8-epi-prostaglandin-f2alpha and Chronic-Disease

The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women.

Topics: Aged; Arizona; Biomarkers; Body Mass Index; C-Reactive Protein; Carotenoids; Chronic Disease; Cross-Over Studies; Dinoprost; Female; Humans; Lysine; Middle Aged; Obesity; Overweight; Oxidative Stress; Postmenopause; Risk Factors; Vegetables

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Benzimidazoles; Benzoates; Chronic Disease; Cilazapril; Creatinine; Cross-Over Studies; Dinoprost; Diuretics; Female; Humans; Hydrochlorothiazide; Kidney Diseases; Male; Mineralocorticoid Receptor Antagonists; Oxidative Stress; Spironolactone; Telmisartan

Tempol, a superoxide dismutase-mimetic drug, has been shown to attenuate radical-induced damage, exerting beneficial effects in the animal models of oxidative stress and hypertension. This study evaluated the effect of Tempol on renal structural and functional alterations in two-Kidney, one-Clip hypertensive rats. In this study, young male Wistar rats had the left kidney clipped (2K1C), and sham-operated animals (Sham) were used as controls. Animals received Tempol (1mmol/L in drinking water) or vehicle for 5 weeks. Systolic blood pressure was evaluated once a week. At the end of the experimental protocol, the animals were placed in metabolic cages to collect urine (24h) and then anesthetized with thiopental (70mg/kg i.p.) to collect blood by puncturing the descending aorta for biochemical analysis, and the clipped kidney for morphological and immunohistochemical analyses. The vasodilator effect of Tempol was evaluated in mesenteric arterial bed (MAB) isolated from adult Wistar rats. The chronic treatment with Tempol prevented the development of hypertension and the increased plasma levels of urea, creatinine, and 8-isoprostane in 2K1C animals. Tempol also improved both glomeruli number and kidney volume to normal levels in the 2K1C+Tempol group. In addition, the treatment prevented the increased collagen deposition and immunostaining for renin, caspase-3, and 8-isoprostane in the stenotic kidney of 2K1C animals. Moreover, Tempol induced a dose-dependent vasodilator response in MAB from Wistar rats. These results suggest that Tempol protects the stenotic kidney against chronic ischemic renal injury and prevents renal dysfunction in the 2K1C model, probably through its antioxidant, vasodilator and antihypertensive actions.

Topics: Animals; Antioxidants; Biomimetic Materials; Blood Pressure; Caspase 3; Chronic Disease; Creatinine; Cyclic N-Oxides; Dinoprost; Hypertension; Ischemia; Kidney; Kidney Diseases; Kidney Glomerulus; Male; Oxidative Stress; Rats; Rats, Wistar; Renin; Spin Labels; Superoxide Dismutase; Urea; Vasodilation

Inflammatory processes, including respiratory symptoms, can be induced among workers in composting plants exposed to bioaerosols containing microorganisms and their compounds. We evaluated inflammatory processes in the lower respiratory tract via cellular and soluble mediator profiles in induced sputum (IS). IS samples of 140 current (35% smokers) and 49 former compost workers (29% smokers) as well as 29 white-collar workers (17% smokers) were collected and analyzed for the cell count and composition, and for soluble biomarkers. Significant differences between current and former compost workers and white-collar workers were detected for total cell count (p=0.0004), neutrophils (p=0.0045), sCD14 (p=0.008), and 8-isoprostane (p<0.0001). IS of non-smoking former compost workers showed lower concentrations of IL-8, total protein, immunoreactive MMP-9 and sCD14, compared with non-smoking current compost workers. 10.1% of the study population was suffering from chronic bronchitis with significant differences (p=0.018) between former compost workers (24.5%), current workers (5%), and white-collar workers (10.3%). Significantly lower IL-8 (p=0.0002), neutrophils (p=0.001), and MMP-9 (p=0.0023) values were measured in healthy subjects compared with subjects with chronic bronchitis. In conclusion, changes in lower airways were detected by analysis of biomarkers in IS of current exposed and, to a lesser extent, in IS of former compost workers. These effects are especially pronounced in subjects with chronic bronchitis.

Topics: Adult; Air Pollutants, Occupational; Biomarkers; Blood Proteins; Bronchitis; Cell Count; Chronic Disease; Cross-Sectional Studies; Dinoprost; Female; Humans; Interleukin-8; Lipopolysaccharide Receptors; Male; Matrix Metalloproteinase 9; Middle Aged; Neutrophils; Occupational Exposure; Pneumonia; Smoking; Soil; Sputum

Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low-dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11-dehydro-TXB2) is predictive of vascular events in high-risk patients. Myeloid-related protein (MRP)-8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP-14 has emerged as a powerful predictor of ACS.. We enrolled 68 stable ischemic heart disease (IHD) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP-8/14 release in the circulation is related to TX-dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low-dose aspirin-treated ACS patients. In ACS patients, plasma MRP-8/14 and urinary 11-dehydro-TXB2 levels were linearly correlated (r=0.651, P<0.001) but significantly higher than those in IHD patients (P=0.012, P=0.044) only among subjects not receiving aspirin. In aspirin-treated ACS patients, MRP-8/14 and 11-dehydro-TXB2 were lower versus those not receiving aspirin (P<0.001) and still significantly correlated (r=0.528, P<0.001). Higher 11-dehydro-TXB2 significantly predicted higher MRP-8/14 in both all ACS patients and ACS receiving aspirin (P<0.001, adj R(2)=0.463 and adj R(2)=0.497) after multivariable adjustment. Conversely, plasma MRP-8/14 (P<0.001) and higher urinary 8-iso-prostaglandin F2α (P=0.050) levels were significant predictors of residual, on-aspirin, TX biosynthesis in ACS (adjusted R(2)=0.384).. Circulating MRP-8/14 is associated with TX-dependent platelet activation in ACS, even during low-dose aspirin treatment, suggesting a contribution of residual TX to MRP-8/14 shedding, which may further amplify platelet activation. Circulating MRP-8/14 may be a target to test different antiplatelet strategies in ACS.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Calgranulin A; Calgranulin B; Chronic Disease; Dinoprost; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Platelet Activation; Platelet Aggregation Inhibitors; Thromboxane B2

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Disease; Affect; Aged; Anticipation, Psychological; Caregivers; Case-Control Studies; Chronic Disease; Deoxyguanosine; Dinoprost; DNA Damage; Female; Guanosine; Humans; Hydrocortisone; Middle Aged; Oxidative Stress; Resilience, Psychological; Saliva; Secretory Rate; Spouses; Stress, Psychological; Surveys and Questionnaires

Chronic liver diseases are commonly associated with tissue hypoxia that may cause inflammation, oxidative stress, liver cell injury and increased nuclear transcriptional regulation. The hepatic response to chronic hypoxia at the molecular level has not yet been clearly understood until now. The aim of this study is to investigate whether nuclear transcription factors [hypoxia-inducible factor-1 (HIF-1α), activator protein-1 (AP-1), nuclear factor-kappa B (NF-κB)] exhibit activity changes during hepatic response to chronic hypoxia. Blood and liver samples were collected from adult Sprague-Dawley rats living in atmospheric air or 10% oxygen for four weeks. Levels of serum alanine aminotransferase (ALT), 8-isoprostane and nitrotyrosine were measured. The activities of nuclear transcription factors and the expression of downstream genes (iNOS, eNOS, ET-1 and VEGF) were measured using RT-PCR, Western blotting and Gel shift analysis. Results showed that serum ALT level, 8-isoprostane level and formation of nitrotyrosine were within normal range at all time-points. In the hypoxic liver, DNA-binding activities of HIF-1α, NF-κB and AP-1 increased significantly. Expression levels of iNOS, VEGF and ET-1 progressively increased from day 7 to day 28. eNOS was also elevated in the hypoxic liver. In conclusion, our study suggests that increased activity of HIF-1α, AP-1 and NF-κB may partly play a significant role in the hepatic response to oxidative stress and liver injury under chronic hypoxia. The increased expression of VEGF, ET-1, iNOS and eNOS may be partly due to the compensatory mechanism in the vascular beds of the liver in response to chronic hypoxia.

Topics: Alanine Transaminase; Animals; Biomarkers; Blotting, Western; Chronic Disease; Dinoprost; Disease Models, Animal; Electrophoretic Mobility Shift Assay; Endothelin-1; Gene Expression Regulation; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Liver; Male; NF-kappa B; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Transcription Factor AP-1; Tyrosine; Vascular Endothelial Growth Factor A

The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma. Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements. Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03-0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects. Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma.

Topics: Adult; Asthma; Breath Tests; Bronchial Provocation Tests; Case-Control Studies; Chronic Disease; Cohort Studies; Cough; Dinoprost; Exhalation; Female; Humans; Hyperventilation; Male; Middle Aged; Oxidative Stress; Reference Values; Severity of Illness Index; Spirometry; Statistics, Nonparametric

We aimed to study the relationship between markers of oxidative lipid or protein damage and ventricular remodeling and the validity of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) as an indicator of disease severity in patients with ischemic chronic heart failure (CHF).. We enrolled four groups of 12 patients with varying CHF according to the New York Heart Association (NYHA) classification and 25 controls. Urinary 8-epi-PGF(2alpha) and plasma malondialdehyde and protein thiol (P-SH) groups were correlated with echocardiographic indices of remodeling. The reliability of isoprostanes was analyzed by a receiver operating characteristics (ROC) curve.. NYHA class III and IV patients exhibited elevated 8-epi-PGF(2alpha) levels, increased malondialdehyde concentrations and decreased P-SH groups when compared to controls and NYHA I and II patients. 8-Epi-PGF(2alpha) and P-SH groups correlated significantly with indices of remodeling. The ROC curve drawn for 8-epi-PGF(2alpha) allowed us to differentiate NYHA class III and IV patients from NYHA class I and II patients with a sensitivity of 95.8% and specificity of 95.8% (cut off 0.84 ng/mg creatinine; area under curve 0.99; P < 0.001).. Markers of oxidative damage are unlikely to play a significant role in early stages of CHF. However, they might become important in the course of CHF when their concentrations reach critical levels. Urinary 8-epi-PGF(2alpha) is a reliable indicator of symptomatic CHF.

Topics: Aged; Chronic Disease; Dinoprost; Disease Progression; Echocardiography; Female; Heart Failure; Humans; Isoprostanes; Lipids; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Ventricular Remodeling

Xanthine oxidase (XO)-derived reactive oxygen species (ROS) formation contributes to experimental chronic hypoxic pulmonary hypertension in adults, but its role in neonatal pulmonary hypertension has received little attention. In rats chronically exposed to hypoxia (13% O(2)) for 14 days from birth, we examined the effects of ROS scavengers (U74389G 10 mg.kg(-1).day(-1) or Tempol 100 mg.kg(-1).day(-1) ip) or a XO inhibitor, Allopurinol (50 mg.kg(-1).day(-1) ip). Both ROS scavengers limited oxidative stress in the lung and attenuated hypoxia-induced vascular remodeling, confirming a critical role for ROS in this model. However, both interventions also significantly inhibited somatic growth and normal cellular proliferation in distal air spaces. Hypoxia-exposed pups had evidence of increased serum and lung XO activity, increased vascular XO-derived superoxide production, and vascular nitrotyrosine formation. These changes were all prevented by treatment with Allopurinol, which also attenuated hypoxia-induced vascular remodeling and partially reversed inhibited endothelium-dependent arterial relaxation, without affecting normal growth and proliferation. Collectively, our findings suggest that XO-derived superoxide induces endothelial dysfunction, thus impairing pulmonary arterial relaxation, and contributes to vascular remodeling in hypoxia-exposed neonatal rats. Due to the potential for adverse effects on normal growth, targeting XO may represent a superior "antioxidant" strategy to ROS scavengers for neonates with pulmonary hypertension.

Topics: Acetylcholine; Allopurinol; Animals; Animals, Newborn; Cell Proliferation; Chronic Disease; Cyclic N-Oxides; Dinoprost; Free Radical Scavengers; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; In Vitro Techniques; Lung; Nitric Oxide Synthase Type III; Organ Size; Oxidative Stress; Pregnatrienes; Pulmonary Artery; Rats; Reactive Oxygen Species; Spin Labels; Superoxides; Time Factors; Xanthine Oxidase

The aim of this study was to contribute to the knowledge concerning pathogenesis of inflammatory chronic prostatitis by revealing possible shifts in the balance of markers of oxidative stress and anti-oxidative activity in case of leucocytospermic prostatitis. We also attempted to identify possible relations between seminal micro-organisms and oxidative stress parameters. A many-sided complex of local (spermatozoa, seminal plasma) and general (blood, urine) markers in 21 prostatitis patients and nine controls was compared. In both spermatozoa and seminal plasma, the content of diene conjugates was significantly higher in prostatitis patients compared with healthy controls. At the same time total anti-oxidative status in spermatozoa and total anti-oxidative activity in seminal plasma were lower in prostatitis patients than in controls. In urine, the level of 8-isoprostanes was significantly higher in prostatitis patients than in healthy controls, correlating well with 8-hydroxy-2'-deoxyguanosine. The latter correlated with cellular Fe and Ni contents as well, confirming that these metals with varying valency may cause DNA damage. Reduced glutathione showed higher levels in blood of controls than in prostatitis patients. Coryneform bacteria appeared to be associated with prostatitis-related oxidative stress. In conclusion, leucocytospermic prostatitis patients are characterised by oxidative stress at all levels: systemic (general), seminal plasma and cellular.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Ascorbic Acid; Case-Control Studies; Chronic Disease; Corynebacterium; Deoxyguanosine; Dinoprost; Glutathione; Humans; Interleukin-6; Leukocytes; Male; Metals; Oxidation-Reduction; Oxidative Stress; Prospective Studies; Prostatitis; Reactive Oxygen Species; Semen; Spermatozoa

Experiments were designed to test the hypothesis that antioxidant treatment would increase the anti-hypertensive actions of endogenous kinins during angiotensin converting enzyme (ACE) inhibition. Four groups of rats, all given angiotensin II (Ang II) for 2 weeks, were studied: 1) control, 2) enalapril, 3) tempol or 4) both tempol and enalapril. Ang II significantly increased systolic blood pressure (BP) when compared with the baseline (170+/-8 vs. 128+/-4 mm Hg, P<0.05). Neither enalapril nor tempol alone was able to attenuate the elevation in BP (165+/-7 and 164+/-6 mm Hg, respectively). In contrast, combined administration of tempol and enalapril prevented the increase in BP (137+/-5 mm Hg). Plasma 8-isoprostane increased in Ang II-infused rats when compared with control untreated rats (69+/-14 vs. 23+/-0.5 pg/ml, P<0.05). Tempol alone or tempol plus enalapril significantly attenuated the increase in plasma 8-isoprostane (29+/-6 and 34+/-7 pg/ml, respectively). In additional experiments, we used the bradykinin B(2) antagonist, icatibant to determine if increased B(2) receptor contributes to the anti-hypertensive effect of combined tempol and enalapril in Ang II-infused rats. Icatibant decreased the ability of this combination to lower arterial pressure. Additionally, a significant increase in B(1) receptor protein expression in renal cortex of Ang II-infused rats was observed compared to control suggesting that bradykinin receptor activation could account for the effect of enalapril to enhance the actions of tempol. These data support the hypothesis that combined reduction of superoxide along with enhanced endogenous kinins may facilitate blood pressure lowering in Ang II hypertension.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Bradykinin; Chronic Disease; Cyclic N-Oxides; Dinoprost; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Enalapril; Hydrogen Peroxide; Hypertension; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley; Receptors, Bradykinin; Spin Labels; Superoxides; Time Factors

Glycemic disorders, one of the main risk factors for cardiovascular disease, are associated with activation of oxidative stress.. To assess the respective contributions of sustained chronic hyperglycemia and of acute glucose fluctuations to oxidative stress in type 2 diabetes.. Case-control study of 21 patients with type 2 diabetes (studied 2003-2005) compared with 21 age- and sex-matched controls (studied in 2001) in Montpellier, France.. Oxidative stress, estimated from 24-hour urinary excretion rates of free 8-iso prostaglandin F2alpha (8-iso PGF2alpha). Assessment of glucose fluctuations was obtained from continuous glucose monitoring system data by calculating the mean amplitude of glycemic excursions (MAGE). Postprandial contribution to glycemic instability was assessed by determining the postprandial increment of glucose level above preprandial values (mean postprandial incremental area under the curve [AUCpp]). Long-term exposure to glucose was estimated from hemoglobin A1c, from fasting glucose levels, and from mean glucose concentrations over a 24-hour period.. Mean (SD) urinary 8-iso PGF2alpha excretion rates were higher in the 21 patients with diabetes (482 [206] pg/mg of creatinine) compared with controls (275 [85] pg/mg of creatinine). In univariate analysis, only MAGE (r = 0.86; P<.001) and AUCpp (r = 0.55; P = .009) showed significant correlations with urinary 8-iso PGF2alpha excretion rates. Relationships between 8-iso PGF2alpha excretion rates and either MAGE or AUCpp remained significant after adjustment for the other markers of diabetic control in multiple linear regression analysis (multiple R2 = 0.72 for the model including MAGE and multiple R2 = 0.41 for the model including AUCpp). Standardized regression coefficients were 0.830 (P<.001) for MAGE and 0.700 (P = .003) for AUCpp.. Glucose fluctuations during postprandial periods and, more generally, during glucose swings exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia. The present data suggest that interventional trials in type 2 diabetes should target not only hemoglobin A1c and mean glucose concentrations but also acute glucose swings.

Topics: Aged; Blood Glucose; Case-Control Studies; Chronic Disease; Diabetes Mellitus, Type 2; Dinoprost; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Linear Models; Male; Middle Aged; Oxidative Stress

Chronic oxygen exposure in the newborn rat results in lung isoprostane formation, which may contribute to the pulmonary hypertension evident in this animal model. The purpose of this study was to investigate the pulmonary arterial smooth muscle responses to 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2a)) in newborn rats exposed to 60% O2 for 14 days. Because, in the adult rat, 8-iso-PGF(2alpha) may have a relaxant effect, mediated by nitric oxide (NO), we also sought to evaluate the pulmonary arterial NO synthase (NOS) protein content and NO release in the newborn exposed to chronic hyperoxia. Compared with air-exposed control animals, 8-iso-PGF(2a) induced a significantly greater force (P < 0.01) and reduced (P < 0.01) relaxation of precontracted pulmonary arteries in the 60% O2-treated animals. These changes were reproduced in control pulmonary arteries by NOS blockade by using NG-nitro-L-arginine methyl ester. Pulmonary arterial endothelial NOS was unaltered, but the inducible NOS protein content was significantly decreased (P < 0.01) in the experimental group. Pulmonary (P < 0.05) and aortic (P < 0.01) tissue ex vivo NO accumulation was significantly reduced in the 60% O2-treated animals. We speculate that impaired pulmonary vascular tissue NO metabolism after chronic O2 exposure potentiates 8-iso-PGF(2alpha)-induced vasoconstriction in the newborn rat, thus contributing to pulmonary hypertension.

Topics: Animals; Animals, Newborn; Chronic Disease; Dinoprost; Female; Hyperoxia; Hypertension, Pulmonary; Isoprostanes; Muscle, Smooth, Vascular; Nitric Oxide; Nitric Oxide Synthase; Oxygen; Pregnancy; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Vasoconstrictor Agents

8-Isoprostaglandin F2alpha is one of a series of isoprostanes formed by free radical catalysed peroxidation of arachidonic acid. Urinary 8-isoprostaglandin F2alpha is a new marker which reflects oxidative stress in vivo and can be utilized as a diagnostic tool to assess the extent of oxidative stress in various disease states associated with lipid peroxidation. Increased levels of 8-isoprostaglandin F2alpha in cardiac ischemia/reperfusion provide evidence for oxidative stress during coronary perfusion. In animal studies, the restoration of blood flow after lower limb ischemia is followed by reperfusion syndrome. In this study we investigated whether lower limb ischemia/reperfusion is associated with oxidative stress, as reflected by urinary levels of 8-isoprostaglandin F2alpha. Ten patients (mean age 72 years, range 61-82 years) suffering from chronic lower limb ischemia and 10 healthy volunteers (mean age 69 years, range 60-79 years) participated in the study. In all patients, diagnostic angiography had revealed stenosis or occlusion either in the aortoiliac or femoropopliteal region. Surgical revascularization consisted of femoropopliteal reconstruction, femorofemoral reconstruction, aortobifemorial reconstruction, or femoral endartectomy. Urine samples from patients were collected a day before surgery and in the second postoperative day. Urinary 8-isoprostaglandin F2alpha was extracted on a C2 silica cartridge and determinated by radioimmunoassay. After revascularization, 8-isoprostaglandin F2alpha excretion (pg/micromol creatinine, mean +/- SD) was decreased by 2.5-fold (preoperative 48.9 +/- 8.9, postoperative 19.1 +/- 9.5, P < 0.001). The postoperative values were similar to the concentrations measured in healthy volunteers (18.0 +/- 11.0). All revascularizations were successful, and the increase in ankle-brachial index (preoperative 0-0.6, postoperative 0.4-0.8) revealed improved blood flow in the ischemic lower limb. We suggest that, as assessed by the quantitation of urinary 8-isoprostaglandin F2alpha, chronic lower limb ischemia is associated with increased oxidative stress, which is decreased by revascularization.

Topics: Aged; Aged, 80 and over; Chronic Disease; Dinoprost; Female; Free Radical Scavengers; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Myocardial Revascularization; Oxidative Stress; Radioimmunoassay

Recent reports have indicated that endothelin-induced vasoconstriction in isolated aortic vascular rings may be mediated by the production of superoxide anion. The purpose of this study was to determine the role of superoxide anion in mediating the chronic renal and hypertensive actions of endothelin. Endothelin-1 (5 pmol/kg per minute) was chronically infused into the jugular vein by use of mini-osmotic pump for 9 days in male Sprague-Dawley rats and in rats treated with the superoxide anion scavenger tempol (30 mg/kg per day). Mean arterial pressure in the endothelin-1-treated rats was 141+/-3 mm Hg, compared with 125+/-2 mm Hg in control rats. Endothelin-1 increased renal vascular resistance (15.3+/-2.5 versus 10+/-1.3 mm Hg/mL per minute) and decreased renal plasma flow (6.5+/-0.9 versus 8.7+/-0.7 mL/min) in control rats. Endothelin-1 also significantly increased TBARS in the kidney and urinary 8-isoprostaglandin F2alpha excretion. The increase in arterial pressure in response to endothelin-1 was completely abolished by tempol (127+/-4 versus 127+/-4 mm Hg). Tempol also markedly attenuated the renal plasma flow and renal vascular resistance response to endothelin-1. Tempol also significantly decreased the level of 8-isoprostaglandin F2alpha in the endothelin-1-treated rats. Tempol had no effect on arterial pressure or renal hemodynamics in control rats. These data indicate that formation of reactive oxygen species may play an important role in mediating hypertension induced by chronic elevations in endothelin.

Topics: Animals; Cells, Cultured; Chronic Disease; Cyclic N-Oxides; Dinoprost; Endothelin-1; F2-Isoprostanes; Free Radical Scavengers; Hemodynamics; Hypertension; Kidney; Male; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Spin Labels; Superoxides; Thiobarbituric Acid Reactive Substances; Vasoconstrictor Agents

The purpose of this study was to determine differences in iron and iron protein (ferritin and transferrin) levels in chronic venous ulcers and acute wounds. The deleterious effect of iron in free-radical-induced tissue damage was indirectly examined by assessing 8-isoprostane levels and antioxidant status in wound fluid samples. Wound fluid samples from chronic leg ulcers in nonhealing and healing phases and wound fluid from mastectomy wounds were assayed for ferritin, transferrin, total iron, 8-isoprostane, and total antioxidant status. Immunohistochemistry and Perls' staining were performed on paired biopsies from chronic leg ulcers and on normal skin biopsies. Chronic wound fluid had significantly greater levels of ferritin (p < 0.05) and lower levels of transferrin (p < 0.001) than acute wound fluid and there was a significant reduction in the level of ferritin in healing compared to nonhealing chronic leg ulcers (p < 0.05). No significant differences were observed in the levels of total iron present in the wound fluids. Histologic staining showed consistently more ferritin and ferric iron in chronic wound tissue than in normal skin. Elevated levels of 8-isoprostane and antioxidants were observed for chronic wound fluid compared to acute wound fluid (p < 0.001). These results suggest the existence of an environment of oxidative stress in chronic wounds and the likely contribution of iron to exacerbating tissue damage and delaying healing in these wounds.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antioxidants; Biopsy; Chronic Disease; Dinoprost; Extracellular Fluid; F2-Isoprostanes; Female; Ferritins; Ferrozine; Humans; Indicators and Reagents; Iron; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Transferrin; Varicose Ulcer

In heaves-affected horses the relation between oxidant status, airway inflammation (AI) and pulmonary function (PF) is unknown. The oxidant status of blood and pulmonary epithelial lining fluid (PELF) of healthy (H, n = 6) and heaves-affected horses in clinical remission (REM, n = 6) and in crisis (CR, n = 7) was assessed at rest, during and after standardised exercise test by measurement of reduced and oxidised glutathione, glutathione redox ratio [GRR%]; uric acid and 8-epi-PGF2alpha. Oxidant status was related to PF parameters (mechanics of breathing and arterial blood gas tension) and Al parameters (bronchoalveolar lavage [BAL] neutrophil % and AI score). Haemolysate glutathione was significantly different between groups and was correlated with PF and AI parameters; GRR in PELF was increased during CR and was correlated with PF and AI parameters. Exercise induced an increase of plasma uric acid that was significantly higher both in REM and CR. PELF 8-epi-PGF2alpha was significantly increased in CR and correlated with PF and AI parameters. These results suggest that oxidative stress occurring in heaves is correlated with PF and AI and may be locally assessed by PELF glutathione status, uric acid and 8-epi-PGF2alpha. Systemic repercussions are reflected by assay of GSH in resting horses and by uric acid in exercising horses.

Topics: Animals; Bronchoalveolar Lavage Fluid; Chronic Disease; Dinoprost; F2-Isoprostanes; Glutathione; Glutathione Disulfide; Horse Diseases; Horses; Inflammation; Lung; Neutrophils; Oxidation-Reduction; Physical Conditioning, Animal; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Uric Acid