Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients.

Oxidative stress has an important role in the pathogenesis of asthma. 8-Isoprostane is a prostaglandin (PG)-F2-like compound belonging to the F2 isoprostane class that is produced in vivo by the free radical-catalyzed peroxidation of arachidonic acid. 8-Isoprostane is a biomarker of oxidative stress, and its concentration is increased in the bronchoalveolar lavage fluid of patients with interstitial lung diseases. We measured 8-isoprostane concentrations in exhaled breath condensate in healthy subjects and in patients with mild (steroid naive, n = 12), moderate (inhaled steroid treatment, n = 17), and severe asthma (oral steroid treatment, n = 15). We also measured exhaled carbon monoxide (CO) and nitric oxide (NO), which may also reflect oxidative stress in the airways. 8-Isoprostane was detectable in breath condensate of normal subjects (15.8 +/- 1.6 pg/ml), and was increased in the breath condensate of patients with mild (33.7 +/- 2.8, p < 0.001), moderate (38.3 +/- 3.7 pg/ml, p < 0. 001), and severe asthma (48.9 +/- 5.0 pg/ml, p < 0.001). There was a positive correlation (r = 0.68, p < 0.05) of 8-isoprostane with NO, but not with CO, in the exhaled air of patients with mild asthma, but not in that of patients with moderate or severe asthma. There was no correlation between 8-isoprostane and lung function tests in any group of patients. Our study shows that oxidative stress is increased in asthmatic subjects as reflected by 8-isoprostane concentrations in breath condensate.     

8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may compromise oxidative balance. Oxidative stress is increased in the blood and in the airways of OSA patients. DESIGN: The aim of this study was to investigate whether oxidative stress is determined by nocturnal apneas and could be reduced by CPAP therapy, and whether there is a relation between local and systemic oxidative stress in these patients. PATIENTS AND METHODS: Eighteen patients with OSA (13 men; mean [+/- SD] age, 48 +/- 3 years) and 12 healthy age-matched and weight-matched subjects (8 men; mean age, 46 +/- 7 years) were recruited. 8-Isoprostane was measured in exhaled breath condensate and blood by a specific enzyme immunoassay. Measurements and results: Higher concentrations of 8-isoprostane were found in the morning exhaled condensate (9.5 +/- 1.9 pg/mL) and plasma (9.7 +/- 1.5 pg/mL) of OSA patients compared to healthy obese subjects (6.7 +/- 0.2 and 7.1 +/- 0.3 pg/mL, respectively; p < 0.0001). Elevated mean concentrations of exhaled 8-isoprostane were observed in the OSA patients at 8:00 AM (9.5 +/- 1.9 pg/mL) but not at 8:00 PM (7.6 +/- 0.8 pg/mL; p < 0.0005), and a significant reduction was seen after continuous positive airway pressure (CPAP) therapy (7.7 +/- 0.9 pg/mL; before treatment, 9.6 +/- 1.7 pg/mL; p < 0.005). A positive correlation was found between morning exhaled 8-isoprostane levels and the apnea-hypopnea index (r = 0.8; p < 0.0001), and 8-isoprostane levels and neck circumference (r = 0.6; p < 0.0001). CONCLUSIONS: These findings suggest that systemic and local oxidative stress are increased in OSA patients, and that they are higher after nocturnal apnea and reduced by CPAP therapy.     

8-Isoprostane, a marker of oxidative stress, is increased in the expired breath condensate of patients with pulmonary sarcoidosis

STUDY OBJECTIVE: 8-Isoprostane is considered an index of oxidative stress. Measurement of 8-isoprostane in the expired breath condensate, a totally noninvasive method, has not been used to explore the level of inflammation in pulmonary sarcoidosis. Therefore, the aim of our study was to measure the levels of 8-isoprostane in the expired breath condensate of patients with sarcoidosis, and to investigate the relation of 8-isoprostane level to disease activity. PATIENTS: We investigated 30 patients with pulmonary sarcoidosis (active disease, n = 14; nonactive disease, n = 16) and 12 healthy subjects as control group. METHODS: 8-Isoprostane was measured in the expired breath condensate of all subjects, and its levels were compared between the control and sarcoidosis groups as well as between the subgroups of patients with active and nonactive disease. In the group with sarcoidosis, 8-isoprostane levels were further correlated with markers that may reflect disease activity, such as serum angiotensin-converting enzyme (sACE) level, serum calcium level, and pulmonary function test results. RESULTS: The concentration of 8-isoprostane was increased in patients with sarcoidosis compared to control subjects (mean, 64.23 pg/mL; 95% confidence interval [CI], 37.00 to 91.46 pg/mL; vs mean, 20.75 pg/mL; 95% CI, 16.06 to 25.44 pg/mL; p = 0.04). The difference was primarily due to the patients with active disease, who had significantly higher levels of 8-isoprostane (mean, 111.4 pg/mL; 95% CI, 62.56 to 160.30 pg/mL; p < 0.001) compared to patients with nonactive disease (mean, 22.94 pg/mL; 95% CI, 15.89 to 29.99 pg/mL) or healthy subjects. 8-Isoprostane levels in patients with nonactive disease did not differ from those in healthy subjects (p > 0.05). In the patients with sarcoidosis, 8-isoprostane levels were positively correlated with sACE level (p < 0.0001, r = 0.69), but was not correlated with serum calcium level or pulmonary function test values. CONCLUSIONS: Our data suggest that 8-isoprostane levels are increased in the expired breath condensate of patients with sarcoidosis and might serve as an index of disease activity.     

Lactoferrin inhibits lipid peroxidation in patients with chronic hepatitis C.

Lactoferrin is a milk protein with inhibitory effect on lipid peroxidation induced by oxidative stress. Oxidative stress plays an important role in the pathogenesis of chronic hepatitis C (CHC). The aim of this study was to evaluate the effect of bovine lactoferrin (bLF) monotherapy on lipid peroxidation, hepatic inflammation and iron metabolism in patients with CHC. Ninety Japanese patients with CHC were randomly assigned to two groups: bLF group (n=47) treated with bLF at a dose of 3.6g/day and a control group (n=43) that remained untreated. Plasma 8-isoprostane levels and clinical laboratory data including iron metabolism parameters were measured. Plasma 8-isoprostatne level was significantly decreased from 8.6+/-3.7 to 6.9+/-2.1pg/ml in the bLF group (P<0.05). Plasma levels of 8-isoprostane did not significantly change in the control group. The decline in plasma 8-isoprostane levels was positively correlated with improvement in the level of ALT in the bLF group. No significant change in serum HCV RNA levels or iron metabolism markers was found after bLF treatment. Therapy with bLF was associated with improvement in lipid peroxidation and ALT levels in CHC. Administration of bLF is a promising therapeutic approach for suppressing oxidative stress in non-responders to antiviral therapy.     

BAL Fluid 8-Isoprostane Concentrations in Eosinophilic Bronchitis and Asthma

Background. Oxidative stress has an important role in the pathophysiology of asthma. But oxidative stress of airway has not been assessed in patients with nonasthmatic eosinophilic bronchitis (EB). 8-epi-prostaglandin F2alpha (8-isoprostane) is a biomarker of oxidative stress. Objectives. We sought to determine whether oxidative stress (measured by 8-isoprostane) occurs in EB and whether 8-isoprostane is associated with airway function in EB and asthma. Methods. We measured 8-isoprostane concentrations in the bronchoalveolar lavage (BAL) fluid from 11 subjects with EB, 10 subjects with asthma, and 9 healthy control subjects. 8-isoprostane was measured by enzyme immunoassays. Results. We found that BAL fluid 8-isoprostane concentrations were raised both in EB and asthma. The median concentrations of 8-isoprostane in BAL fluid were significantly higher in subjects with asthma (12.78 pg/mL) when compared with EB (8.34 pg/mL) and healthy control subjects (5.07 pg/mL). Conclusions. Our study shows that oxidative stress is increased significantly in asthmatic subjects and the degree of oxidative stress in EB subjects is milder than that in asthma, as reflected by 8-isoprostane concentrations in the BAL fluid. The difference in airway function observed in subjects with EB and asthma could be associated with different elevation in 8-isoprostane concentration in the airways.     

Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD)

BACKGROUND: One of the major pathogenic mechanisms for progression of nonalcoholic fatty liver disease (NAFLD) is oxidative stress. Recently, many studies have demonstrated the role of oxidative stress in NAFLD however, studies describing the antioxidant status in these patients are lacking. AIM: To study the levels of oxidative stress and antioxidant status among patients with NAFLD. PATIENTS AND METHODS: It was a prospective study in which 29 patients with NAFLD, 25 diseased controls with chronic viral hepatitis, and 23 healthy controls were enrolled. Apart from standard biochemical parameters, lipid peroxidation products were measured as thiobarbituric acid reactive substances. As measures of antioxidant capacity, superoxide dismutase, vitamin C levels and ferric reducing ability of plasma were measured. RESULTS: Level of thiobarbituric acid reactive substances was significantly higher among NAFLD patients as compared with diseased [4.7 nmol/mL (1.0 to 10.2) vs. 2.4 nmol/mL (0.8 to 10.7); P=0.02] or healthy controls [4.7 nmol/mL (1.0 to 10.2) vs. 1.8 nmol/mL (0.5 to 4.1); P=0.0001]. FRAP was found to be significantly higher in patients with NAFLD as compared with healthy controls [450.3 (197.6 to 733.3) vs. 340.8 (141.6 to 697.5) mumol Fe liberated; P=0.04], even though it was similar between NAFLD and diseased controls. Among NAFLD patients, there was no significant correlation between histological grading or staging and levels of pro and antioxidants. CONCLUSIONS: Products of lipid peroxidation are significantly increased among patients with NAFLD as compared with chronic viral hepatitis or healthy controls. Larger studies and newer markers of oxidative stress are required to clarify the association between oxidative stress and histological severity in NAFLD.     

The relationship between oxidative stress and acid stress in adult patients with mild asthma

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of asthma. Interestingly, a low airway pH and a high concentration of 8-isoprostane, a marker of oxidative stress, has been reported to cause inflammatory airway diseases. However, the relationship between these 2 markers and pulmonary function has not been determined in mild asthma patients. METHODS: pH and 8-isoprostane concentration were measured in exhaled breath condensate (EBC) from patients with mild asthma (n = 44) and healthy subjects (n = 20). The relationship between acid stress (pH) and oxidative stress (8-isoprostane) was then analyzed, along with the relationships between these 2 markers and lung function. RESULTS: The median (interquartile range [IQR]) pH of EBC was significantly lower in asthma patients than in control subjects (7.53 [7.41-7.68] vs 7.70 [7.62-7.74], P < .05), while the median (IQR) 8-isoprostane concentration of EBC was significantly higher in asthma patients than control subjects (16.2 [11.7-19.1] vs 3.5 [2.6-7.9] pg/mL, P < .05). There was no correlation between pH and 8-isoprostane concentration. Furthermore, lung function was not correlated with either pH or 8-isoprostane concentrations in EBC. CONCLUSIONS: Acid stress and oxidative stress assessed by pH and 8-isoprostane concentration, respectively, in EBC did not show parallel changes associated with asthma and were not correlated with lung function in asthma patients. These 2 stress factors may have different roles in the pathogenesis of asthma.     

Increased exhaled 8-isoprostane in childhood asthma

STUDY OBJECTIVE: To quantify lung oxidative stress in asthmatic children by measuring concentrations of 8-isoprostane, a marker of oxidative stress, in exhaled breath condensate (EBC), which is a noninvasive method of sampling airway secretions. Secondary objectives were as follows: (1) to measure levels of exhaled prostaglandin (PG) E(2), since impaired PGE(2) production has been implicated in the pathogenesis of asthma in adults; and (2) to measure levels of fractional exhaled nitric oxide (FeNO), which is a marker of airway inflammation. DESIGN: Single-center, cross-sectional study. PATIENTS: Twelve healthy children, 12 steroid-na?ve asthmatic children, and 30 children in stable condition with mild-to-moderate persistent asthma who were being treated with inhaled corticosteroids (ICSs) [average dose, 300 micro g per day] were studied. INTERVENTIONS: Subjects attended the outpatient clinic on one occasion for the collection of EBC and FeNO measurements. Measurements and results: 8-Isoprostane and PGE(2) concentrations in EBC were measured with specific radioimmunoassays. FeNO was measured online by a chemiluminescence analyzer. 8-Isoprostane was detectable in the EBC of healthy children (mean [+/- SEM], 34.2 +/- 4.5 pg/mL), and its concentrations were increased in both steroid-na?ve asthmatic children (mean, 56.4 +/- 7.7 pg/mL; p < 0.01) and steroid-treated asthmatic children (mean, 47.2 +/- 2.3 pg/mL; p < 0.05). There was no difference in exhaled 8-isoprostane concentrations between the two groups of asthmatic children (p = 0.14). By contrast, exhaled PGE(2) concentrations were similar among the three study groups (p = 0.56). FeNO levels were higher in steroid-na?ve children with asthma (49.2 +/- 9.6 parts per billion [ppb]; p < 0.05) and, to a lesser extent, in steroid-treated asthmatic children (37.8 +/- 6.6 ppb; p < 0.05) compared with healthy children (15.2 +/- 1.7 ppb). CONCLUSIONS: Lung oxidative stress is increased in children who are in stable condition with asthma, as reflected by increased exhaled 8-isoprostane concentrations. This increase seems to be relatively resistant to treatment with ICSs. Decreased PGE(2) lung production is unlikely to play a pathophysiologic role in childhood asthma.     

Changes in lipid metabolism in chronic hepatitis C

AIM: To investigate the relationship between certain biochemical parameters of lipid metabolism in the serum and steatosis in the liver. METHODS: The grade of steatosis (0-3) and histological activity index (HAI, 0-18) in liver biopsy specimens were correlated with serum alanine aminotransferase (ALT), total cholesterol and triglyceride levels in 142 patients with chronic hepatitis C (CH-C), and 28 patients with non-alcoholic fatty liver disease (NAFLD) without hepatitis C virus (HCV) infection. The serum parameters were further correlated with 1 797 age and sex matched control patients without any liver diseases. RESULTS: Steatosis was detected in 90 out of 142 specimens (63%) with CH-C. The ALT levels correlated with the grade of steatosis, both in patients with CH-C and NAFLD (P<0.01). Inserting the score values of steatosis as part of the HAI, correlation with the ALT level (P<0.00001) was found. The triglyceride and cholesterol levels were significantly lower in patients with CH-C (with and without steatosis), compared to the NAFLD group and to the virus-free control groups. CONCLUSION: Our study confirms the importance of liver steatosis in CH-C which correlates with lower lipid levels in the sera. Inclusion of the score of steatosis into HAI, in case of CH-C might reflect the alterations in the liver tissue more precisely, while correlating with the ALT enzyme elevation.     

Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseases

BACKGROUND/AIMS: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. METHODS: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. RESULTS: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. CONCLUSION: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses.     

Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases.

Oxidative stress may play an important role in the progression of simple steatosis to non-alcoholic steatohepatitis (NASH). Oxidative stress is generated through multiple sources, including oxidation of free fatty acids, cytochrome P4502E1, iron overload, and necro-inflammatory cytokines including tumor necrosis factor-alpha. Oxidative stress may trigger damage to cellular membranes and nuclear DNA, which results in lipid peroxidation and oxidative DNA damage, respectively. Here, we present our data on intrahepatic localization and clinico-pathological significance of oxidative stress-induced cellular damage in the patients with non-alcoholic fatty liver diseases (NAFLD). Our subjects were 23 patients with non-alcoholic simple fatty liver, 17 with NASH, and 7 with normal liver (control). Hepatic expression of 4-hydroxy-2'-nonenal (HNE) and 8-hydroxydeoxyguanosine (8-OHdG), as reliable markers of lipid peroxidation and oxidative DNA damage, was in situ detected by using commercially available monoclonal antibodies. While no HNE adducts were observed in control livers, they were frequently detected in NAFLD. In NASH, the localization of the HNE adducts was in the cytoplasm of sinusoidal cells and hepatocytes with a predominance in zone 3. The grade of necro-inflammation as well as the stage of fibrosis significantly correlated with the HNE labeling index. With respect to 8-OHdG, although no 8-OHdG expression was observed in normal liver and only a few in non-alcoholic simple fatty liver, 11 of 17 patients with NASH (65%) exhibited nuclear expression of 8-OHdG in hepatocytes and sinusoidal cells in areas of active inflammation. The 8-OHdG index significantly correlated with the grade of necro-inflammation, but not with the stage of fibrosis. Our observations suggest that oxidative cellular damage occurs frequently in livers with NAFLD and may be associated with some clinico-pathological features of NAFLD including liver fibrosis and possibly, hepatocarcinogenesis.     

Associations of isoprostanes-related oxidative stress with surrogate subclinical indices and angiographic measures of atherosclerosis

OBJECTIVES: Cardiovascular diseases are the most common cause of death in the world. Oxidative stress has been proved to play a role in atherosclerotic diseases and 8-isoprostane is one of the most valid markers of in-vivo oxidative stress. We aimed to investigate the 8-isoprostane levels in relation to surrogate and direct angiographic indexes of atherosclerosis. METHODS: Urinary 8-isoprostane levels were measured and a B-mode carotid ultrasound examination was performed in 100 consecutive patients scheduled for coronary angiography. RESULTS: In patients with angiographic coronary artery disease (CAD) urinary 8-isoprostane levels were significantly (P<0.001) higher than in patients without CAD (68.75+/-5.5 vs. 38.27+/-3.7 pg/ml). Moreover, 8-isoprostane levels of patients with increased carotid intima media thickness (CIMT) were higher (P<0.001) than in patients with normal CIMT values (75.12+/-6.4 vs. 38.72+/-2.7 pg/ml). Moreover log(8-isoprostane) levels were significantly correlated with maximum and mean CIMT values (P<0.001) and across univessel and multivessel CAD groups levels of log(8-isoprostane) showed a significantly (P<0.001) increasing trend. Logistic regression analysis revealed that 8-isoprostane levels were an independent predictor for both intima-media thickening and angiographic CAD. CONCLUSION: These findings indicate that elevated urinary levels of 8-isoprostane are associated with both subclinical atherosclerosis and manifest CAD. The results therefore support the hypothesis that isoprostanes-related oxidative stress is involved in the whole atherosclerotic process.     

8-异前列腺素F2α在损伤性肝脏疾病中的作用与机制

活性氧自由基引发的氧化应激主要通过启动膜脂质过氧化反应改变生物膜的功能,并在一系列细胞因子的共同作用下引起不同程度的肝损害.8-iso-PGF2α是脂质过氧化反应的特异性产物,具有很强的生物学活性,目前被认为是评价氧化应激和脂质过氧化损伤的金指标.文章简述了损伤性肝脏疾病与脂质过氧化的关系,并提出以8-iso-PGF2α作为肝脏疾病过氧化损伤程度的敏感指标,初步探讨了其在肝脏疾病中的应用前景.     

Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airways obstruction during sleep that result in episodes of hypoxia. An increase of systemic biomarkers of inflammation and oxidative stress has been found in patients with OSA and obesity. DESIGN: The aim of this study was to measure the levels of markers of inflammation (interleukin [IL]-6) and oxidative stress (8-isoprostane) in the exhaled breath condensate of OSA and obese patients. PATIENTS AND METHODS: Eighteen OSA patients (13 men; mean [+/- SEM] age, 44 +/- 7 years), 10 obese subjects (4 men; mean age, 39 +/- 8 years), and 15 healthy age-matched subjects (8 men; mean age, 42 +/- 4 years) were recruited. IL-6 and 8-isoprostane were measured in exhaled breath condensate by a specific enzyme immunoassay kit. Measurements and results: Higher concentrations of IL-6 were found in OSA patients (8.7 +/- 0.3 pg/mL) than in healthy control subjects (1.6 +/- 0.1 pg/mL; p < 0.0001). Obese subjects also had higher levels than healthy control subjects, but lower levels than OSA patients (2.1 +/- 0.2 pg/mL, p < 0.05 and p < 0.0001 respectively). Furthermore, 8-isoprostane levels were found to be higher in OSA patients (7.4 +/- 0.7 pg/mL) than in obese subjects (5 +/- 0.3 pg/mL; p = 0.4) and healthy subjects (4.5 +/- 0.5 pg/mL; p < 0.005). We found a positive correlation between these two markers and neck circumference and apnea/hypopnea index. CONCLUSIONS: These findings suggest that inflammation and oxidative stress are characteristic in the airways of OSA patients but not in obese subjects, and that their levels depend on the severity of the OSA. The measurement of IL-6 and 8-isoprostane levels may prove to be useful in screening and monitoring obese patients who have a high risk of developing OSA.     

Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C

OBJECTIVES: Hepatic iron deposition has been reported in chronic hepatitis C (CH-C), and iron-induced lipid peroxidation may be involved in the pathogenesis of CH-C. The aims of the present study were: 1) to determine whether patients with CH-C have evidence of enhanced hepatic lipid peroxidation and to evaluate its relation to iron status, compared with that in patients with chronic hepatitis B (CH-B); and 2) to assess the effect of interferon (IFN) therapy on hepatic iron and lipid peroxidation. METHODS: In the liver biopsies of 40 patients with CH-C and 26 patients with CH-B, immunohistochemical detection of 4-hydroxy-2-nonenal (HNE)-protein adducts for evaluation of lipid peroxidation was performed, and hepatic iron status was biochemically and histologically assessed. In 16 CH-C patients with normal serum transaminases and undetectable serum HCV-RNA >6 months after the end of IFN treatment (responders) and in 11 nonresponders, hepatic HNE-protein adducts and siderosis were evaluated in pre- and posttreatment liver biopsies. RESULTS: Hepatocytic HNE-protein adducts and iron deposits were more abundant in the patients with CH-C than in those with CH-B. No correlation was found between the levels of hepatocytic HNE-protein adducts and hepatic iron status in either of the two groups. In the responders to IFN treatment for CH-C, hepatocytic HNE-protein adducts disappeared or attenuated with improvement of hepatic siderosis after the treatment, whereas IFN treatment did not improve hepatocytic expression of HNE-protein adducts and hepatic siderosis in the nonresponders. CONCLUSIONS: Patients with CH-C have evidence of enhanced hepatic iron accumulation and lipid peroxidation compared to those with CH-B. In CH-C, hepatic siderosis and lipid peroxidation are improved with successful IFN treatment. These results suggest that hepatic lipid peroxidation and iron may potentially play contributory roles in the pathogenesis of CH-C.     

8-Isoprostane as a marker of oxidative stress in nonsymptomatic cigarette smokers and COPD.

8-Isoprostane is a potential in vivo marker for oxidant burden, but its usefulness in induced sputum of smokers and chronic obstructive pulmonary disease (COPD) has not been investigated. The current study investigated 58 subjects comprising 11 never-smokers, 11 ex-smokers, 13 healthy current smokers and 23 COPD with stage 0-III disease (according to the Global Initiative for Chronic Obstructive Lung Disease criteria). 8-Isoprostane was determined from induced sputum by enzyme immunoassay. Sputum 8-isoprostane levels were similar in the never-smokers and ex-smokers, but were elevated in the healthy smokers compared with nonsmokers, and in those with stage I-III COPD. Sputum 8-isoprostane levels could not differentiate nonsymptomatic smokers from those with Stage 0 COPD. There was a correlation between sputum 8-isoprostane level and lung function parameters (forced expiratory volume in one second/forced vital capacity and sputum neutrophils. In conclusion, sputum 8-isoprostane levels correlate with the severity of chronic obstructive pulmonary disease. However, they do not appear to differentiate healthy smokers from those who are at risk of developing chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease stage 0).     

Supplemental Vitamin D and Calcium in the Management of African Americans With Heart Failure Having Hypovitaminosis D

IntroductionA dyshomeostasis of macro- and micronutrients, including vitamin D and oxidative stress, are common pathophysiologic features in patients with congestive heart failure (CHF). In African Americans (AA) with CHF, reductions in plasma 25(OH)D are of moderate-to- marked severity (< 20 ng/mL) and may be accompanied by ionized hypocalcemia with compensatory increases in serum parathyroid hormone (PTH). The management of hypovitaminosis D in AA with CHF has not been established.MethodsHerein, a 14-week regimen: an initial 8 weeks of oral ergocalciferol (50,000 IU once weekly); followed by a 6-week maintenance phase of cholecalciferol (1400 IU daily); and a CaCO₃ (1000 mg daily) supplement given throughout was designed and tested. Fourteen AA patients having a dilated (idiopathic) cardiomyopathy with reduced ejection fraction (EF, < 35%) were enrolled: all completed the initial 8-week course; and 12 complied with the full 14 weeks. At baseline, 8 and/or 14 weeks, serum 25(OH)D and PTH; serum 8-isoprostane, a biomarker of lipid peroxidation, and echocardiographic EF were monitored.ResultsReduced 25(OH)D at entry (14.4 ± 1.3 ng/mL) was improved (P < 0.05) in all patients at 8 weeks (30.7 ± 3.2 ng/mL) and sustained (P < 0.05) at 14 weeks (30.9 ± 2.8 ng/mL). Serum PTH, abnormally increased in 5 patients at baseline (104.8 ± 8.2 pg/mL), was reduced at 8 and 14 weeks (74.4 ± 18.3 and 73.8 ± 13.0 pg/mL, respectively). Plasma 8-isoprostane at entry (136.1 ± 8.8 pg/mL) was reduced at 14 weeks (117.8 ± 7.8 pg/mL; P < 0.05), whereas baseline EF (24.3 ± 1.7%) was improved (31.3 ± 4.3%; P < 0.05).ConclusionsThus, the 14-week course of supplemental vitamin D and CaCO₃ led to healthy 25(OH)D levels in AA with heart failure having vitamin D deficiency of moderate-to-marked severity. Albeit a small patient population, the findings suggest that this regimen may attenuate the accompanying secondary hyperparathyroidism and oxidative stress and improve ventricular function.     

Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin-eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions.     

Oxidative stress in chronic hepatitis C: not just a feature of late stage disease

BACKGROUND/AIMS: Chronic hepatitis C infection is a major world-wide problem, frequently progressing to cirrhosis, liver failure or hepatoma. The pathological mechanisms of disease progression are unclear but oxidant stress may play a role.METHODS: Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis and liver function were measured in blood or urine from 42 chronic hepatitis C patients. Fibrosis was graded histologically in a subgroup of 33 patients.RESULTS: The lipid peroxidation marker 8-isoprostane and the ratio of oxidized to reduced glutathione were significantly elevated (P<0.001, P=0.006). The antioxidants glutathione, selenium and vitamins A, C and E were significantly decreased (all P<0.001) compared to age and sex matched controls. Abnormal values were more marked in cirrhotics, but significant changes were also observed in the non-cirrhotic group. The fibrosis score correlated positively with urinary 8-isoprostane and type III procollagen peptide and negatively with vitamin A.CONCLUSIONS: Oxidant stress, as reflected in blood and urine by a wide range of pro- and antioxidant markers, is a significant feature of hepatitis C infection. Although more severe in the cirrhotic group, there was clear evidence of oxidant stress in non-cirrhotic patients. Antioxidant therapy may therefore have a role in slowing disease progression to cirrhosis.     

8-iso-prostaglandin F2alpha as a useful clinical biomarker of oxidative stress in ESRD patients

BACKGROUND/AIMS: Chronic renal failure is associated with elevated indices of oxidative stress. We tested the hypothesis that the in vivo formation of the F(2)-isoprostane (8-iso-prostaglandin PGF(2alpha)), a bioactive product of arachidonic acid peroxidation, is enhanced in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). METHODS: Plasma samples were obtained from 35 HD patients, 30 CAPD patients and 30 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF(2alpha). RESULTS: Plasma 8-iso-PGF(2alpha) levels were significantly higher (p < 0.001) in HD and CAPD patients (346.3 +/- 132.4 pg/ml; range 49.8-870) than in age-matched control subjects (150.9 +/- 61.6 pg/ml; range 33.5-235). In addition, we also found that 8-iso-PGF(2alpha) concentration was significantly (p = 0.007) higher in HD patients (389.8 +/- 148.3 pg/ml) than in CAPD patients (254.3 +/- 76.6 pg/ml). Plasma 8-iso-PGF(2alpha) concentration was linearly correlated with serum haptoglobin, C-reactive protein (CRP) and plasma MDA (r = 0.58, p = 0.003; r = 0.29, p < 0.05 and r = 0.38, p < 0.05 respectively). On the other hand, plasma 8-iso-PGF(2alpha) levels were inversely associated with serum albumin and total cholesterol (r = -0.31 and r = -0.28, respectively; p < 0.05). CONCLUSIONS: We conclude that ESRD on both HD and CAPD is associated with increased formation of F(2)-isoprostanes, a correlate of enhanced lipid peroxidation. We also found that plasma 8-iso-PGF(2alpha) was casually related to some acute phase reactant proteins such as serum CRP, albumin and haptoglobin. This may provide an important biochemical link between lipid peroxidation, inflammation and accelerated atherosclerosis in the uremic milieu.