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.

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.

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.

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.

Antithrombotic Effect of Oil from the Pulp of Bocaiúva-Acrocomia aculeata (Jacq.) Lodd. ex Mart. (Arecaceae).

The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 µg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production.

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.

Efficacy assessment of acid mine drainage treatment with coal mining waste using Allium cepa L. as a bioindicator.

The aim of this study was to evaluate the efficacy of the treatment of acid mine drainage (AMD) with calcinated coal mining waste using Allium cepa L. as a bioindicator. The pH values and the concentrations of aluminum, iron, manganese, zinc, copper, lead and sulfate were determined before and after the treatment of the AMD with calcinated coal mining waste. Allium cepa L. was exposed to untreated and treated AMD, as well as to mineral water as a negative control (NC). At the end of the exposure period, the inhibition of root growth was measured and the mean effective concentration (EC(50)) was determined. Oxidative stress biomarkers such as lipid peroxidation (TBARS), protein carbonyls (PC), catalase activity (CAT) and reduced glutathione levels (GSH) in the fleshy leaves of the bulb, as well as the DNA damage index (ID) in meristematic cells, were evaluated. The results indicated that the AMD treatment with calcinated coal mining waste resulted in an increase in the pH and an expressive removal of aluminum, iron, manganese and zinc. A high sub-chronic toxicity was observed when Allium cepa L. was exposed to the untreated AMD. However, after the treatment no toxicity was detected. Levels of TBARS and PC, CAT activity and the DNA damage index were significantly increased (P<0.05) in Allium cepa L. exposed to untreated AMD when compared to treated AMD and also to negative controls. No significant alteration in the GSH content was observed. In conclusion, the use of calcinated coal mining waste associated with toxicological tests on Allium cepa L. represents an alternative system for the treatment and biomonitoring of these types of environmental contaminants.

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.

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.

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.

Textile effluents induce biomarkers of acute toxicity, oxidative stress, and genotoxicity.

The present work consists of a comparative evaluation of the toxicity of a nonremediated textile effluent (NRTE) with an effluent remediated by a pulverized chitosan system (RCTS) or by a conventional effluent process (remediated biologic and physico-chemical effluent [RBPC]). Acute toxicity assays, oxidative stress biomarkers, physico-chemical parameters, and genotoxicity indices were analyzed to achieve the toxicity of all effluents. After RCTS treatment, approximately 80% of dyes were removed, together with a significant decreased of the metal content, compared with a relatively increase in metal content after RBPC treatment. RBPC and RCTS treatments did not cause acute toxicity to Vibrio fischeri and Artemia sp., whereas RBPC caused acute toxicity to Daphnia magna but RCTS did not. Compared with NRTE, chitosan remediation decreased oxidative stress biomarkers, such as the contents of lipoperoxidation (measured as thiobarbituric acid-reactive substances [TBARS], 29.9%) and the reduced form of glutathione (GSH; 73.5%) levels in D. rerio, whereas animals exposed to RBPC showed enhanced TBARS (57.2%) and decreased GSH concentrations (56.4%). RCTS and RBPC remediation elicited catalase activity induction (161.8% and 127.3%, respectively) compared with NRTE. Accordingly, DNA fragmentation and micronucleus frequency in D. rerio decreased after remediation with RBPC or RCTS compared with NRTE, but RCTS treatment was more effective than RBPC in decreasing genotoxicity (90.5% and 73.8% decrease in DNA fragmentation and 67.8% and 50.4% decrease in micronucleus frequency, respectively). The results indicate that chitosan adsorption system is a useful tool for textile effluent remediation compared with the conventional remediation by biologic and physico-chemical processes.

Reactive oxygen species, antioxidants and fish mitochondria.

In fishes, irrespective of their thermoregulatory capacity or metabolic rate, the main physiological source of reactive oxygen species (ROS) is mitochondria. During active swimming, ROS is by an large provided by red muscle mitochondria. Other tissues such as lens, liver, heart, swimbladder, roe and blood also afford important ROS production and antioxidant levels in resting fish. A close relationship between structure and function is evident in fish mitochondrion with a surface-to-volume optimization by the size of cristae to maximize electron transfer. The mechanism of fish mitochondrial superoxide anion (O2*-) and ROS production as well as the mechanism of mitochondrial coupling and proton leak seems similar to that of mammals. Contrary to mammalian red cells, fish erythrocytes possess nuclei and mitochondria. The presence of cardiolipin and the absence of cholesterol in fish mitochondrial membranes confer a high structural flexibility. The difference in phospholipid unsaturation may explain the greater proton leak in endotherms compared to thermoconformers. The present review summarizes our current understanding in respect to comparative aspects of fish mitochondrial function, with an emphasis on the adaptations to changes in temperature, O2 availability and O2 consumption, which are generally coupled to changes in antioxidant status and ROS production. Nevertheless, most work on this fascinating area has yet to be done. The literature on the effect of xenobiotics, aquatic contamination, and aquaculture issues are not reviewed. Data on the production of NO and reactive nitrogen species (RNS), on O2 sensing and on the role of ROS and RNS in cell signalling involving fish mitochondria are almost completely lacking in the literature.

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.

Aqueous extract of Ilex paraguariensis attenuates the progression of atherosclerosis in cholesterol-fed rabbits.

Ilex paraguariensis aqueous extract (mate) is an antioxidant-rich beverage widely consumed in South American countries. Here we questioned whether mate could reduce the progression of atherosclerosis in 1% cholesterol-fed rabbits. New Zealand White male rabbits (n = 32) were divided into four groups: control (C, n = 5), control-mate (CM, n = 5), hypercholesterolemic (HC, n = 11) and hypercholesterolemic-mate (HCM, n = 11). The daily water and mate extract consumption was approximately 400 ml. After 2 months of treatment, mate intake did not change the lipid profile or hepatic cholesterol content of control or hypercholesterolemic rabbits (p < 0.05). However, the atherosclerotic lesion area was considerably smaller in the hypercholesterolemic-mate group (HCM, 35.4% vs. HC, 60.1%; p < 0.05). In addition, the aortic cholesterol content was around half that of the HC group (HCM, 36.8 vs. HC, 73.9 microg/mg of protein, p < 0.05). In spite of this, the thiobarbituric acid-reactive substances (TBARS) in the atherosclerotic aorta, liver and serum, and the activity of the antioxidant enzymes in liver and aorta did not differ among groups (p > 0.05). The results showed that Ilex paraguariensis extract can inhibit the progression of atherosclerosis in cholesterol-fed rabbits, although it did not decrease the serum cholesterol or aortic TBARS and antioxidant enzymes.

A comparative study of albendazole and mebendazole-induced, time-dependent oxidative stress.

Albendazole (ABZ) and mebendazole (MBZ) are two benzimidazole-derived drugs that show remarkable antihelmintic activity and are widely used in the treatment and control of helminths. Some antihelmintic drugs seem to act through the deleterious generation of reactive oxygen and nitrogen species (ROS and RNS, respectively) to which helminths have no, or relatively low, antioxidant defences (AD), when compared to aerobic organisms. The main objective of the present study consisted of the evaluation of the effect of both drugs on the AD and on some oxidative stress indicators in the host liver. Adult, male, Wistar rats were treated with ABZ or MBZ at doses of 40 mg/kg for different periods of time (2, 4, 8 and 10 days). After treatment, the activities of superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase, as well as the concentrations of TBARS, reduced glutathione, oxidized glutathione and total glutathione, were evaluated in rat hepatocytes. The serum nitrogen monoxide, usually known as nitric oxide (NO) levels, was also measured. The results showed that both drugs provoked an oxidative stress condition, demonstrated through the elevation of TBARS contents and through the decrease of some AD. Moreover, ABZ showed to be a strong ROS and RNS generator while MBZ showed a low and transient effect on ROS generation. It is suggested that MBZ could be the first-choice drug in the treatment of helminthiasis because it shares a similar therapeutic indication with ABZ, and because it causes only a mild oxidative stress to the host.

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.

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.