the systemic oxidative stress in patients with Chagas heart disease, especially those less severely affected, thus suggesting the possibility of synergism between these compounds.

Roundup disrupts male reproductive functions by triggering calcium-mediated cell death in rat testis and Sertoli cells.

Glyphosate is the primary active constituent of the commercial pesticide Roundup. The present results show that acute Roundup exposure at low doses (36 ppm, 0.036 g/L) for 30 min induces oxidative stress and activates multiple stress-response pathways leading to Sertoli cell death in prepubertal rat testis. The pesticide increased intracellular Ca(2+) concentration by opening L-type voltage-dependent Ca(2+) channels as well as endoplasmic reticulum IP3 and ryanodine receptors, leading to Ca(2+) overload within the cells, which set off oxidative stress and necrotic cell death. Similarly, 30 min incubation of testis with glyphosate alone (36 ppm) also increased (45)Ca(2+) uptake. These events were prevented by the antioxidants Trolox and ascorbic acid. Activated protein kinase C, phosphatidylinositol 3-kinase, and the mitogen-activated protein kinases such as ERK1/2 and p38MAPK play a role in eliciting Ca(2+) influx and cell death. Roundup decreased the levels of reduced glutathione (GSH) and increased the amounts of thiobarbituric acid-reactive species (TBARS) and protein carbonyls. Also, exposure to glyphosate-Roundup stimulated the activity of glutathione peroxidase, glutathione reductase, glutathione S-transferase, γ-glutamyltransferase, catalase, superoxide dismutase, and glucose-6-phosphate dehydrogenase, supporting downregulated GSH levels. Glyphosate has been described as an endocrine disruptor affecting the male reproductive system; however, the molecular basis of its toxicity remains to be clarified. We propose that Roundup toxicity, implicated in Ca(2+) overload, cell signaling misregulation, stress response of the endoplasmic reticulum, and/or depleted antioxidant defenses, could contribute to Sertoli cell disruption in spermatogenesis that could have an impact on male fertility.

Oxidative stress markers in adults 2 years after Roux-en-Y gastric bypass.

INTRODUCTION: Obesity is a chronic disease associated with oxidative stress. Bariatric surgery for the treatment of obesity may affect biomarkers of oxidative stress. OBJECTIVES: The aim of the present study was to evaluate the effect of Roux-en-Y gastric bypass (RYGB) on blood markers of oxidative stress, such as vitamins C and E, ß-carotene, reduced glutathione (GSH), catalase (CAT), ferric reducing antioxidant potential (FRAP), and thiobarbituric acid-reactive substances (TBARS). METHODS: A prospective controlled clinical trial was carried out. The participants were distributed into two groups: a control group (n=35), which was evaluated once, and a bariatric group (n=35), which was evaluated at baseline as well as 6, 12, and 24 months after surgery. RESULTS: After surgery, the BMI decreased from 47.05±1.46 to 30.53±1.14 kg/m (P<0.001), but 25.7% of the participants regained weight after 24 months. In relation to the baseline, postsurgery reductions were found in vitamin C (31.9±4.6%, P<0.001), ß-carotene (360.7±368.3%, P<0.001), vitamin E (22.8±4.1%, P<0.001), GSH (6.6±5.2%, P=0.090), CAT (12.7±5.6%, P=0.029), and FRAP (1.2±3.8%, P=0.085) 2 years after RYGB. TBARS levels decreased after 12 months (71.6±2.9%, P<0.001) in relation to the baseline but increased by 195.0±28.2% between the 12th and the 24th month (P<0.001). CONCLUSION: The present findings show that oxidative stress returned 2 years after RYGB. Concentrations of vitamin C, ß-carotene, GSH, CAT, and FRAP were decreased, whereas the concentration of TBARS decreased in the first year but increased in the following year, which may be partly explained by the imbalance between antioxidants and pro-oxidants.

Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis.

Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na(3)VO(4)) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na(3)VO(4) was cytotoxic against T24 cells (EC(50)=5.8 µM at 24 h), but in the presence of ascorbate (100 µM) the EC(50) fell to 3.3 µM. Na(3)VO(4) plus ascorbate caused a strong inhibition of cell proliferation (up to 20%) and increased the generation of ROS (4-fold). Na(3)VO(4) did not directly cleave plasmid DNA, at this aspect no synergism was found occurring between Na(3)VO(4) and ascorbate once the resulting action of the combination was no greater than that of both substances administered separately. Cells from Ehrlich ascites carcinoma-bearing mice were used to determine the activity of antioxidant enzymes, the extent of the oxidative damage and the type of cell death. Na(3)VO(4) alone, or combined with ascorbate, increased catalase activity, but only Na(3)VO(4) plus ascorbate increased superoxide dismutase activity (up to 4-fold). Oxidative damage on proteins and lipids was higher due to the treatment done with Na(3)VO(4) plus ascorbate (2-3-fold). Ascorbate potentiated apoptosis in tumor cells from mice treated with Na(3)VO(4). The results indicate that pharmacological doses of ascorbate enhance the generation of ROS induced by Na(3)VO(4) in tumor cells causing inhibition of proliferation and apoptosis. Apoptosis induced by orthovanadate and ascorbate is closer related to inhibition on Bcl-xL and activation of Bax. Our data apparently rule out a mechanism of cell demise p53-dependent or related to Cdk2 impairment.

La complementación con antioxidantes atenúa el estrés oxidativo en pacientes con hepatitis C crónica / Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients

Resumen La generación excesiva de especies reactivas de oxígeno está implicada en la patogénesis de la hepatitis C. El objetivo de este estudio fue evaluar el estado antioxidante de la sangre en pacientes infectados por VHC tratados o sin tratamiento con la terapia estándar, antes y después de la complementación con vitaminas E, C y Zinc. Se evaluaron los biomarcadores de estrés oxidativo en sangre de tres grupos de pacientes: grupo 1 - controles, grupo 2 - pacientes con VHC sin tratamiento examinados antes y después de una complementación diaria de antioxidantes (800mg de vitamina E, 500mg de vit. C, y 40mg de zinc) durante 6 meses y grupo 3 - pacientes con VHC tratados con interferón pegilado combinado con ribavirina, también examinados antes y después de la misma complementación diaria con antioxidantes. Antes del tratamiento antiviral los pacientes con VHC mostraban una mayor actividad del superóxido dismutasa, la catalasa y el glutatión peroxidasa y una actividad reducida de la glutatión reductasa, (..) (AU)

Abstract Reactive oxygen species (ROS) overgeneration is involved in the pathogenesis of hepatitis C. The aim of this study was to evaluate the antioxidant status in the blood of HCV infected patients treated or not with standard therapy before and after supplementation of vitamins E, C and zinc. Biomarkers of oxidative stress were evaluated in the blood of three groups of patients: group 1 - controls; group 2 - HCV patients without treatment examined before and after a daily antioxidant supplementation (vitamin E 800mg, C 500mg and zinc 40mg) for 6 months; and group 3 - HCV patients treated with pegylated interferon combined with ribavirin, also examined before and after the same antioxidant supplementation. Before antiviral treatment HCV patients showed enhanced superoxide dismutase, catalase and glutathione peroxidase activities and decreased glutathione reductase activity, while lipoperoxidation was increased and reduced glutathione showed decreased levels compared to controls. Treatment with standard therapy enhanced the activities of catalase and glutathione S-transferase, increased contents of protein carbonyl and promoted further reduced glutathione depletion. After antioxidant supplementation, decreased catalase and glutathione S-transferase activities, decreased lipoperoxidation in group 2, and increased reduced glutathione contents in both supplemented groups were detected. Before antioxidant supplementation, alanine aminotransferase and gamma glutamyl transferase contents showed significant increases in group 2. Conclusion: Untreated HCV patients and also those treated with the standard therapy are coping with a systemic oxidative stress. The antioxidant supplementation conferred an antioxidant protection to both supplemented groups attenuating oxidation processes related to the disease (AU)

Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients.

UNLABELLED: Reactive oxygen species (ROS) overgeneration is involved in the pathogenesis of hepatitis C. The aim of this study was to evaluate the antioxidant status in the blood of HCV infected patients treated or not with standard therapy before and after supplementation of vitamins E, C and zinc. Biomarkers of oxidative stress were evaluated in the blood of three groups of patients: group 1 - controls; group 2 - HCV patients without treatment examined before and after a daily antioxidant supplementation (vitamin E 800 mg, C 500 mg and zinc 40 mg) for 6 months; and group 3 - HCV patients treated with pegylated interferon combined with ribavirin, also examined before and after the same antioxidant supplementation. Before antiviral treatment HCV patients showed enhanced superoxide dismutase, catalase and glutathione peroxidase activities and decreased glutathione reductase activity, while lipoperoxidation was increased and reduced glutathione showed decreased levels compared to controls. Treatment with standard therapy enhanced the activities of catalase and glutathione S-transferase, increased contents of protein carbonyl and promoted further reduced glutathione depletion. After antioxidant supplementation, decreased catalase and glutathione S-transferase activities, decreased lipoperoxidation in group 2, and increased reduced glutathione contents in both supplemented groups were detected. Before antioxidant supplementation, alanine aminotransferase and gamma glutamyl transferase contents showed significant increases in group 2. CONCLUSION: Untreated HCV patients and also those treated with the standard therapy are coping with a systemic oxidative stress. The antioxidant supplementation conferred an antioxidant protection to both supplemented groups attenuating oxidation processes related to the disease.