Plasma Oxidative Stress Markers Research Articles

L‐arginine or tempol supplementation improves renal and cardiovascular function in rats with reduced renal mass and chronic high salt intake

Early life reduction in nephron number and chronic high salt intake cause development of renal and cardiovascular disease, which has been associated with oxidative stress and nitric oxide (NO) deficiency. We investigated the hypothesis that interventions stimulating NO signalling or reducing oxidative stress may restore renal autoregulation, attenuate hypertension and reduce renal and cardiovascular injuries following reduction in renal mass and chronic high salt intake. Male Sprague-Dawley rats were uninephrectomized (UNX) or sham-operated at 3 weeks of age and given either a normal-salt (NS) or high-salt (HS) diet. Effects on renal and cardiovascular functions were assessed in rats supplemented with substrate for NO synthase (L-Arg) or a superoxide dismutase mimetic (Tempol). Rats with UNX + HS developed hypertension and displayed increased renal NADPH oxidase activity, elevated levels of oxidative stress markers in plasma and urine, and reduced cGMP in plasma. Histological analysis showed signs of cardiac and renal inflammation and fibrosis. These changes were linked with abnormal renal autoregulation, measured as a stronger tubuloglomerular feedback (TGF) response. Simultaneous treatment with L-Arg or Tempol restored cGMP levels in plasma and increased markers of NO signalling in the kidney. This was associated with normalized TGF responses, attenuated hypertension and reduced signs of histopathological changes in the kidney and in the heart. Reduction in nephron number during early life followed by chronic HS intake is associated with oxidative stress, impaired renal autoregulation and development of hypertension. Treatment strategies that increase NO bioavailability, or reduce levels of reactive oxygen species, were proven beneficial in this model of renal and cardiovascular disease.

Acute (but not chronic) smoking paradoxically protects the endothelium from ischemia and reperfusion: insight into the “smoking paradox”

The negative impact of cigarette smoking on the cardiovascular system has been recognized for more than 50 years. Smoking is associated with increased heart rate and sympathetic outflow, inflammation, with accelerated progression of atherosclerosis, enhanced platelet aggregation, decreased fibrinolytic activity, endothelial dysfunction, worsening of renal function [1], and ultimately with increased hospitalizations for myocardial infarction, stroke and heart failure [2, 3]. Importantly, many of these effects are felt to be mediated, at least in part, by increased exposure to reactive oxygen species. This concept is supported by increased plasma markers of oxidative stress and by the observation that administration of antioxidants such as vitamin C reverses the vascular abnormalities associated with smoking [4]. The irrefutable evidence of higher ischemic rates in smokers stands in contrast with several large epidemiological studies demonstrating that, among patients who experience a myocardial infarction, those who smoke appear to have lower mortality and morbidity [5–7]. Some authors have argued that this observation is due to differences between the populations studied [6]; other studies found that in patients with infarction, smoking remains associated with reduced mortality even after controlling for age, infarct size, clinical presentation, blood pressure, cardiovascular risk factors and several other parameters [7, 8]. The complex mechanisms triggered by reactive oxygen species might contribute to explain this smoker’s paradox. While having a crucial role in the pathophysiology and progression of cardiovascular disease, reactive oxygen and nitrogen species are also involved in ischemic preconditioning, a protective phenomenon associated with a reduced susceptibility to ischemia and reperfusion damage [9]. We set out to investigate the impact of smokinginduced oxidative stress on the vascular-endothelial dysfunction induced by ischemia and reperfusion. Radial artery endothelium-dependent flow-mediated dilation (FMD) was measured before and after local ischemia/reperfusion (15 min ischemia by inflating a pneumatic cuff around the upper arm followed by 15 min reperfusion) in 10 healthy subjects (7 males, 25–28 years old) with no cardiac risk factors. These procedures were carried out twice, at 7-day intervals. Twenty-four hours before each visit, subjects underwent, under supervision and in randomized order, two protocols: in the first protocol, they smoked two cigarettes (nicotine content 1.2 mg, tar 16 mg, CO 14 mg) 15 min after receiving 2 g of intravenous vitamin C. In the second protocol, they smoked two cigarettes 15 min after receiving an intravenous placebo (10 ml of normal saline). Subjects were occasional smokers (0–2 cigarettes/month), and none of them had smoked in the previous 7 days. A separate group of 10 smokers (7 males, age 24–28 years, 3–10 cigarettes/day) underwent the same FMD-IR-FMD protocol after a 24-h non-smoking interval. The methods for the assessment of FMD in our laboratory have been previously described [9]. Briefly, the diameter of the radial artery is measured in M. Lisi S. Dragoni M. C. Leone Department of Internal, Cardiovascular and Geriatric Medicine, University of Siena, Siena, Italy

Sex differences of oxidative stress markers in young healthy subjects are marker-specific in plasma but not in saliva

Background: Several studies showed there are sex differences in oxidative stress. An observational study analysing oxidative stress markers in young healthy men and women is lacking. Moreover, it is unclear whether the differences are related to sex hormones.Aim: The primary goal was to analyse differences in oxidative stress markers with regard to sex in plasma of young healthy subjects and whether differences are related to sex hormones. The secondary study compared oxidative stress markers in plasma with salivary samples.Methods: Plasma and saliva samples were analysed from 158 young healthy probands. Established spectro-photometric/fluorometric methods were used to quantify oxidative stress markers. Sex hormones were measured using ELISA kits.Results: In plasma, malondialdehyde and advanced glycation end products were significantly higher in women. Advanced oxidation protein products and the ferric reducing ability of plasma were higher in men. Sex hormones were not associated with oxidative stress markers. In saliva, analysed markers of antioxidant status were higher in men, but no sex differences were found in other markers.Conclusion: Observed parameters showed marker-specific sex differences in plasma, but these differences were not related to sex hormones. Plasma and saliva concentrations of biomarkers did not correlate, reflecting oral but not systemic conditions.

The Effect of High-Dose Insulin Analog Initiation Therapy on Lipid Peroxidation Products and Oxidative Stress Markers in Type 2 Diabetic Patients

Effect of high-dose insulin analog initiation therapy was evaluated on lipid peroxidation and oxidative stress markers in type 2 diabetes mellitus (T2DM). Twenty-four T2DM patients with HbA1c levels above 10% despite ongoing therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs. Glycemic profiles were determined over 72 hours by Continuous Glucose Monitoring System (CGMS), and blood/urine samples were collected at 24 and 72 hours. Insulin analog plus metformin treatment significantly reduced glucose variability. Plasma and urine lipid peroxidation were markedly decreased following insulin analog plus metformin treatment. No correlation existed between glucose variability and levels of plasma and urine oxidative stress markers. Likewise, changes in mean blood glucose from baseline to end point showed no significant correlation with changes in markers of oxidative stress. On the contrary, decreased levels of oxidative stress markers following treatment with insulin analogs were significantly correlated with mean blood glucose levels. In conclusion, insulin plus metformin resulted in a significant reduction in oxidative stress markers compared with oral hypoglycemic agents alone. Data from this study suggests that insulin analogs irrespective of changes in blood glucose exert inhibitory effects on free radical formation.

Low-volume exercise training attenuates oxidative stress and neutrophils activation in older adults

The purpose of this study was to investigate the effects of low-volume exercise training (100 min/week) on oxidative stress and neutrophils activation markers in older adults. Twenty-eight older adults (age range 65-78 years) were assigned into control (n = 14) or exercise (n = 14) groups. The exercise program consisted of walking 30-60 min/session, 2 days each week for 12 weeks. Blood samples were taken before starting the sessions (baseline) and when they ended. Fasting plasma and serum oxidative stress and inflammatory markers were measured using commercial kits. Cell surface expression of adhesion molecules on circulating leukocytes (CD66b and CD62L) was determined using flow cytometry. The concentrations of derivatives of reactive oxygen metabolites tended to be lower than the baseline values only in the exercise group (P = 0.05). The biological antioxidant potential, thioredoxin concentrations, and glutathione peroxidase activities significantly increased only in the exercise group (P < 0.05 for all). While CD66b expression tended to decrease only in the exercise group, CD62L expression significantly increased (P < 0.05). Our findings indicate that exercise training below the current recommended level of at least 150 min/week attenuates basal oxidative stress and neutrophil activation in older adults. Thus, our findings may encourage more people to incorporate a small amount of physical activity into their lives.

Plasma Levels of Oxidative Stress Biomarkers and Long‐Term Cognitive Performance after Severe Head Injury

Plasma Levels of Oxidative Stress Biomarkers and Long‐Term Cognitive Performance after Severe Head Injury

Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanism

Cell-free hemoglobin (Hb) exposure may be a pathogenic mediator in the development of pulmonary arterial hypertension (PAH), and when combined with chronic hypoxia the potential for exacerbation of PAH and vascular remodeling is likely more pronounced. We hypothesized that Hb may contribute to hypoxia-driven PAH collectively as a prooxidant, inflammatory, and nitric oxide (NO) scavenger. Using programmable micropump technology, we exposed male Sprague-Dawley rats housed under room air or hypoxia to 12 or 30 mg per day Hb for 3, 5, and 7 wk. Blood pressure, cardiac output, right ventricular hypertrophy, and indexes of pulmonary vascular remodeling were evaluated. Additionally, markers of oxidative stress, NO bioavailability and inflammation were determined. Hb increased pulmonary arterial (PA) pressure, pulmonary vessel wall stiffening, and right heart hypertrophy with temporal and dose dependence in both room air and hypoxic cohorts. Hb induced a modest increase in plasma oxidative stress markers (malondialdehyde and 4-hydroxynonenal), no change in NO bioavailability, and increased lung ICAM protein expression. Treatment with the antioxidant Tempol attenuated Hb-induced pulmonary arterial wall thickening, but not PA pressures or ICAM expression. Chronic exposure to low plasma Hb concentrations (range = 3-10 μM) lasting up to 7 wk in rodents induces pulmonary vascular disease via inflammation and to a lesser extent by Hb-mediated oxidation. Tempol demonstrated a modest effect on the attenuation of Hb-induced pulmonary vascular disease. NO bioavailability was found to be of minimal importance in this model.

147 Comparative analysis of inflammatory markers in cystic fibrosis and non-cystic fibrosis bronchiectasis

Objetives: Oxidative stress is believed to play an important role in the pathophysiology of cystic fibrosis (CF). Many factors may contribute to increased oxidative stress in CF, as the disease combines the increased production of reactive oxygen species (ROS) with impaired antioxidant protection. The aim, therefore, of this study was to evaluate oxidative stress using different biomarkers (both plasma and intracellular in peripheral blood leukocytes) in a group of clinically stable adult patients with bronchiectasis (CF and non-CF) and compare the results with a group of healthy controls. Methods: This cross-sectional study included 90 patients with a diagnosis of bronchiectasis with and without CF, periodically monitored in the adult bronchiectasis/CF unit at a university hospital. A control group comprised 50 healthy subjects, matched with respect to patient sex, age and nutritional status. The intracellular oxidative stress biomarkers (mitochondrial membrane potential, superoxide anion and hydrogen peroxide and intracellular glutathione) were analyzed in white blood cells as total leukocytes, neutrophils, lymphocytes and monocytes. The plasma oxidative stress biomarkers (total antioxidant capacity, glutathione peroxidase activity, superoxide dismutase activity, catalase activity, 8-iso-prostaglandin F2a, TBARs) were measured. Conclusions: Cell and plasma markers of oxidative stress were raised in the patients with bronchiectasis as compared with the controls and no differences depending on the cause of the bronchiectasis (CF vs non-CF) were found.

Plasma Methionine Sulfoxide in Persons with Familial Alzheimer’s Disease Mutations

Background: Convergent evidence suggests that oxidative stress plays a central role in the pathology of Alzheimer’s disease (AD). We asked if consequently, oxidation of methionine residues to methionine sulfoxide (MetO) was increased in plasma proteins of persons carrying familial AD (FAD) mutations. Methods: Plasma was collected from 31 persons from families harboring PSEN1 or APP mutations. Using Western blot analysis with a novel anti-MetO polyclonal antibody, MetO levels were measured and compared between FAD mutation carriers (MCs) and non-mutation carrying (NCs) kin. Results: A MetO-positive 120-kDa gel band distinguished FAD MCs and NCs (mean 11.4 ± 2.8 vs. 4.0 ± 3.1, p = 0.02). In a subset of subjects for whom both measurements were available, MetO levels correlated well with plasma F2-isoprostane (r = 0.81, p < 0.001) and superoxide dismutase 1 (r = 0.52, p = 0.004) levels. Conclusion: Our data provide evidence for elevated MetO levels in persons carrying FAD mutations that correlate with other indices of oxidative stress and suggest that plasma oxidative stress markers may be useful for diagnosis of AD.

Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis

After NADPH oxidase mediated radical formation, hypochloric acid (HOCl) is formed when Cl is used as a substrate by the myeloperoxidase enzyme. Myeloperoxidase is secreted from H2O2 activated leukocytes with polymorphic nuclei. The generation of HOCl also causes the formation of advanced oxidation protein products (AOPP) through damage to normal tissue and protein oxidation. AOPP has been identified as a marker of inflammation in many diseases. However, AOPP has not been investigated in ulcerative colitis. As a result of mucosal inflammation in ulcerative colitis, oxidative stress can occur. We aimed to determine whether plasma AOPP and oxidative stress markers are detectable in active ulcerative colitis. The patient group consisted of 59 patients who were diagnosed with ulcerative colitis in the clinic by histology and endoscopy. The patients were hospitalised and treated in the Gastroenterology Department of Gazi University Medical Facility. The 59 patients were separated into active and inactive groups according to the endoscopic activation index (EAI). Group I consisted of 33 active ulcerative colitis patients, Group II consisted of 26 inactive ulcerative colitis patients and Group III consisted of healthy control subjects. The disease activity of these patients were measured using the Rachmilewitz EAI based on rectosigmoidoscopic or colonoscopic findings. Patients with EAI scores greater than 4 were scored as having active disease (Group I). Patients with EAI<4 were scored as being in disease remission (Group II). The control subjects (Group III) were 51 healthy individuals. The plasma AOPP levels were measured using a spectrophotometric method. There were no statistically significant differences in gender (P<0.22) and age (P<0.11) between the groups examined. The plasma AOPP level in Group I was 148.72±9.08μmol/L. The plasma AOPP level in Group II was 74.48±7.06μmol/L, and the plasma AOPP level in Group III was 64.93±2.55μmol/L. The AOPP levels in Group I were statistically different than in Group II and III (P<0.05). The AOPP levels were similar between Group II and Group III (P>0.05). The EAI value was 8.84±0.31 in Group I and 2.76±0.08 in Group II. There were statistically significant differences for EAI between groups (P<0.05). The correlation between AOPP and EAI in all patients with ulcerative colitis were statistically significant (P<0.05, r=0.61). The regression model in this correlation was statistically significant (y=49.68+10.75x, P<0.05). Based on our results, we suggest that AOPP could be used as a non invasive activation marker for ulcerative colitis patients.

Effect of α‐thalassaemia on exercise‐induced oxidative stress in sickle cell trait

Alpha-thalassaemia is known to reduce intra-erythrocyte HbS (sickle haemoglobin) concentration in sickle cell trait (SCT) subjects. Because HbS was shown to increase oxidative stress, the purpose of this study was to assess the effects of the coexistence of α-thalassaemia and SCT on oxidative stress markers and nitric oxide (NO) metabolism after an acute physical exercise. Forty subjects (age: 23.5 ± 2.21 years), SCT carriers (HbAS) or healthy subjects (HbAA), with (-αT) or without (-NαT) an associated α-thalassaemia took part in the study. Plasma markers of oxidative stress [advanced oxidation protein products (AOPP), protein carbonyl, malondialdehyde (MDA) and nitrotyrosine], anti-oxidant defences and NO metabolism (NOx) were measured at rest (T(rest)), immediately following an incremental maximal exercise test (T(ex)) and during recovery (T(1h), T(2h) and T(24h)). Malondialdehyde expressed as the percentage of changes from baseline was significantly higher in the HbAS-NαT compared with HbAS-αT during recovery (+36.3 ± 14.1% vs. -1.8 ± 13.2% at T(1h), P = 0.02; +36.6 ± 13.4% vs. -11.4 ± 12.5% at T(2h), P = 0.004 and +24.1 ± 12.3% vs. -14.4 ± 11.5% at T(24h), P = 0.02 in HbAS-NαT vs. HbAS-αT). Compared with HbAS-NαT, HbAS-αT had a higher NOx change from baseline at T(ex) (-23.4 ± 20.6% vs. +57.7 ± 19.3%, respectively; P = 0.005) and lower nitrotyrosine change from baseline at T(1h) (+7.2 ± 22.2% vs. +93.5%±29.3%, respectively; P = 0.04). All these data suggest that the presence of α-thalassaemia may blunt the higher level of oxidative stress and the impaired bioavailability of NO observed in the SCT carriers.

Grape seed extract modifies insulin resistance induced by a high fat/carbohydrate meal in metabolic syndrome patients

Insulin resistance is a characteristic feature of metabolic syndrome (MS) and is known to be associated with a relatively high postprandial plasma glucose concentration. We have shown previously that consumption of a meal that is high in readily available carbohydrates/fat causes a postprandial increase in markers of oxidative stress and insulin resistance. The present investigation was undertaken to determine whether a grape seed extract (GSE‐Meganatural© Gold) that is rich in antioxidants would modify these post‐prandial responses in individuals with the MS. After an overnight fast, twelve subjects with MS (6 men and 6 women) consumed a high‐carbohydrate, moderate‐fat meal in a cross‐over design. A GSE (300 mg) or placebo capsule was administrated 1 h before the meal. Postprandial changes in plasma insulin, glucose, oxidative stress and inflammatory markers were measured hourly for 6 h. Postprandial plasma glucose concentrations (area under the curve over 6 hr) were significantly lower when the meal was preceded by GSE compared with placebo (P=0.04). Postprandial insulin concentrations remained unchanged (P&gt;0.05). Meal‐induced increases in oxidized LDL were attenuated with GSE capsule (P&lt;0.05), whereas IL‐6 and TNF‐α concentrations were unchanged after the two treatments (P&gt;0.05). These data suggested that GSE enhances postprandial insulin sensitivity in subjects with the MS. Study was supported by Polyphenolic Inc. Madera, CA

Whole apple but not apple pectin affects cardiac pathology and the oxidative stress/antioxidant transcriptome in obese rats

Apples provide both pectin fiber and phytochemicals that may confer cardiac benefits. However, their comparative effects on hypertension and cardiac function are unknown. In the obesity‐prone Zucker Fatty rat, we compared three diets: freeze‐dried whole apple powder (APP, 10% w:w), apple pectin (PEC), or control (CON). Diets were matched for macronutrients and calories, and animals were provided equivalent food per day. Body weight, fat mass and lean mass were not significantly different among groups. However, APP caused progressive reductions in serial systolic blood pressure, while PEC only caused transient and non‐significant reductions. After 120 days, APP but not PEC reduced cardiac hypertrophy, improved diastolic function, increased cardiac output, and reduced fibrosis. APP also reduced plasma oxidative stress marker malonyldialdehyde. APP but not PEC affected the cardiac transcriptome related to pro‐inflammatory NFκB activation and to antioxidant defense. Both APP and PEC reduced cardiometabolic risk factors like serum triglycerides, total cholesterol and fasting glucose but increased fecal cholesterol and bile acid content. Results suggest that diet‐altered lipid and glucose handling did not reduce cardiac pathology. In addition, reduced tissue oxidative stress by whole apple may be critical to cardiac‐specific effects; apple‐derived phytochemicals may mediate these benefits.

Cyclooxygenase‐2 inhibition prevent angiotensin II‐induced oxidative stress but not hypertension in humans

Angiotensin II (AngII) is known as an important oxidative stress mediator in hypertension. There is controversy whether cyclooxygenase‐2 (COX‐2) specific inhibitors would be associated with elevations or decrease in blood pressure (BP) despite evidences showing decrease in ROS generation under COX‐2 inhibition. The aim of this study was to determine in healthy humans whether the COX‐2 selective inhibitor celecoxib has antioxidant and hypertensive protective effects against AngII. BP and selected plasma oxidative stress markers (8OHdG; AOPP), peroxynitrite activity (nitrotyrosine), endothelin‐1 (ET1) and nitric oxide metabolism (NOx) were measured at baseline and in response to a graded infusion of AngII before and after 14 days of celecoxib in 14 healthy subjects in high‐salt balance. In response to AngII challenge, all markers of oxidative stress were increased and there was blunting of NOx. Though no effect was observed in terms of BP response to AngII challenge, celecoxib significantly attenuated the increase in oxidative stress as observed by a reduction in the rise of 8OHdG, nitrotyrosine, aldosterone and the NOx inhibition induced by AngII infusion. In conclusion, exposure to AngII increases oxidative stress in humans, though this AngII‐mediated upregulation is attenuated with COX‐2 inhibition. Supported by Alberta Innovates Health Solutions and Canadian Institutes for Health Research.

Inter-relationship of plasma markers of oxidative stress and thyroid hormones in schizophrenics

BackgroundThe relationship of oxidative stress to thyroid hormones has not been studied in the schizophrenics. The present study determined the status and interrelationship of plasma markers of oxidative stress, nitric oxide and thyroid hormones in thirty (17 males and 13 females) newly diagnosed patients with acute schizophrenia before initiation of chemotherapy. Twenty five (13 males and 12 females) mentally healthy individuals served as controls. Patients and controls with history of hard drugs (including alcohol and cigarette), pre-diagnosis medications (e.g. antiparkinsonian/antipsychotic drugs), chronic infections, liver disease and diabetes mellitus were excluded from the study. Plasma levels of total antioxidant potential (TAP), total plasma peroxides (TPP), nitric oxide (NO), malondialdehyde (MDA), thyroxine (T4), tri-iodothyronine (T3) and thyroid stimulating hormone (TSH) were determined in all participants using spectrophotometric and enzyme linked immunosorbent assay (ELISA) methods respectively. Oxidative stress index (OSI) was calculated as the percent ratio of total plasma peroxides and total antioxidant potential.FindingsSignificantly higher plasma levels of MDA (p < 0.01), TPP (p < 0.01), OSI (p < 0.01), T3 (p < 0.01) and T4 (p < 0.05) were observed in schizophrenics when compared with the controls. The mean levels of TAP, NO and TSH were significantly lower in schizophrenics (p < 0.01) when compared with the controls. The result shows that T3 values correlate significantly with MDA (p < 0.05) and TPP (p < 0.01) in schizophrenics.ConclusionsHigher level of TPP may enhance thyroid hormogenesis in schizophrenics. Adjuvant antioxidant therapy may be a novel approach in the treatment of schizophrenic patients.

Nitro-Oxidative Stress Biomarkers in Active and Inactive Men

Oxidative stress markers are novel factors shown to be related to cardiovascular (CVD) risk. We examined the effects of long-term exercise, age, and their interaction on plasma oxidized LDL (ox-LDL), nitrotyrosine, and myeloperoxidase (MPO) levels, all biomarkers of oxidative stress, and determined their association with plasma nitric oxide (NOx) levels as an index of NO bioavailability. Older (62±2 yr) active men (n=12) who had exercised for >30 years and young (25±4 yr) active men (n=7) who had exercised for >3 years were age- and BMI-matched to older (n=11) and young (n=8) inactive men. Young subjects had lower plasma nitrotyrosine levels than older subjects (P=0.047). Young inactive subjects had higher ox-LDL levels than either the young active (P=0.042) or the older active (P=0.041) subjects. In addition, plasma oxidative stress levels, particularly ox-LDL, were correlated with various conventional plasma lipoprotein-lipid levels, and in older subjects were associated with Framingham risk score (r=0.49, P=0.015). We found no relationships between plasma oxidative stress markers and NOx levels. The findings suggest that a sedentary lifestyle may be associated with higher ox-LDL levels and that the levels of oxidative stress markers are related to levels of other conventional CVD risk factors and overall CVD risk.

Research in athletes with sickle cell trait: just do it

the sickle cell trait (SCT) genotype, a condition found in an estimated 300 million people worldwide and 8–9% of African Americans is characterized by the heterozygous inheritance of a single defective beta globin gene. Inherited in the homozygous form, the beta globin gene mutation leads to

Allopurinol Intake Does Not Modify the Slow Component of V O2 Kinetics and Oxidative Stress Induced by Severe Intensity Exercise

The aim of this study was to test the hypothesis that allopurinol ingestion modifies the slow component of V(.)O(2) kinetics and changes plasma oxidative stress markers during severe intensity exercise. Six recreationally active male subjects were randomly assigned to receive a single dose of allopurinol (300 mg) or a placebo in a double-blind, placebo-controlled crossover design, with at least 7 days washout period between the two conditions. Two hours following allopurinol or placebo intake, subjects completed a 6-min bout of cycle exercise with the power output corresponding to 75 % V(.)O(2)max. Blood samples were taken prior to commencing the exercise and then 5 minutes upon completion. Allopurinol intake caused increase in resting xanthine and hypoxanthine plasma concentrations, however it did not affect the slow component of oxygen uptake during exercise. Exercise elevated plasma inosine, hypoxanthine, and xanthine. Moreover, exercise induced a decrease in total antioxidant status, and sulfhydryl groups. However, no interaction treatment x time has been observed. Short term severe intensity exercise induces oxidative stress, but xanthine oxidase inhibition does not modify either the kinetics of oxygen consumption or reactive oxygen species overproduction.

Coenzyme Q Metabolism Is Disturbed in High Fat Diet-Induced Non Alcoholic Fatty Liver Disease in Rats

Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by >2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

Blockade of the Nuclear Factor-κB Pathway in the Endothelium Prevents Insulin Resistance and Prolongs Life Spans

Nuclear factor-κB (NF-κB) signaling plays critical roles in physiological and pathological processes such as responses to inflammation and oxidative stress. To examine the role of endothelial NF-κB signaling in vivo, we generated transgenic mice expressing dominant-negative IκB under the Tie2 promoter/enhancer (E-DNIκB mice). These mice exhibited functional inhibition of NF-κB signaling specifically in endothelial cells. Although E-DNIκB mice displayed no overt phenotypic changes when young and lean, they were protected from the development of insulin resistance associated with obesity, whether diet- or genetics-induced. Obesity-induced macrophage infiltration into adipose tissue and plasma oxidative stress markers were decreased and blood flow and mitochondrial content in muscle and active-phase locomotor activity were increased in E-DNIκB mice. In addition to inhibition of obesity-related metabolic deteriorations, blockade of endothelial NF-κB signaling prevented age-related insulin resistance and vascular senescence and, notably, prolonged life span. These antiaging phenotypes were also associated with decreased oxidative stress markers, increased muscle blood flow, enhanced active-phase locomotor activity, and aortic upregulation of mitochondrial sirtuin-related proteins. The endothelium plays important roles in obesity- and age-related disorders through intracellular NF-κB signaling, thereby ultimately affecting life span. Endothelial NF-κB signaling is a potential target for treating the metabolic syndrome and for antiaging strategies.