Alteration in systemic markers of oxidative and antioxidative status in Tunisian patients with asthma: relationships with clinical severity and airflow limitation

Objective: This study aims to determine the systemic oxidant-antioxidant status in Tunisian patients with asthma. Methods: We evaluated the levels of malondialdehyde (MDA) as thiobarbituric acid complexes, total protein carbonyls (PCs) and advanced oxidation protein products (AOPP). The levels of total thiols, protein sulfhydryls, glutathione (GSH), together with hydrogen peroxide, ascorbic acid, iron and total antioxidant status (TAS) were colorimetrically estimated. Glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities were assessed in plasma and erythrocytes by spectrophotometry. We also determined the levels of nitric oxide (NO) and peroxynitrite in plasma from asthmatic patients and healthy controls. The volume of fractionated exhaled NO (Fe_NO) was evaluated by the Medisoft HypAir method. Estimation of DNA damage was determined using the comet assay. Results: Asthmatic patients showed increased levels of MDA in comparison to healthy controls (p?<?0.001), while no significant difference was found in protein carbonyls (p?=?0.79) and AOPP (p?=?0.98). Patients with asthma also had significantly lower levels of total thiols (355.9?±?15.72 versus 667.9?±?22.65, p?<?0.001), protein sulfhydryls (333.99?±?16.41 versus 591.95?±?24.28, p?<?0.001) and glutathione (p?<?0.001). They also showed decreased GSH-Px activity (p?<?0.001), whereas no significant differences in measurements of catalase and SOD enzyme activities were observed between the two groups (respectively, p?=?0.06 and p?=?0.55). In addition, ascorbic acid and nitric oxide levels were decreased in asthmatics in comparison to controls (p?<?0.01). Conclusions: Our findings highlight that oxidative stress and defective anti-oxidative status are major alterations in Tunisian patients with asthma.     

Persistence of protein oxidation products and plasma antioxidants in juvenile idiopathic arthritis. A one-year follow-up study

OBJECTIVE: Plasma protein oxidation products and blood antioxidants, like superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) were investigated in children with juvenile idiopathic arthritis (JIA) in a year follow-up study. METHODS: Carbonyl group content within plasma proteins, activity of red blood cell SOD and GPx, as well as the blood TAS level were determined in 14 children with JIA twice, namely at the admission to the hospital (Time 0 = T0) and then after a year of treatment (Time 1 = T1). RESULTS: An increased level of plasma protein carbonyls was observed in both assessments (T0 and T1) as compared to control. However there was no significant difference in plasma carbonyls level between the initial (T0) and final (T1) examination of the patients. Similarly, SOD activity was higher in children with JIA as compared to control subjects and did not change significantly after a year of follow-up. Red blood cell GPx activity remained within the normal range throughout the study. Interestingly, the blood TAS level was initially comparable to control and rose significantly after the year of treatment. CONCLUSION: A level of plasma protein oxidation products remains significantly higher in children with JIA as compared to healthy subjects. The lack of accumulation of plasma protein carbonyls may result from efficient proteolysis in childhood and/or adaptive increase of the blood TAS level in the course of effective anti-inflammatory therapy. Analysis of plasma oxidative stress markers and antioxidant potential of the blood might be helpful in monitoring the clinical treatment of children suffering from JIA.     

MnSOD overexpression prevents liver mitochondrial DNA depletion after an alcohol binge but worsens this effect after prolonged alcohol consumption in mice

Both acute and chronic alcohol consumption increase reactive oxygen species (ROS) formation and lipid peroxidation, whose products damage hepatic mitochondrial DNA (mtDNA). To test whether manganese superoxide dismutase (MnSOD) overexpression modulates acute and chronic alcohol-induced mtDNA lesions, transgenic MnSOD-overexpressing (TgMnSOD(+++)) mice and wild-type (WT) mice were treated by alcohol, either chronically (7 weeks in drinking water) or acutely (single intragastric dose of 5 g/kg). Acute alcohol administration increased mitochondrial ROS formation, decreased mitochondrial glutathione, depleted and damaged mtDNA, durably increased inducible nitric oxide synthase (NOS) expression, plasma nitrites/nitrates and the nitration of tyrosine residues in complex V proteins and decreased complex V activity in WT mice. These effects were prevented in TgMnSOD(+++) mice. In acutely alcoholized WT mice, mtDNA depletion was prevented by tempol, a superoxide scavenger, L-NAME and 1400W, two NOS inhibitors, or uric acid, a peroxynitrite scavenger. In contrast, chronic alcohol consumption decreased cytosolic glutathione and increased hepatic iron, lipid peroxidation products and respiratory complex I protein carbonyls only in ethanol-treated TgMnSOD(+++) mice but not in WT mice. In chronic ethanol-fed TgMnSOD(+++) mice, but not WT mice, mtDNA was damaged and depleted, and the iron chelator, deferoxamine (DFO), prevented this effect. In conclusion, MnSOD overexpression prevents mtDNA depletion after an acute alcohol binge but aggravates this effect after prolonged alcohol consumption, which selectively triggers iron accumulation in TgMnSOD(+++) mice but not in WT mice. In the model of acute alcohol binge, the protective effects of MnSOD, tempol, NOS inhibitors and uric acid suggested a role of the superoxide anion reacting with NO to form mtDNA-damaging peroxynitrite. In the model of prolonged ethanol consumption, the protective effects of DFO suggested the role of iron reacting with hydrogen peroxide to form mtDNA-damaging hydroxyl radical.     

Serum levels of zinc, copper and selenium in patients with Wilson's disease treated with zinc

Zinc administered on a long-term basis in excess to patients with Wilson a disease blocks in a significant way copper absorption from the gut, prevents its accumulation and toxic action in the organism. The authors investigated the effect of its long-term administration on the plasma concentration of copper, zinc, and selenium, on the superoxide dismutase activity in red blood cells and glutathione peroxidase activity in whole blood. In seven patients with Wilson a disease treated with zinc sulphate, 136 mg of elemental zinc for 1.5 years (18 months), the authors assessed the plasma concentration of zinc, copper, selenium and ceruloplasmin, the activity of superoxide dismutase in red blood cells, the activity of glutathione peroxidase in whole blood and the urinary excretion of zinc and copper in 24 hours. Envisaged findings with regard to the diagnosis of the investigated patients and their treatment: elevated plasma zinc concentration and increased urinary excretion, reduced copper and ceruloplasmin plasma concentration and increased urinary copper excretion. The authors recorded also a significantly elevated selenium plasma concentration and a significantly higher concentration of superoxide dismutase in red blood cells (p < 0.05). The increase of the glutathione peroxidase activity in whole blood in the investigated patients was not significant (p < 0.05). Changes in the values of the investigated parameters in patients with Wilson s disease treated on a long-term basis with zinc indicate the possible mutual interaction of zinc with other trace elements with an impact on the activity of the corresponding metalloenzymes, i.e. in the sphere in antioxidant systems.     

Reactive oxidant species in asthma

PURPOSE OF REVIEW: This overview summarizes some recent studies on the balance of oxidants to antioxidants in patients with asthma. The aim of the review is to compare studies on the changes in oxidants/antioxidants in stable asthma or in acute exacerbation of asthma. RECENT FINDINGS: Our review of the recent literature in this field seems to indicate conflicting findings. Increased release of reactive oxygen species such as superoxide anion and hydrogen peroxide has been reported in exhaled breath condensates and from circulating granulocytes, and from the bronchoalveolar lavage cells of patients with asthma. In asthma, bronchial obstruction is associated with an increased spontaneous and stimulus-induced production of oxygen free radicals. The primary defense against reactive oxygen species is endogenous antioxidants, which are found to be altered in asthma. A marked decrease in plasma antioxidant capacity occurs. Superoxide dismutase activity is higher in erythrocytes and serum of asthmatic than in normal subjects and is diminished in cells from lavage and brushing samples of patients with asthma. Higher level of erythrocyte catalase activity has only been found in Chinese asthmatic patients while decreased glutathione peroxidase activity has been well documented. SUMMARY: Since there are considerable discrepancies in erythrocyte or plasma antioxidant enzyme activity in patients with asthma, the problem at this time is attempting to sort out these conflicting results and to find their roles in the pathogenesis of asthma. There is good evidence that antioxidant compounds may have a potential role in the treatment of asthma, especially of asthma exacerbation.     

Antioxidant effect of N-acetylcysteine on prehepatic portal hypertensive gastropathy in rats

Background. Portal hypertension is a clinical syndrome associated with the development of a hyperdynamic circulation and gastroesophageal varices.Aim. To evaluate the antioxidant effect of N-acetylcysteine on portal hypertensive rats.Material and methods. Portal hypertension was induced by partial portal vein ligation (PPVL). Oxidative damage in the stomach was measured by lipoperoxidation trough thiobarbituric acid reactive substances (TBARS) and antioxidant enzyme activity; we also evaluated nitrates and nitrites level and histology stained by hematoxylin-eosin. We performed evaluation of portal pressure and measurement of vessels diameter. Liver damage was evaluated by measuring hepatic enzymes. The animals were divided in four experimental groups (n = 6): Sham-operated (SO), SO + NAC, Partial portal vein ligation (PPVL) and PPVL + NAC. N-acetylcysteine (10 mg/kg ip) was administered daily for 7 days and started 8 days after surgery.Results. The portal hypertensive group showed an increase in portal pressure, vessels diameter, levels of TBARS and nitrates and nitrites when compared to SO group. These values were accompanied by a decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzyme activity. Histology showed dilated vessels in the gastric mucosa in the PPVL group. NAC was able to decrease portal pressure values, vessels diameter, TBARS and also nitrates and nitrites levels when compared to PPVL group. Furthermore, PPVL+NAC group presented an increase in SOD and GPx activity. N-acetylcysteine attenuated damage in gastric mucosa.Conclusion. Oxidative stress is associated with portal hypertension and that antioxidant NAC is able to minimize damages of PPVL in rats.     

Modulation of antioxidant status in streptozotocin-induced diabetic male wistar rats following intake of red palm oil and/or rooibos

Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.     

Time course study of oxidative and nitrosative stress and antioxidant enzymes in K2Cr2O7-induced nephrotoxicity

Background

It has been established that hypothyroidism protects rats against renal ischemia and reperfusion (IR) oxidative damage. However, it is not clear if hypothyroidism is able to prevent protein tyrosine nitration, an index of nitrosative stress, induced by IR or if antioxidant enzymes have involved in this protective effect. In this work it was explored if hypothyroidism is able to prevent the increase in nitrosative and oxidative stress induced by IR. In addition the activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase was studied. Control and thyroidectomized (HTX) rats were studied 24 h of reperfusion after 60 min ischemia.

Methods

Male Wistar rats weighing 380 ± 22 g were subjected to surgical thyroidectomy. Rats were studied 15 days after surgery. Euthyroid sham-operated rats were used as controls (CT). Both groups of rats underwent a right kidney nephrectomy and suffered a 60 min left renal ischemia with 24 h of reperfusion. Rats were divided in four groups: CT, HTX, IR and HTX+IR. Rats were sacrificed and samples of plasma and kidney were obtained. Blood urea nitrogen (BUN) and creatinine were measured in blood plasma. Kidney damage was evaluated by histological analysis. Oxidative stress was measured by immunohistochemical localization of protein carbonyls and 4-hydroxy-2-nonenal modified proteins. The protein carbonyl content was measured using antibodies against dinitrophenol (DNP)-modified proteins. Nitrosative stress was measured by immunohistochemical analysis of 3-nitrotyrosine modified proteins. The activity of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase was measured by spectrophotometric methods. Multiple comparisons were performed with ANOVA followed by Bonferroni t test.

Results

The histological damage and the rise in plasma creatinine and BUN induced by IR were significantly lower in HTX+IR group. The increase in protein carbonyls and in 3-nitrotyrosine and 4-hydroxy-2-nonenal modified proteins was prevented in HTX+IR group. IR-induced decrease in renal antioxidant enzymes was essentially not prevented by HTX in HTX+IR group.

Conclusion

Hypothyroidism was able to prevent not only oxidative but also nitrosative stress induced by IR. In addition, the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase seem not to play a protective role in this experimental model.     

Accumulation of oxidative damage during replicative aging of the yeast Saccharomyces cerevisiae

Comparison of senescent yeast obtained by the "baby machine" technique with 2-day-old stationary phase cells revealed decreased activities of glutathione reductase, glutathione S-transferase, glutathione peroxidase and alcohol dehydrogenase, reduction of total antioxidant capacity, protein glycation and accumulation of products of oxidative damage: protein carbonyls and DNA damage assessed by augmented content of 8-oxoguanine and increased tail momentum of cellular DNA in the comet assay. These results are consistent with a role for oxidative damage during replicative senescence of Saccharomyces cerevisiae.     

Oxidative stress in juvenile essential hypertension

OBJECTIVE: Oxidative stress, an antioxidant/pro-oxidant imbalance, in patients with juvenile essential hypertension was measured via several biochemical parameters. As the blood pressure is associated with the body mass index (BMI), results were compared with those on BMI-matched controls. DESIGN AND SETTING: A prospective observational study at a university teaching hospital. PATIENTS: Children and adolescents with essential hypertension (mean standard deviation: age 14.4 +/- 3.1 years, BMI 25.0 +/- 6.9 kg/m(2), n = 52) before any treatment, and controls with a similar BMI distribution (age 14.3 +/- 4.3 years, BMI 24.4 +/- 6.6 kg/m(2), n = 48). METHODS: Measurements were made of the plasma levels of (1) nitrites + nitrates, an indirect measure of available nitric oxide; (2) lipid peroxidation end-products, as malondialdehydes and free thiols; and (3) the redox status of the red blood cell glutathione, as a new oxidative stress parameter. RESULTS: There were decreased plasma levels of nitrates and increased levels of lipid peroxidation end-products in the hypertensive patients, resulting in a consistent increase in the plasma lipid peroxidation/nitric oxide ratio as compared with the controls with the same BMI (P <0.01). This ratio additionally correlated directly with both the systolic and diastolic blood pressures for the overall patient population (P <0.001). A significant glutathione depletion in the red blood cells resulted in an elevated ratio of oxidized/reduced forms with a reduced antioxidant protective capacity in the hypertensive patients versus the BMI-matched controls (P <0.001). CONCLUSIONS: The presence of systemic oxidative stress was proven in hypertensive children and adolescents, irrespective of their BMI.     

Muscle antioxidant status in chronic alcoholism

BACKGROUND Chronic myopathy due to excessive ethanol intake is one of the most frequent causes of acquired skeletal myopathy in developed countries. Its pathogenesis is multi-factorial, only partially clarified, and antioxidant imbalance has been suggested to influence its development, being a type II glucolytic, fast-twitch fiber subset more sensitive to this effect. METHODS: We assessed superoxide dismutase, glutathione peroxidase, and glutathione reductase enzyme activities as well as the total antioxidant status capacity in muscle samples obtained from 41 chronic alcoholic males and 12 age-matched controls. Alcoholic skeletal myopathy was defined according to standard histologic criteria. We evaluated the influence of ethanol consumption, caloric and protein nutritional status, and the presence of skeletal myopathy with the tissue activities of these antioxidant enzymes. RESULTS: Chronic alcoholics showed a 16% reduction in glutathione peroxidase and a 13% increase of superoxide dismutase in the skeletal muscle, compared with controls (p < 0.05, both). Muscle antioxidant changes in chronic alcoholics were not related to the presence of skeletal myopathy, parameters of alcohol consumption, or conventional nutritional parameters. CONCLUSIONS: Antioxidant muscle enzyme activities are partially disturbed in chronic alcoholism, although not related to the presence of myopathy, amount of ethanol consumed, or the nutritional status of the patients. Further studies should assess other aspects not included in the present study such as muscle site-specific changes in antioxidant status/oxidative damage, specific fiber-type sensitivity to alcohol, and type and quantity of antioxidant content of the diet or in the alcohol beverages.     

Antioxidant status in asthma

Reduced levels of glutathione peroxidase (GSH-Px) have been observed in adults with asthma. This study examines the antioxidant status in children with asthma compared with a control group in a cross-sectional analysis. Red blood cell GSH-Px, superoxide dismutase (SOD), and plasma concentrations of retinol, vitamin C, alpha tocopherol, and cholesterol were measured in 37 subjects (26 males) with stable controlled asthma. Thirty-five subjects (20 males) without eczema, hayfever, or recurrent respiratory symptoms were used as a control group. Children with asthma had significantly reduced red blood cell GSH-Px activity compared with controls [median (inter-quartile range) for asthma group, 10.25 (9.25–11.91)]; for control group, 11.75 (10.34–12.26) IU/g Hb; P = 0.0061. There were no significant differences in activity of SOD or vitamin C, retinol, or alpha tocopherol/cholesterol ratio. The reduction in GSH-Px activity may have therapeutic and etiological implications for asthma. The effects of disease activity and treatment on antioxidant status needs for further study. Pediatr Pulmonol. 1994; 18:34–38. © 1994 Wiley-Liss. Inc.     

Effects of N-acetylcysteine on the lung histopathology and oxidant-antioxidant status in rabbits exposed to cigarette smoke

We aimed to evaluate the effects of smoking on the histopathology and the oxidant-antioxidant status of lungs and to test the effects of N-acetylcysteine (NAC) on the induced changes. Rabbits were exposed to cigarette smoke (CS) in a glass chamber for one hour daily for one month. An NAC control group was given intraperitoneal NAC only. CS + NAC rats were exposed to smoke and given intraperitoneal NAC. A control group was exposed to clean air only. At the end of one month, animals were sacrificed and lung tissues were examined histopathologically. Blood levels of protein sulfhydryls, carbonyls, prostaglandin F(2alpha) (PGF(2alpha)) and malondialdehyde (MDA) were measured. Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar and bronchial lumen, alveolar destruction, emphysematous changes and bronchoalveolar hemorrhage scores were significantly increased in rabbits exposed to CS compared with the control group. Protein sulfhydryls were significantly decreased; carbonyls, PGF(2alpha) and MDA levels were significantly increased in the smoke exposed rabbits. Administration of NAC to rabbits exposed to CS caused a reduction in the bronchoalveolar hemorrhage score and blood PGF(2alpha) levels. Other parameters were unaffected by NAC. Exposure to CS causes severe histopathological changes and negatively effects the oxidant-antioxidant status in the lungs of rabbits. A low daily dose of NAC has some ameliorative effects on histopathological changes and oxidant-antioxidant status of the lungs in smoke exposed rabbits.     

High glucose mediates pro-oxidant and antioxidant enzyme activities in coronary endothelial cells

AIM: Excess levels of free radicals such as nitric oxide (NO) and superoxide anion (O(2)(-)) are associated with the pathogenesis of endothelial cell dysfunction in diabetes mellitus. This study was designed to investigate the underlying causes of oxidative stress in coronary microvascular endothelial cells (CMECs) exposed to hyperglycaemia. METHODS: CMECs were cultured under normal (5.5 mmol/l) or high glucose (22 mmol/l) concentrations for 7 days. The activity and expression (protein level) of endothelial NO synthase (eNOS), inducible NOS (iNOS), NAD(p)H oxidase and antioxidant enzymes, namely, superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) were investigated by specific activity assays and Western analyses, respectively, while the effects of hyperglycaemia on nitrite and O(2)(-) generation were investigated by Griess reaction and cytochrome C reduction assay, respectively. RESULTS: Hyperglycaemia did not alter eNOS or iNOS protein expressions and overall nitrite generation, an index of NO production. However, it significantly reduced the levels of intracellular antioxidant glutathione by 50% (p < 0.05) and increased the protein expressions and activities of p22-phox, a membrane-bound component of pro-oxidant NAD(p)H oxidase and antioxidant enzymes (p < 0.05). Free radical scavengers, namely, Tiron and mercaptopropionylglycine (MPG) (0.1-1 micromol/l) reduced hyperglycaemia-induced antioxidant enzyme activity and increased glutathione and nitrite generation to the levels observed in CMEC cultured in normoglycaemic medium (p < 0.01). The differences in enzyme activity and expressions were independent of the increased osmolarity generated by high glucose levels as investigated by using equimolar concentrations of mannitol in parallel experiments. CONCLUSIONS: These results suggest that hyperglycaemia-induced oxidative stress may arise in CMEC as a result of enhanced pro-oxidant enzyme activity and diminished generation of antioxidant glutathione. By increasing the antioxidant enzyme capacity, CMEC may protect themselves against free radical-induced cell damage in diabetic conditions.     

Age-associated oxidative macromolecular damages in rat brain regions: role of glutathione monoester

The generation of reactive oxygen species (ROS) and resultant oxidative stress has been implicated in the mechanism of brain dysfunction due to age-related neurodegenerative diseases. We have evaluated the efficacy of glutathione monoester (GME) when administered intraperitoneally (12 mg/kg body weight) for 20 days on glutathione, ROS, superoxide anion production, lipid peroxidation (LPO), protein carbonyls, thiol status, oxidative DNA damage products such as 8-hydroxy deoxy guanosine and DNA protein cross-links in discrete brain regions of young and aged rats. An age associated increase in ROS, superoxide anion production, LPO, protein oxidation, and DNA damage products in cortex, striatum, and hippocampus was observed which was reversed by GME. Contradictorily, a decline in the levels of glutathione, total thiol, and nonprotein and protein thiols was observed which was also reversed upon GME administration. These findings suggest that GME administration inhibits free radical-induced oxidative macromolecular damage in aged rats and thereby protects the brain from ROS.     

Chronic training increases blood oxidative damage but promotes health in elderly men

The objective of the present study was to investigate a large panel of oxidative stress biomarkers in long-term trained elderly men to analyse the effects of chronic training on an aged population. We collected blood samples from two groups of male volunteers older than 65 years who maintain a measure of functional independence: one group of sedentary subjects without a history of regular physical activity and the other of subjects who have sustained training, starting during middle age (mean training time = 49 ± 8 years). We studied morbidity and polypharmacy, as well as haematological parameters including red cell count, haemoglobin concentration, haematocrit, mean corpuscular volume, red cell distribution width and several oxidative biomarkers including protein carbonyl content and lipid peroxidation in plasma and erythrocytes, red blood cell H₂O₂-induced haemolysis test, plasma total antioxidant activity and the main antioxidant enzymes of erythrocytes: superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase. After adjusting for confounding factors, we observed an increase in all oxidative damage biomarkers in the plasma and erythrocytes of the long-term exercise group. However, we reported a decrease in the number of diseases per subject with statistical differences nearly significant (p = 0.061), reduced intake of medications per subject and lower levels of red cell distribution width in the chronic exercise group. These results indicate that chronic exercise from middle age to old age increases oxidative damage; however, chronic exercise appears to be an effective strategy to attenuate the age-related decline in the elderly.     

Systemic antioxidant defences during acute exacerbation of chronic obstructive pulmonary disease

OBJECTIVE AND BACKGROUND: Existence of an increased oxidative stress has been confirmed in patients with acute exacerbation of COPD. This study aims to examine the extent and time-course of antioxidant defence in patients with an acute exacerbation of COPD in comparison with stable patients. METHODS: Twelve patients with acute exacerbation were studied at admission, and then 24 h and 48 h following admission and at discharge. The antioxidants assessed were the endogenous antioxidants: glutathione peroxidase, superoxide dismutase, oxidized and reduced glutathione, albumin and exogenous antioxidants: alpha-tocopherol and retinol. Trolox equivalent antioxidant capacity as a marker of antioxidant status was also measured. RESULTS: There was an increase in glutathione peroxidase and superoxide dismutase 48 h after admission (P<0.05). Alpha-tocopherol was the lowest 24 h after admission and increased significantly at discharge (P<0.05). CONCLUSIONS: There is an increase in antioxidant defence during acute exacerbation of COPD reaching a maximum at 48 h after admission. This rise in the antioxidant defence is not sufficient to prevent depletion of non-enzymatic antioxidants such as alpha-tocopherol.     

Plasma oxidative stress parameters in men and women with early stage Alzheimer type dementia

It is well known that oxidative stress is one of the earliest events in Alzheimer's disease pathogenesis, indicating that may play a key role in this disease. In our study, we measured the levels of oxidative stress indicators (TBARS and protein carbonyls content) and the non-enzymatic (glutathione (GSH) and oxidized glutathione (GSSG)) and enzymatic (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) defense systems in the plasma of 46 patients diagnosed of ATD and 46 age-matched controls. We found decreased levels in total GSH in ATD patients, although healthy control women showed lower levels of total GSH than healthy control men. On the contrary, we found increased levels of TBARS and carbonyl groups content in ATD patients in both genders. The activity of the plasma antioxidant enzymes showed no changes for SOD activity in ATD patients, independently of the gender, although western blot analysis showed an increase in SOD-1 protein. CAT activity was also decreased in ATD patients, although this decrease is mainly due to the decrease found in men but not in women. However, western blot analysis did not show differences in CAT protein between controls and ATD patients. Finally, a decrease of GPx activity was found in ATD patients in both genders. However, as with CAT protein, western blot analysis did not show differences in GPx protein between controls and ATD patients. Our results suggest that there is a defect in the antioxidant defense system that is incapable of responding to increased free radical production, which may lead to oxidative damage and the development of the pathological alterations that characterize the neurodegenerative disorder of patients with ATD. Thus, oxidative damage could be one important aspect for the onset of ATD and oxidative stress markers could be useful to diagnose the illness in their earliest stages through both non-invasive, reliable and cost-affordable methods.     

Nitric Oxide and Antioxidant Defense in Patients with Gastric Cancer

In the present study, total nitrate and nitrite level (as end product of nitric oxide), superoxide dismutase activity, and glutathione peroxidase activity in leukocytes were determined in patients with gastric cancer, and the relationship between measured parameters and tumor grade were evaluated. Leukocyte nitrate and nitrite level was found to be increased and superoxide dismutase activity was found to be decreased in patients compared to controls. When the patient group was categorized, nitrate and nitrite level was found to be higher in patients with a high-grade tumor than in patients with a grade I tumor. We concluded that an increased level of leukocyte nitrate and nitrite is related to tumor grade in patients with gastric cancer; antioxidant activity is also impaired in these patients but it does not seem to be related to grade of tumor.     

Myocardial antioxidant status in chronic alcoholism

BACKGROUND: Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. The pathogenesis is multifactorial, with the antioxidant imbalance of cardiac muscle being a potential factor. The current study evaluates myocardial antioxidant status in ethanol consumers and its relation to cardiac damage. METHODS: The authors assessed superoxide dismutase, glutathione peroxidase, and glutathione reductase enzyme activities as well as the total antioxidant status capacity in myocardial samples obtained from organ donors with sudden death of traumatic or neurological origin. They studied 23 high-dose chronic alcohol consumers, 27 individuals with long-standing hypertension, and 11 healthy controls. Cardiomyopathy was defined according to standard functional and histological criteria. RESULTS: Patients with dilated cardiomyopathy, either of alcoholic or hypertensive origin, showed increased myocardial superoxide dismutase activities compared with patients without cardiomyopathy (p < 0.001, both) and controls (p < 0.05, both). Total antioxidant status capacity and the activity of glutathione peroxidase and glutathione reductase enzymes were similar in all groups. Superoxide dismutase activity was related to the presence of cardiac enlargement and the degree of cardiac histological damage. The amount and type of alcoholic beverages as well as the nutritional status of the patients were not related to myocardial antioxidant activity. CONCLUSIONS: The presence of dilated cardiomyopathy, of either alcoholic or hypertensive origin, is related to an increase in myocardial superoxide dismutase activity.