Effect of Low-Dose Aspirin on the Markers of Oxidative Stress

Summary. The present study estimates effects of low-dose enteric coated aspirin (ECA) on oxidative stress (OS) markers in a group of middle-aged men (mean age 51.2 ± 6.9 years) free of pre-existing ischemic heart disease.Methods. Serum products of lipid peroxidation, and measures of antioxidative status were detected in 25 healthy men in baseline and after two-week treatment period.Results. In respect to serum products of lipid peroxidation and markers of antioxidant status, no statistically significant differences between the pre- and after-treatment data were observed for any measures, with the exception of values of serum antioxidative capacity (39.0 ± 2.5 and 42 ± 4.6, respectively).Conclusions. Administration of ECA does not initiate the OS in blood and improves the general antioxidative potency of blood. This may imply towards certain antiatherogenic influence of low-dose ECA, exhibited even with a short-term treatment period. Regarding OS markers, a variety of individual responses observed in the selected subgroups should be investigated and possibly taken into account while treatment with ECA is initiated for primary prevention of cerebrovascular events.     

Clear differences in adiponectin level and glutathione redox status revealed in obese and normal-weight patients with psoriasis

Background Several studies have shown increased prevalence of obesity in patients with psoriasis. Objectives To characterize both inflammatory‐ and oxidative stress‐related differences between obese patients with psoriasis (OPP) and normal‐weight patients with psoriasis (NWPP). Methods The plasma concentrations of adiponectin and interleukin (IL)‐6 were analysed by quantitative sandwich enzyme immunoassay technique in 10 patients with a body mass index (BMI) < 25 and 12 patients with a BMI > 30. Total glutathione and oxidized glutathione levels were measured spectrophotometrically. Results Plasma concentration of adiponectin in NWPP was more than twice the level in healthy normal‐weight controls (P < 0·001), while such an elevation did not occur in OPP. OPP were characterized by a significantly increased IL‐6 level, which correlated negatively with the adiponectin level (r = ?0·85, P < 0·001). The glutathione redox status, which was also inversely correlated with the adiponectin level (r = ?0·63, P < 0·05), was associated with significantly increased oxidative stress in the OPP compared with the NWPP or controls. Conclusions Obesity in patients with psoriasis is associated with both decreased plasma levels of protective adiponectin compared with NWPP, and enhanced systemic inflammation and oxidative stress. These findings are in concordance with high prevalence of diseases related to lower adiponectin levels among psoriasis patients.     

Atherogenic inflammatory and oxidative stress markers in relation to overweight values in male former athletes

OBJECTIVE: To evaluate inflammation- and oxidative stress-related (OxS) background in former athletes in relation to overweight and abdominal obesity status. DESIGN: Cross-sectional data from ongoing follow-up study.Subjects:A total of 60 middle-aged former athletes (46.6+/-7.5 years; 181.1+/-7.2 cm; 88.1 +/- 12.9 kg) and 54 age-matched controls (48.1+/-7.3 years; 181.4 +/- 6.2 cm; 89.7 +/- 14.4 kg). MEASUREMENTS: Anthropometric characteristics, serum lipoproteins (CHOL, HDL-C, LDL-C, TG), oxidized LDL (oxLDL), diene conjugates (DC) and high-sensitive C-reactive protein (hsCRP). Information about the physical activity and other lifestyle variables were collected by the questionnaire. RESULTS: Ex-athletes were characterized by significantly higher physical activity characteristics and lower CHOL and oxLDL in comparison with controls. Correlation analysis among ex-athletes revealed negative associations between all measured overweight data (body mass index, fat percentage, waist to hip circumferences and waist circumference (WC)), and current physical activity. Current physical activity was significantly related to OxS and inflammatory characteristics (oxLDL, DC and hsCRP) among the ex-athletes, but not among the control group. The most expressed positive correlations were found between WC, hsCRP, triglycerides (TG), DC and oxLDL in both study groups. CONCLUSION: Our study results suggest that there exists an independent (adjusted for potential confounders) association between overweight, abdominal obesity, and atherogenic inflammatory and oxidative stress markers in ex-athletes as well as in age-matched controls. Major findings of our study show that WC is the best correlate of hsCRP, oxLDL, DC and TG levels.     

Allergic contact dermatitis is accompanied by severe abnormal changes in antioxidativity of blood.

We investigated whether the oxidative stress (OS) caused by skin inflammation could reflect in the blood, in a 21-year-old female student sensitized to nickel, colophony and abitole with often relapsing allergic contact dermatitis (ACD). As glutathione redox ratio was increased in the blood not only during the relapse but also in the beginning of remission phase, we prescribed natural medical preparations of d-alpha-tocopherol (in the first week 100 mg three times a day followed by 100 mg/day) and ascorbic acid (200 mg/day) for 25 days to her. After using antioxidants in the remission period, one of the principal OS markers-the glutathione redox ratio reached the normal physiological level. In this report, we showed that during acute extensive ACD OS is expressed in the blood and simultaneous supplementation of d-alpha-tocopherol and ascorbic acid might reduce systemic OS.     

Wfs1‐deficient animals have brain‐region‐specific changes of Na+, K+‐ATPase activity and mRNA expression of α1 and β1 subunits

Mutations in the WFS1 gene, which encodes the endoplasmic reticulum (ER) glycoprotein, cause Wolfram syndrome, a disease characterized by juvenile‐onset diabetes mellitus, optic atrophy, deafness, and different psychiatric abnormalities. Loss of neuronal cells and pancreatic β‐cells in Wolfram syndrome patients is probably related to the dysfunction of ER stress regulation, which leads to cell apoptosis. The present study shows that Wfs1‐deficient mice have brain‐region‐specific changes in Na⁺,K⁺‐ATPase activity and in the expression of the α₁ and β₁ subunits. We found a significant (1.6‐fold) increase of Na‐pump activity and β₁ subunit mRNA expression in mice lacking the Wfs1 gene in the temporal lobe compared with their wild‐type littermates. By contrast, exposure of mice to the elevated plus maze (EPM) model of anxiety decreased Na‐pump activity 1.3‐fold in the midbrain and dorsal striatum and 2.0‐fold in the ventral striatum of homozygous animals compared with the nonexposed group. Na‐pump α₁‐subunit mRNA was significantly decreased in the dorsal striatum and midbrain of Wfs1‐deficient homozygous animals compared with wild‐type littermates. In the temporal lobe, an increase in the activity of the Na‐pump is probably related to increased anxiety established in Wfs1‐deficient mice, whereas the blunted dopamine function in the forebrain of Wfs1‐deficient mice may be associated with a decrease of Na‐pump activity in the dorsal and ventral striatum and in the midbrain after exposure to the EPM. © 2014 Wiley Periodicals, Inc.     

Very low levels of cholecystokinin octapeptide activate Na-pump in the cerebral cortex of CCK2 receptor-deficient mice

This study provides the first evidence that CCK-8 (0.01 pM to 0.1 mM) stimulates Na,K-ATPase in the cortical membranes of wild-type and CCK(2) receptor-deficient mice. In each genotype, the maximal stimulation was about 40%. Homozygous mice revealed substantially lower EC50 (4 pM) than heterozygous (37 pM) or wild-type animals (682 pM). In homozygous CCK2 receptor-deficient mice, the expression of CCK1 receptor gene was 5-fold higher than in wild-type animals. CCK1 receptor antagonist devazepide counteracted effect of CCK-8 in all three genotypes, whereas CCK2 receptor antagonist L-365, 260 showed significant antagonism in wild-type and heterozygous mice. The cooperativity of Na,K-ATPase for Na+, but not for K+, was lost in homozygous mice. Altogether, very low concentrations of CCK-8 via CCK1 and CCK2 receptors stimulate Na,K-ATPase in the cerebral cortex. CCK2 receptor-deficiency leads to the altered functionality of Na,K-ATPase that might be compensated by CCK1 receptor mediated influence of CCK (and its agonists) on the enzyme.     

Pre-treatment with hyperoxia before coronary artery bypass grafting - effects on myocardial injury and inflammatory response

BACKGROUND: In experimental studies, exposure to hyperoxia for a limited time before ischaemia induces a low-grade systemic oxidative stress and evokes an (ischaemic) preconditioning-like effect of the myocardium. We hypothesised that hyperoxia before cardioplegia could protect the myocardium against necrosis and stunning caused by ischaemia-reperfusion. METHODS: Forty patients undergoing coronary artery bypass grafting were randomly exposed to an oxygen fraction of 0.4 or > 0.96 in inspired air on an average of 120 min before cardioplegia. Blood for troponin I, creatine kinase-MB, lactate, glutathione and interleukin-6 was sampled from arterial and coronary sinus cannulae during 20 min of reperfusion. Additional arterial samples were drawn 60 min after declamping and in the first post-operative morning. The cardiac index and right and left ventricular stroke work indices were measured before sternotomy and up to 12 h post-operatively. RESULTS: Troponin I, creatine kinase-MB and lactate did not differ between the groups. Hyperoxic pre-treatment had no impact on the post-operative haemodynamic indices measured with the thermodilution pulmonary artery catheter. More oxidised glutathione was released in the hyperoxia group in the first minute of reperfusion (P = 0.015). Hyperoxic pre-treatment abolished the myocardial release of interleukin-6 during 20 min of reperfusion (P = 0.021 vs. controls). In the first post-operative morning, interleukin-6 was higher in the hyperoxia group [127.0 (86.0-140.0) vs. 85.2 pg/ml (66.6-94.5 pg/ml); P = 0.016]. Conclusions: Exposure to >96% oxygen before cardioplegia did not attenuate ischaemia-reperfusion injury of the heart in patients undergoing coronary artery bypass grafting. The only potentially beneficial effect observed was the decreased transmyocardial release of interleukin-6.     

Effect of antihypertensive treatment with candesartan or amlodipine on glutathione and its redox status, homocysteine and vitamin concentrations in patients with essential hypertension

OBJECTIVE: To compare the effect of candesartan or amlodipine on concentrations of cellular markers of oxidative stress, plasma homocysteine and vitamins in hypertensive patients. METHODS: Forty-nine middle-aged patients with untreated stage I-II essential hypertension were recruited in a randomized double-blind double-dummy study to receive a daily dose either of 8 mg candesartan (n = 25) or 5 mg amlodipine (n = 24) for 16 weeks. Blood pressure, reduced glutathione (GSH) and oxidized glutathione (GSSG), glutathione redox ratio (GSSG : GSH) in red blood cells, plasma homocysteine, vitamin B12 and folic acid status were measured at baseline, at week 2 and at week 16. The same parameters were measured in 32 healthy age- and sex-matched controls. An increase in homocysteine of at least 2 micromol/l was considered significant. RESULTS: Hypertensive patients had significantly greater oxidative stress and homocysteine concentrations than controls. In addition to a significant decrease in blood pressure, in both treatment groups GSSG decreased (P < 0.03), GSSG : GSH had a tendency to decrease (P = 0.054), but homocysteine did not change. An increase in homocysteine concentration of at least 2 micromol/l was found in 12 patients (five in the candesartan group, seven in the amlodipine group), with a significant decrease in folic acid concentration and no changes in cellular oxidative stress. In patients with no increase in homocysteine concentration, both GSSG (P < 0.02) and GSSG : GSH (P = 0.051) decreased. GSH and vitamin B12 did not change in any of the groups studied. CONCLUSION: Untreated hypertension is associated with disturbed glutathione redox status and increased plasma homocysteine concentrations. Both candesartan and amlodipine had favourable effects on cellular oxidative stress, but the oxidative stress status did not decrease in patients with adverse changes in homocysteine.     

Early postoperative function of the heart after coronary artery bypass grafting is not predicted by myocardial necrosis and glutathione-associated oxidative stress

BACKGROUND: To investigate whether cardioplegia-related myocardial necrosis, lactate and glutathione release are predictive for early postoperative cardiac function after coronary artery bypass grafting (CABG). METHODS: Twelve patients with stabile angina scheduled for elective CABG were included. Myocardial release of troponin I (Tn I), creatine kinase MB isoenzyme mass (CK-MB), oxidized glutathione (GSSG) and lactate in blood were measured before cardioplegia, and up to 20 min thereafter. Cardiac function was assessed for 12 postoperative hours. RESULTS: Release of Tn I and CK-MB peaked at 20 min (-14.5+/-24.1 ng/ml and -23.9+/-30.6 ng/ml, respectively) and lactate at 1 min of reperfusion (-1.5+/-0.6 mmol/l). Significant GSSG release occurred at 5 min, with concomitant increase of glutathione redox ratio. The changes were not correlated to ischemic time. Cardiac index was increased after CPB and remained higher than preoperative value until the first postoperative morning. No correlations between postcardioplegic heart function and markers of tissue injury were found. CONCLUSIONS: The extent of myocardial reversible and irreversible injury does not predict early postoperative contractile function of the heart.