Systemic Oxidative Stress Markers Research Articles

Effect of Roux-en-Y Bariatric Bypass Surgery on Subclinical Atherosclerosis and Oxidative Stress Markers in Leukocytes of Obese Patients: A One-Year Follow-Up Study.

Little is known about the mechanisms underlying the cardioprotective effect of Roux en-Y gastric bypass (RYGB) surgery. Therefore, the aim of the present study was to investigate whether weight loss associated with RYGB improves the oxidative status of leukocytes and ameliorates subclinical atherosclerotic markers. This is an interventional study of 57 obese subjects who underwent RYGB surgery. We determined biochemical parameters and qualitative analysis of cholesterol, leukocyte and systemic oxidative stress markers —superoxide production, glutathione peroxidase 1 (GPX1), superoxide dismutase (SOD) activity and protein carbonylation—, soluble cellular adhesion molecules —sICAM-1 and sP-selectin—, myeloperoxidase (MPO) and leukocyte-endothelium cell interactions—rolling flux, velocity and adhesion. RYGB induced an improvement in metabolic parameters, including hsCRP and leukocyte count (p < 0.001, for both). This was associated with an amelioration in oxidative stress, since superoxide production and protein carbonylation were reduced (p < 0.05 and p < 0.01, respectively) and antioxidant systems were enhanced (GPX1; p < 0.05 and SOD; p < 0.01). In addition, a significant reduction of the following parameters was observed one year after RYGB: MPO and sICAM (p < 0.05, for both), sPselectin and pattern B of LDL particles (p < 0.001, for both), and rolling flux and adhesion of leukocytes (p < 0.05 and p < 0.01, respectively). Our results suggest that patients undergoing RYGB benefit from an amelioration of the prooxidant status of leukocytes, metabolic outcomes, and subclinical markers of atherosclerosis.

The effect of conservative oxygen therapy on systemic biomarkers of oxidative stress in critically ill patients

BackgroundSupplemental oxygen is delivered to critically ill patients who require mechanical ventilation. Oxidative stress is a potential complication of oxygen therapy, resulting in damage to essential biomolecules such as proteins, lipids, and nucleic acids. Whether plasma levels of oxidative stress biomarkers vary based on how liberally oxygen therapy is applied during mechanical ventilation is unknown. MethodsWe carried out an oxidative stress substudy nested within a large multi-centre randomized controlled trial in which critically ill adults were randomized to receive either conservative oxygen therapy or standard oxygen therapy. Blood samples were collected at enrolment, and daily thereafter for up to three days. The antioxidant ascorbate (vitamin C) was assessed using HPLC with electrochemical detection and protein oxidation using a sensitive protein carbonyl ELISA. We also assessed whether critically ill patients with different disease states exhibited varying levels of oxidative stress biomarkers. ResultsA total of 125 patients were included. Mean ascorbate concentrations decreased over time (from 25 ± 9 μmol/L to 14 ± 2 μmol/L, p < 0.001), however, there was no significant difference between the conservative oxygen group and standard care (p = 0.2), despite a significantly lower partial pressure of oxygen (PaO2) in the conservative oxygen group (p = 0.03). Protein carbonyl concentrations increased over time (from 208 ± 30 μmol/L to 249 ± 29 μmol/L; p = 0.016), however, there was no significant difference between the conservative and standard oxygen groups (p = 0.3). Patients with sepsis had significantly higher protein carbonyl concentrations than the other critically ill patients (293 ± 92 μmol/L vs 184 ± 24 μmol/L, p = 0.03). Within the septic subgroup, there were no significant differences in protein carbonyl concentrations between the two interventions (p = 0.4). ConclusionsConservative oxygen therapy does not alter systemic markers of oxidative stress in critically ill ventilated patients compared with standard oxygen therapy. Patients with sepsis exhibited elevated protein carbonyls compared with the other critically ill patients implying increased oxidative stress in this patient subgroup.

Poor Adherence to Mediterranean Diet and Serum Lipopolysaccharide Are Associated with Oxidative Stress in Patients with Non-Alcoholic Fatty Liver Disease

Oxidative stress plays a pivotal role in non-alcoholic fatty liver disease (NAFLD). Factors inducing oxidative stress in NAFLD may be several; however, a relationship with the adherence to Mediterranean Diet (Med-diet) and with serum lipopolysaccharide (LPS) has been poorly investigated in this setting. The aim was to investigate factors associated with impaired oxidative stress in NAFLD, focusing on the potential role of LPS and Med-diet. We enrolled 238 consecutive outpatients from the PLINIO study, in whom we measured the soluble Nox2-derived peptide (sNox2-dp), a marker of systemic oxidative stress, and serum LPS. Adherence to Med-diet was investigated by a nine-item validated dietary questionnaire. Serum sNox2-dp and LPS were higher in patients with NAFLD compared to those without (25.0 vs. 9.0 pg/mL, p < 0.001 and 62.0 vs. 44.9 pg/mL, p < 0.001, respectively). In patients with NAFLD, the highest sNox2-dp tertile was associated with the top serum LPS tertile (Odds Ratio (OR): 4.71; p < 0.001), APRI > 0.7 (OR: 6.96; p = 0.005) and Med-diet-score > 6 (OR: 0.14; p = 0.026). Analyzing individual foods, the daily consumption of wine (OR: 0.29, p = 0.046) and the adequate weekly consumption of fish (OR: 0.32, p = 0.030) inversely correlated with the top sNox2-dp tertile. In conclusion, patients with NAFLD showed impaired oxidative stress. Levels of sNox2 correlated with serum LPS and with low adherence to Med-Diet.

Features of clinical and laboratory indicators in alcoholic liver disease in combination with arterial hypertension depending on T786C polymorphism of the eNOS gene

The goal of the work. Assess the relationship between eNOS gene genotypes (T786C) and some clinical and laboratory parameters in patients with alcoholic liver disease (ALD) in combination with arterial hypertension (AH).Material and methods. 97 patients diagnosed with AHP were examined: 62 patients with ALD with AH (group A) and 35 patients with ALD (group B). Serum content of C-reactive protein, tumor necrosis factor-α (TNFα), transforming growth factor-β1 (TGFβ1), interleukin-10 (IL-10), 8-isoprostane, D-dimer was determined by enzyme-linked immunosorbent assay. The functional state of the endothelium was assessed by the content in the blood of stable metabolites of nitrogen monoxide (nitrites / nitrates), endothelin-1 (ET-1), intercellular adhesion molecules-1 (ICAM-1). Total blood coagulation potential (plasma recalcification time), prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), plasma fibrinogen levels, antithrombin III (ATIII) activity, factor XIII (F XIII) activity was determined by traditional methods. Spontaneous platelet aggregation was also studied. To determine the eNOS mutation (T786C), rs2070744 used a protocol with oligonucleotide primers using the method of allele-specific PCR.Results. When studying the frequency of genotypes by the polymorphic variant of the eNOS gene (T786C), it was found that the frequency of TT genotype among patients with ALD with hypertension was 46.8%, CT - 57.1% and SS - 17.2%. Among patients with ALD, the following distribution of genotypes was found: TT - 25.7%, ST - 57.1% and SS - 17.2%. We found a significant difference between the group of patients with ALD with AH and the isolated group of ALD by TT genotype. It was found that the level of ET-1 and the intercellular adhesion molecule (ICAM-1) were significantly higher in patients with ALD with AH by TT genotype compared with the isolated course of ALD. However, the level of total nitric oxide in the combined course of ALD with hypertension was lower than in patients with ALD without hypertension in the presence of this genotype. At the same time, in the combined course of ALD and hypertension, the level of systemic inflammation and oxidative stress is associated with the TT genotype by a polymorphic variant of the eNOS gene (T786C). When studying the state of hemostasis in the combined course of ALD and hypertension, it was found that APTT for the TT genotype was 17.7% higher than in group B. This indicator also had a difference in the middle group between the TT and CT genotypes (by 13.1%) and TT and CC (by 28.3%). The level of D-dimer between groups A and B also had a significant difference in the TT genotype (higher by 14.7% for the combination of ALD and AH). Spontaneous platelet aggregation was significantly higher by 7.7% in patients with ALD with hypertension by TT genotype. In the latter group of patients, factor XIII was significantly lower by 12.6% compared with the group of patients with ALD. Indicators such as plasma recalcification time, prothrombin index and time, thrombin time did not differ significantly between groups of patients.Conclusion. The development of hypertension in patients with ALD is associated with the presence of a homozygous TT genotype for a polymorphic variant of the eNOS gene (T786C). It was found that in patients with ALD with hypertension by TT genotype higher levels of ET-1 and intercellular adhesion molecules ICAM-1 are observed at a lower level of total nitric oxide compared with patients with ALD. The most probable differences in systemic inflammation (IL-10, CRP, TGFβ1) and oxidative stress marker (8-isoprostane) are characteristic of the TT genotype for the polymorphic variant of the eNOS gene (T786C) in patients with ACP with hypertension compared with the isolated course of ALD. Hemostasis parameters such as APTT, antithrombin III, D-dimer, spontaneous platelet aggregation and factor XIII were associated with the TT genotype in patients with ALD with hypertension by the polymorphic variant of the eNOS gene (T786C).

Simulated vehicle exhaust exposure (SVEE) in rats impairs renal mitochondrial function

ABSTRACT Purpose Vehicle exhaust emissions primarily comprise of nitrogen, oxygen, water, CO2, NO2, CO, hydrocarbons and particulate matter. While adverse effects of hydrocarbon and particulate matter on cardiovascular functions are known, the effect of pro-oxidants CO2, NO2 and CO are not clear. Methods Here, using an animal model of a simulated mixture of pro-oxidants (0.04% CO2, 0.9 ppm NO2 and 3 ppm CO with air as a base), we examined the effect of simulated vehicle exhaust exposure (SVEE) on various cardiovascular parameters. Male Sprague-Dawley rats were exposed to SVEE or ambient air (Control: CON) for 30 min/day for 2 weeks. Thereafter, systolic and diastolic blood pressure, heart rate and glomerular filtration rate were measured. Later, rats were sacrificed, blood plasma and kidneys were collected. Results The systolic and diastolic blood pressure, heart rate and glomerular filtration rate remained unchanged. Plasma corticosterone increased in SVEE rats when compared to CON group. Plasma 8-isoprostane, a systemic marker of oxidative stress, increased while total antioxidant capacity decreased in SVEE but not in CON. Kidney cortical tissue homogenates exhibited increase in superoxide, hydrogen peroxide and protein carbonylation in SVEE but not CON, all indicative of heightened oxidative stress. Renal cortical mitochondrial SOD activity was significantly reduced in SVEE than CON. Conclusion Significant decline in mitochondrial respiration and oxygen consumption was observed, in addition to low ATP, reduced ATP synthase and cytochrome C oxidase levels, as well as accelerated mitochondrial fission, and reduced fusion processes, were observed in SVEE than CON rats, all indicative of renal mitochondrial impairment.

Systemic Oxidative Stress Markers in Cirrhotic Patients with Hepatic Encephalopathy: Possible Connections with Systemic Ammoniemia.

Background and objectives: Oxidative stress shows evidence of dysregulation in cirrhotic patients with hepatic encephalopathy (HE), although there are still controversies regarding the connections between oxidative stress and ammonia in these patients. The aim of this study was to evaluate the oxidative stress implication in overt HE pathogenesis of cirrhotic patients. Materials and Methods: We performed a prospective case-control study, which included 40 patients divided into two groups: group A consisted of 20 cirrhotic patients with HE and increased systemic ammoniemia, and group B consisted of 20 cirrhotic patients with HE and normal systemic ammoniemia. The control group consisted of 21 healthy subjects matched by age and sex. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) levels (lipid peroxidation marker), and ammoniemia were evaluated. Results: We found a significant decrease in SOD and GPx activity and also a significant increase of MDA levels in cirrhotic patients with HE as compared to the healthy age-matched control group (1.35 ± 0.08 vs. 0.90 ± 0.08 U/mL, p = 0.002; 0.093 ± 0.06 vs. 0.006 ± 0.008 U/mL, p = 0.001; and 35.94 ± 1.37 vs. 68.90 ± 5.68 nmols/mL, p = 0.0001, respectively). Additionally, we found significant correlations between the main oxidative stress markers and the levels of systemic ammonia (r = 0.452, p = 0.005). Patients from group A had a significant increase of MDA as compared with those from group B (76.93 ± 5.48 vs. 50.06 ± 5.60 nmols/mL, p = 0.019). Also, there was a compensatory increase in the activity of both antioxidant enzymes (SOD and GPx) in patients with increased systemic ammoniemia (group A), as compared to HE patients from group B. Conclusions: Our results demonstrated a significant decrease in antioxidants enzymes activities (SOD and GPx), as well as a significant increase in MDA concentrations, adding new data regarding the influence of oxidative stress in HE pathogenesis in cirrhotic patients.

Inflammation and the Cardiovascular Responses to Exercise in Patients with Peripheral Artery Disease

BackgroundPatients with peripheral artery disease (PAD) demonstrate an exaggerated exercise pressor response (EPR). Heightened inflammation critically contributes to this exaggerated EPR in animal models of PAD, however, this relationship remains largely unexplored in humans. Therefore, we tested the hypotheses that the blood pressure response to exercise would be exaggerated in patients with PAD compared to controls; and that markers of inflammation would be positively related to this response.MethodsEight patients with PAD (ABI: 0.67±0.11) and eight healthy controls (HC; ABI: 1.16±0.07) matched for age, sex, physical activity, and physical characteristics completed plantar flexion exercise at both absolute (2.7 W) and relative (40% max; PAD: 2.1±0.2 vs HC: 4.3±0.4 W, p&lt;0.001) intensities. Popliteal artery blood flow (Flow) was measured via Doppler ultrasound and systemic mean arterial pressure (MAP) via Finapres. Resting systemic and intramuscular markers of inflammation and oxidative stress were quantified from plasma and muscle biopsies.ResultsThe exercise‐induced ΔMAP was greater for PAD at both the absolute (PAD: 20±3 vs HC: 9±2 mmHg, p&lt;0.01) and relative (PAD: 23±5 vs HC: 11±2 mmHg, p=0.02) exercise intensities. The ΔFlow was lower for PAD compared to HC during both absolute (PAD: 251±53 vs HC: 545±66 ml/min, p&lt;0.01) and relative intensities (PAD: 242±61 vs HC: 595±89 ml/min, p&lt;0.01). Inflammatory markers including plasma tumor necrosis factor alpha (TNFα: ↑134%), interleukin‐6 (IL6: ↑92%), and intramuscular IL6 (↑77%) were elevated in PAD compared to HC (p&lt;0.05). Additionally, markers of oxidative stress including intramuscular protein carbonyls (PC: ↑57%) and 4‐hydroxynonenal (HNE: ↑80%) were elevated in PAD (p&lt;0.05). TNFα, plasma IL6, and PC were positively correlated with ΔMAP (r: 0.57–0.82, all p&lt;0.05) while plasma and intramuscular IL6, PC, and HNE were negatively correlated with ΔFlow (r: 0.64–0.78, all p&lt;0.05).ConclusionsThe present findings indicate an association between markers of inflammation with the cardiovascular responses to exercise in humans with PAD. Specifically, heightened inflammation and oxidative stress appear to contribute to the exaggeration the exercise pressor reflex and attenuated blood flow response during lower limb exercise in PAD. Therapeutically, targeting systemic and local inflammation may be a viable option to improve the blood pressure and blood flow responses to exercise in patients with PAD.

Oxidative stress and Nrf2 expression in peripheral blood mononuclear cells derived from COPD patients: an observational longitudinal study

BackgroundA persistent low inflammatory-oxidative status and the inadequacy of the antioxidant nuclear factor-E2-related factor 2 (Nrf2) have been implicated in chronic obstructive pulmonary disease (COPD) progression. Therefore this study was aimed to assess the association between lung function decline and oxidative-inflammatory markers and Nrf2 signaling pathway expression in peripheral blood mononuclear cells (PBMCs) over time.Methods33 mild-moderate COPD outpatients (mean age 66.9 ± 6.9 years) were age-sex matched with 37 no-COPD subjects. A clinical evaluation, blood sampling tests and a spirometry were performed at baseline and after a mean follow-up of 49.7 ± 6.9 months.ResultsIn COPD, compared to no-COPD, we found a faster lung function decline at follow-up. Although similar prevalence of smoking, hypertension, diabetes and dyslipidemia, systemic markers of inflammation (hs-CRP and white blood cells, WBCs) and oxidative stress (8-isoprostane) were significantly increased in COPD at follow-up, while the antioxidant glutathione (GSH) was significantly reduced. Moreover the expression of Nrf2 and of Nrf2-related genes heme oxygenase (HO)-1 and glutamate-cysteine ligase catalytic (GCLC) subunit in PBMCS were significantly down-regulated in COPD at follow-up, whereas no changes were observed in no-COPD. The percent variation (Δ) of FEV1 detected after the follow-up in COPD patients was directly correlated with ΔNrf2 (r = 0.826 p < 0.001), ΔHO-1 (r = 0.820, p < 0.001) and ΔGCLC (r = 0.840, p < 0.001). Moreover ΔFEV1 was also directly correlated with ΔGSH (r = 0.595, p < 0.01) and inversely correlated with Δ8-iso (r = − 0.587, p < 0.01) and with baseline smoking history (r = − 0.39, p < 0.03). No correlation was found between ΔFEV1, ΔCRP and ΔWBCs. By means of hierarchical stepwise multiple linear regression, taking into account other baseline key factors related to FEV1, ΔNrf2, ΔHO-1and ΔGCLC were found to be significant predictors of ΔFEV1, explaining 89.5% of its variance.ConclusionsAlthough our results must be confirmed in larger trial they suggest that the down-regulation of Nrf2/ARE gene expression in PBMCs may be one of the determinants of FEV1 decline and of COPD progression. Therefore the future possibility to counteract Nrf2 decline in COPD patients may help in reducing the negative effects of the oxidative stress-induced progression of the disease.

Changes in systemic and subcutaneous adipose tissue inflammation and oxidative stress in response to exercise training in obese black African women.

Inflammation and oxidative stress are interrelated during obesity and contribute to the development of insulin resistance; and exercise training represents a key component in the management of these conditions. Black African women, despite high gluteal subcutaneous adipose tissue (SAT) and less visceral fat, are less insulin sensitive than their white counterparts. Exercise training improved systemic oxidative stress in obese black women, which was related to gynoid fat reduction and not insulin sensitivity. Inflammatory markers changed depot-specifically in response to exercise training, increasing in gluteal SAT without changing in abdominal SAT. The increase of inflammatory state in gluteal SAT after exercise training is suggested to result from tissue remodelling consecutive to the reduction of gynoid fat but does not contribute to the improvement of whole-body insulin sensitivity in obese black South African women. Inflammation and oxidative stress are interrelated during obesity and contribute to the development of insulin resistance. Exercise training represents a key component in the management of obesity. We evaluated the effects of 12weeks' combined resistance and aerobic exercise training on systemic and abdominal vs. gluteal subcutaneous adipose tissue (SAT) inflammatory and oxidative status in obese black South African women. Before and after the intervention, body composition (dual energy X-ray absorptiometry), cardio-respiratory fitness ( ), serum and SAT inflammatory and oxidative stress markers were measured from 15 (control group) and 20 (exercise group) women and insulin sensitivity (SI ; frequently sampled intravenous glucose tolerance test) was estimated. Following the intervention, (9.8%), body fat composition (1-3%) and SI (9%) improved, serum thiobarbituric acid reactive substances (TBARS) decreased (6.5%), and catalase activity increased (23%) in the exercise compared to the control group (P<0.05), without changes in circulating inflammatory markers. The mRNA content of interleukin-10, tumour necrosis factor α, nuclear factor κB and macrophage migration inhibitory factor increased in the gluteal SAT exercise compared to the control group P<0.05), with no changes in abdominal SAT. These changes of inflammatory profile in gluteal SAT, in addition to the reduction of circulating TBARS, correlated with the reduction of gynoid fat, but not with the improvement of SI . The changes in systemic oxidative stress markers and gluteal SAT inflammatory genes correlated with the reduction in gynoid fat but were not directly associated with the exercise-induced improvements in SI .

Markers of HPA-axis activity and nucleic acid damage from oxidation after electroconvulsive stimulations in rats.

Oxidative stress has been suggested to increase after electroconvulsive therapy (ECT), a treatment which continues to be the most effective for severe depression. Oxidative stress could potentially be mechanistically involved in both the therapeutic effects and side effects of ECT. We measured sensitive markers of systemic and central nervous system (CNS) oxidative stress on DNA and RNA (urinary 8-oxodG/8-oxoGuo, cerebrospinal fluid 8-oxoGuo, and brain oxoguanine glycosylase mRNA expression) in male rats subjected to electroconvulsive stimulations (ECS), an animal model of ECT. Due to the previous observations that link hypothalamic-pituitary-adrenal (HPA)-axis activity and age to DNA/RNA damage from oxidation, groups of young and middle-aged male animals were included, and markers of HPA-axis activity were measured. ECS induced weight loss, increased corticosterone (only in middle-aged animals), and decreased cerebral glucocorticoid receptor mRNA expression, while largely leaving the markers of systemic and CNS DNA/RNA damage from oxidation unaltered. These results suggest that ECS is not associated with any lasting effects on oxidative stress on nucleic acids neither in young nor middle-aged rats.

Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients

Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.

Plasma mitochondrial DNA is elevated in obese type 2 diabetes mellitus patients and correlates positively with insulin resistance.

Cells damaged by mechanical or infectious injury release proinflammatory mitochondrial DNA (mtDNA) fragments into the circulation. We evaluated the relation between plasma levels of mtDNA fragments in obese type 2 diabetes mellitus (T2DM) patients and measures of chronic inflammation and insulin resistance. In 10 obese T2DM patients and 12 healthy control (HC) subjects, we measured levels of plasma cell-free mtDNA with quantitative real-time polymerase chain reaction, and mtDNA damage in skeletal muscle with quantitative alkaline Southern blot. Also, markers of systemic inflammation and oxidative stress in skeletal muscle were measured. Plasma levels of mtDNA fragments, mtDNA damage in skeletal muscle and plasma tumor necrosis factor α levels were greater in obese T2DM patients than HC subjects. Also, the abundance of plasma mtDNA fragments in obese T2DM patients levels positively correlated with insulin resistance. To the best of our knowledge, this is the first published evidence that elevated level of plasma mtDNA fragments is associated with mtDNA damage and oxidative stress in skeletal muscle and correlates with insulin resistance in obese T2DM patients. Plasma mtDNA may be a useful biomarker for predicting and monitoring insulin resistance in obese patients.

Markers of systemic inflammatory response, oxidative stress, and endothelial dysfunction in patients with arterial hypertension combined with rheumatoid arthritis with diastolic dysfunction

Introduction. In patients with rheumatoid arthritis (RA) in combination with arterial hypertension (AH) the early development of cardiovascular complications is caused by chronic systemic inflammation, a high level of pro-inflammatory cytokines and lipid peroxidation products (LPO).Aim of the research. For the purpose of early diagnosis of complications, study of the diastolic function of the left ventricle (LV) in patients with AH in combination with RA and determine the predictor value of LPO, endothelial function (EF), markers of a systemic inflammatory response regarding impaired LV diastolic function, and detection of exudate in the pericardial cavity.Materials and methods. We examined 96 patients with stage II of AH in combination with RA, 45 patients with stage II arterial hypertension and 31 healthy subjects. Patients underwent echocardioscopy and we determined the levels of isolated double bonds, Schiff’s bases, diene conjugates, diene ketones, malonic aldehyde, vitamins A, E, catalase, asymmetric dimethylargenini (ADMA), interleukin-1 beta (IL 1-B), interleukin-10 ( IL 10), a highly sensitive C-reactive protein (hs-CRP) and the level of final serum nitric oxide metabolites.Conclusins. The highest predictor value with respect to impaired LV diastolic function in AH patients in combination with RA was found in the indicator IL 1-B, AUC 0.882, sensitivity 72.15%, specificity 100% with an optimal distribution point &gt;9.67 pg / ml, and relatively for detecting fluid in the pericardial cavity at an ADMA AUC of 0.913 with an optimal distribution point &gt;0.841 μmol / L, sensitivity 94.12%, specificity 85.53%

Ozone effects on blood biomarkers of systemic inflammation, oxidative stress, endothelial function, and thrombosis: The Multicenter Ozone Study in oldEr Subjects (MOSES).

The evidence that exposure to ozone air pollution causes acute cardiovascular effects is mixed. We postulated that exposure to ambient levels of ozone would increase blood markers of systemic inflammation, prothrombotic state, oxidative stress, and vascular dysfunction in healthy older subjects, and that absence of the glutathione S-transferase Mu 1 (GSTM1) gene would confer increased susceptibility. This double-blind, randomized, crossover study of 87 healthy volunteers 55–70 years of age was conducted at three sites using a common protocol. Subjects were exposed for 3 h in random order to 0 parts per billion (ppb) (filtered air), 70 ppb, and 120 ppb ozone, alternating 15 min of moderate exercise and rest. Blood was obtained the day before, approximately 4 h after, and approximately 22 h after each exposure. Linear mixed effect and logistic regression models evaluated the impact of exposure to ozone on pre-specified primary and secondary outcomes. The definition of statistical significance was p<0.01. There were no effects of ozone on the three primary markers of systemic inflammation and a prothrombotic state: C-reactive protein, monocyte-platelet conjugates, and microparticle-associated tissue factor activity. However, among the secondary endpoints, endothelin-1, a potent vasoconstrictor, increased from pre- to post-exposure with ozone concentration (120 vs 0 ppb: 0.07 pg/mL, 95% confidence interval [CI] 0.01, 0.14; 70 vs 0 ppb: -0.03 pg/mL, CI -0.09, 0.04; p = 0.008). Nitrotyrosine, a marker of oxidative and nitrosative stress, decreased with increasing ozone concentrations, with marginal significance (120 vs 0 ppb: -41.5, CI -70.1, -12.8; 70 vs 0 ppb: -14.2, CI -42.7, 14.2; p = 0.017). GSTM1 status did not modify the effect of ozone exposure on any of the outcomes. These findings from healthy older adults fail to identify any mechanistic basis for the epidemiologically described cardiovascular effects of exposure to ozone. The findings, however, may not be applicable to adults with cardiovascular disease.

Different routes of insulin administration do not influence serum free thiols in type 1 diabetes mellitus.

AimsIntraperitoneal (IP) insulin administration is a last‐resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As the IP route of insulin administration mimics the physiology more closely than the subcutaneous (SC) route, we hypothesized that IP insulin would result in less oxidative stress (expressed as systemic level of free sulphydryl (R‐SH) content) compared to SC insulin in subjects with T1DM.Materials and methodsProspective, observational case‐control study. Serum thiol measurements were performed at baseline and at 26 weeks in age‐ and gender‐matched patients with T1DM. Serum‐free thiols, compounds with a R‐SH group that are readily oxidized by reactive oxygen species, are considered to be a marker of systemic redox status.ResultsA total of 176 patients, 39 of which used IP and 141 SC insulin therapy were analysed. Mean baseline R‐SH concentration was 248 (31) μmol/L. In multivariable analysis, the route of insulin therapy had no impact on baseline R‐SH levels. The estimated geometric mean concentrations of R‐SH did not differ significantly between both groups: 264 (95% CI 257, 270) for the IP group and 258 (95% CI 254, 261) for the SC group with a difference of 6 (95% CI −2, 14) μmol/L.ConclusionsBased on R‐SH as a marker of systemic oxidative stress, these findings demonstrate that the route of insulin administration, IP or SC, does not influence systemic redox status in patients with T1DM.

PROLONGED EXPOSURE TO DIFFERENT TYPES OF ENERGY RESTRICTED CALCIUM DIET MODULATES THE INFLAMMATORY AND OXIDATIVE STRESS RESPONSE IN HEALTHY MALE RATS

Objective: Emerging evidence established the role of dietary calcium in the modulation of obesity. Obesity is known to induce inflammatory and oxidative stress in adipocytes resulting in several metabolic complications. In the present study, we evaluated the role of low and high calcium diet on systemic inflammatory response and oxidative stress markers in both plasma and hepatic tissues in male rats.&#x0D; Methods: A total of 30 male rats were divided into three groups and fed with control, low calcium (0.25%), and high calcium (1.0%) diet for 3 months. All the diets were isocaloric in nature. At the end of the treatment, all rats were sacrificed, followed by collection of blood and hepatic tissue for inflammatory, oxidative, antioxidant, and histological study.&#x0D; Results: Rats fed with a low calcium diet showed a significant increase in the body weight gain, liver mass, plasma inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. Low calcium diet significantly increased the lipid peroxidation and protein carbonylation and decreased the superoxide dismutase and glutathione peroxidase activities in both plasma and liver. High calcium diet, on the other hand, showed the reversed effect.&#x0D; Conclusion: Low calcium in the diet, along with obesity, increases the systemic inflammatory response, which in turn increases oxidative stress both in blood and hepatic tissues. This might be associated with obesity-induced hepatic disorder. High calcium in diet attenuates this effect.

1166-P: Bromocriptine-QR (BQR) Therapy Reduces Elevated Sympathetic Nervous System Activity (SNSA) and Oxidative Stress (OS) in Type 2 Diabetes (T2D) Subjects whose Dysglycemia Is Poorly Controlled on GLP-1 Receptor Agonist (GLP-1RA)

Elevated SNSA induces dysglycemia by enhancing adipose lipolysis and stimulating hepatic glucose production. It also promotes cardiovascular disease (CVD) by multiple mechanisms including augmenting systemic and vascular reactive oxygen and nitrogen species (ROS, RNS) generation. Elevated plasma prolactin (subclinical hyperprolactinemia) has also been associated with systemic inflammation, which can potentiate dysglycemia and CVD. BQR, the only dopamine agonist approved for treatment of T2D, improves postprandial dysglycemia and reduces CVD events. To evaluate mechanisms for the glucose lowering and CVD protective effects of BQR, we evaluated BQR’s effect on plasma markers of SNSA and ROS/RNS and plasma prolactin and leptin from a mechanistic study in which BQR added to 15 T2D subjects (HbA1c 8.3%) treated with a GLP-1 RA significantly improved HbA1c (-0.6%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). Plasma norepinephrine (NE), normetanephrine (NM), TBAR (a marker of systemic OS), nitrotyrosine (NT, a marker of systemic oxidative/nitrosative stress), prolactin and leptin were measured at baseline and after 4 months of BQR add-on therapy (3.2 mg/day). Plasma NE, NM, TBAR, NT and prolactin levels were elevated at baseline and decreased significantly with BQR [NE by 33% (2.95 to 1.95 ng/mL, p &amp;lt;0.0005); NM by 22% (56.5 to 44.3 pg/ml, p&amp;lt;0.018); TBAR by 10% (10.2 to 9.2 μM, p=0.04); NT by 13% (214 to 187 nM, p&amp;lt;0.02); prolactin by 42% (13.0 to 7.6 ng/ml, p&amp;lt;0.012)]. Plasma leptin, unchanged in the whole group, decreased 23% (35.7 to 27.5 ng/mL, p=0.038) in subjects with elevated leptin (&amp;gt;20 ng/dl, N=7) at baseline. Conclusion: Bromocriptine-QR is the only T2D therapy known to simultaneously reduce elevated plasma NE, NM, prolactin and OS and such actions may be important for the drug’s glucose lowering and CVD protective effects. Disclosure B. Chamarthi: Employee; Self; VeroScience LLC. E. Cersosimo: None. J.M. Adams: None. M. Alatrach: None. C. Agyin: None. C.L. Triplitt: Consultant; Self; Abbott. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. M. Ezrokhi: Employee; Self; VeroScience LLC. S. Luo: Employee; Self; VeroScience LLC. E. Duvallet: Employee; Self; VeroScience LLC. A.H. Cincotta: Employee; Self; VeroScience LLC. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.

Biomarkers of oxidative stress as an assessment of the redox status of the liver in dogs.

BackgroundOxidative stress is associated with a diverse group of liver disorders across species.ObjectivesDetermine whether glutathione (GSH) concentration in plasma and red blood cells correlates with liver GSH concentration in dogs and evaluate whether other markers of systemic oxidative stress, plasma vitamin E and urine 8‐isoprostanes/creatinine (F2‐IsoPs/Cr) concentrations, correlate with liver GSH.AnimalsThirty‐four client‐owned dogs undergoing clinically indicated liver biopsy and 15 healthy control dogs.MethodsProspective, observational cross‐sectional study. Urine and blood were collected before liver biopsy. Plasma, erythrocyte, and liver GSH were measured using high performance liquid chromatography (HPLC); vitamin E was measured by HPLC, and F2‐IsoPs/Cr was measured by gas chromatography/mass spectrometry.ResultsAll dogs were treated at the discretion of the attending clinician (24/34 received antioxidants; 4/34 fed therapeutic liver diet), which included dogs with primary or secondary liver disease (inflammatory (n = 21), metabolic (n = 9), vascular (n = 2), and neoplastic (n = 2)). Median GSH concentrations in plasma, erythrocyte, and liver were 0.18 mg/dL (range 0.14 to 0.56 mg/dL), 56.7 mg/dL (18.3 to 79.2 mg/dL), and 181 mg/dL (39.9 to 527 mg/dL), respectively. No significant correlations were found between liver GSH and erythrocyte GSH, plasma GSH, vitamin E, or F2‐IsoPs/Cr. Dogs undergoing clinically indicated liver biopsy had significantly higher urine F2‐IsoPs/Cr than did healthy controls (5.89 vs 2.98 ng/mg; P < .0001).Conclusions and Clinical ImportanceErythrocyte and plasma GSH are not indicative of liver GSH concentration in dogs. In addition, dogs undergoing clinically indicated liver biopsy have evidence of increased systemic oxidative stress compared to healthy controls.

Oxidative Stress in Animal Models of Acute and Chronic Renal Failure.

Introduction Kidney disease is a worldwide health and economic burden, with rising prevalence. The search for biomarkers for earlier and more effective disease screening and monitoring is needed. Oxidative stress has been linked to both, acute kidney injury (AKI) and chronic kidney disease (CKD). The aim of our study was to investigate whether the concentrations of systemic markers of oxidative stress and antioxidant status are affected by AKI and CKD, and to identify potential biomarkers. Methods In adult male Wistar rats, AKI was induced by bilateral nephrectomy, and CKD was induced by 5/6 nephrectomy. Blood was collected 48 hours after surgery in AKI and 6 months after surgery in CKD. Advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGEs), fructosamine, total antioxidant capacity (TAC), and ferric reducing antioxidant power (FRAP) were measured. Results Impaired renal function was confirmed by high concentrations of plasma creatinine and urea in AKI and CKD animals. AOPP and fructosamine were higher by 100% and 54% in AKI, respectively, and by 100% and 199% in CKD, respectively, when compared to corresponding control groups. Similarly, there was approximately a twofold increase in AGEs (by 92%) and TAC (by 102%) during AKI. In CKD, concentrations of FRAP, as an antioxidative status marker, were doubled (by 107%) when compared to the control group, but concentration of TAC, another marker of antioxidative status, did not differ between the groups. Conclusions AKI and CKD led to increased systemic oxidative stress. AOPP and fructosamine could be considered potential biomarkers for both, acute and chronic kidney damage. On the other hand, AGEs, TAC, and FRAP seem to be disease specific, which could help to differentiate between acute and chronic kidney injuries. However, this needs further validation in clinical studies.

Hemorrhage simulated by lower body negative pressure provokes an oxidative stress response in healthy young adults.

We characterize the systemic oxidative stress response in young, healthy human subjects with exposure to simulated hemorrhage via application of lower body negative pressure (LBNP). Prior work has demonstrated that LBNP and actual blood loss evoke similar hemodynamic and immune responses (i.e. white blood cell count), but it is unknown whether LBNP elicits oxidative stress resembling that produced by blood loss. We show that LBNP induces a 29% increase in F2-isoprostanes, a systemic marker of oxidative stress. The findings of this investigation may have important implications for the study of hemorrhage using LBNP, including future assessments of targeted interventions that may reduce oxidative stress, such as novel fluid resuscitation approaches.