8-hydroxy-2--deoxyguanosine and Pulmonary-Disease--Chronic-Obstructive

Oxidative stress is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is recognized as a biomarker of oxidative stress and is implicated in several pulmonary diseases. Nonetheless, the role of 8-OHdG remains unclear in COPD patients. This research aimed to evaluate the correlations between serum 8-OHdG on admission and the severity and prognosis of hospitalized COPD patients with acute exacerbation.. A total of 150 COPD hospitalized patients and 150 healthy individuals were recruited. Serum 8-OHdG was measured by ELISA and the length of hospital stay was calculated. The number of acute exacerbations of COPD was tracked within 1 year after this hospitalization.. The levels of serum 8-OHdG were elevated in COPD patients compared with the control group. Serum 8-OHdG was gradually elevated with decreased pulmonary function in COPD patients. Furthermore, Pearson linear association found that the levels of serum 8-OHdG were inversely correlated with pulmonary function and positively correlated with inflammatory cytokines in COPD patients. In addition, logistic regression analysis revealed that serum 8-OHdG elevation was a risk factor for pulmonary function decline in COPD patients. The length of hospital stay was tracked at this time. Higher serum 8-OHdG on admission increased the length of hospital stay among COPD patients.. Serum 8-OHdG on admission is positively correlated with the severity and adverse prognosis among COPD patients, suggesting that 8-OHdG may be involved in the pathogenesis of COPD. Serum 8-OHdG may be a biomarker to predict the progression of COPD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Disease Progression; Humans; Lung; Oxidative Stress; Prognosis; Pulmonary Disease, Chronic Obstructive

Polycyclic aromatic hydrocarbons (PAHs) are toxic airborne pollutants and may cause adverse effects at high level of oxidative stress. Here we hypothesized that individuals with impaired lung function are susceptible to PAHs associated oxidative damage. Hence, we carried out a panel study and conducted four follow-up visits on 40 chronic obstructive pulmonary disease (COPD) patients and 75 healthy controls. Hydroxylated PAHs (OH-PAHs) and malonaldehyde (MDA) were measured in urine as exposure and oxidative stress markers, respectively, which showed significant association in all participants. Quantitatively, a 1-fold increase in OH-PAHs was associated with a 4.1-15.1% elevation of MDA. The association between OH-PAHs and MDA levels became stronger in participants with impaired lung function. For 1% decrease of FEV1/FVC, the increase of MDA associated with a 1-fold increase in OH-PAHs was up to 0.49%, suggesting an increased susceptibility to PAH-induced oxidative damage in individuals with worse lung function. This study observed that impaired lung function modified the association between PAH exposure and oxidative damage, which might accelerate the aggravation of COPD, and therefore highlighted the necessity of protection measures to decrease the additional adverse effects of air pollution exposure. CAPSULE: Individuals with worse lung function may be more susceptible to PAH-induced lipid peroxidation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Environmental Pollutants; Humans; Lipid Peroxidation; Oxidative Stress; Polycyclic Aromatic Hydrocarbons; Pulmonary Disease, Chronic Obstructive

A reliable and fast liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous determination of three oxidized nucleic acid damage products in urine, 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). We applied this method to assess the effect of various urine workup procedures on the urinary concentrations of the oxidized nucleic acid products. Our results showed that frozen urine samples must be warmed (i.e., to 37 °C) to re-dissolve any precipitates prior to analysis. We showed that common workup procedures, such as thawing at room temperature or dilution with deionized water, are not capable of releasing fully the oxidized nucleic acid products from the precipitates, and result in significant underestimation (up to ~ 100% for 8-oxoGua, ~ 86% for both 8-oxodGuo and 8-oxoGuo). With this method, we further assessed and compared the ability of the three oxidized nucleic acid products, as well as malondialdehyde (MDA, a product of lipid peroxidation), to biomonitor oxidative stress in vivo. We measured a total of 315 urine samples from subjects with burdens of oxidative stress from low to high, including healthy subjects, patients with chronic obstructive pulmonary disease (COPD), and patients on mechanical ventilation (MV). The results showed that both the MV and COPD patients had significantly higher urinary levels of 8-oxoGua, 8-oxodGuo, and 8-oxoGuo (P < 0.001), but lower MDA levels, compared to healthy controls. Receiver operating characteristic curve analysis revealed that urinary 8-oxoGuo is the most sensitive biomarker for oxidative stress with area under the curve (AUC) of 0.91, followed by 8-oxodGuo (AUC: 0.80) and 8-oxoGua (AUC: 0.76). Interestingly, MDA with AUC of 0.34 failed to discriminate the patients from healthy controls. Emerging evidence suggests a potential clinical utility for the measurement of urinary 8-oxoGuo, and to a lesser extent 8-oxodGuo, which is strongly supported by our findings.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Chromatography, Liquid; Deoxyguanosine; Female; Guanine; Guanosine; Humans; Male; Metabolome; Metabolomics; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Reactive Oxygen Species; ROC Curve; Tandem Mass Spectrometry; Temperature

8-Hydroxy-2’-deoxyguanosine (8-OHdG) is a biomarker of oxidative stress and has been implicated in many diseases. The aim of this study was to investigate the clinical value of plasma 8-OHdG level in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).. A total of 154 subjects were enrolled in this study, including 20 healthy volunteers, 24 COPD patients in the stable phase, and 110 AECOPD patients. Peripheral blood samples, demographic information, and clinical characteristics were collected from all subjects at the time of being recruited into the study. Plasma 8-OHdG level was detected by enzyme-linked immunosorbent a ss ay.. 8-OHdG was increased in patients with AECOPD compared to healthy subjects and patients with stable COPD, especially in smokers. It also increased with the GOLD stage, mMRC grade, CAT score, and group level of combined COPD assessment. Additionally, further analysis revealed that 8-OHdG was negatively correlated with FEV1, FEV1% predicted, and FEV1/FVC and positively correlated with C-reactive protein, procalcitonin, and neutrophil CD64.. 8-OHdG is associated with spirometric severity, symptomatic severity, exacerbation risk, and inflammatory biomarkers in AECOPD patients, suggesting it as a promising biomarker for reflecting disease severity and guiding the choice of optimal therapeutic decision.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Case-Control Studies; Deoxyguanosine; Female; Humans; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Risk; Smoking

Angiotensin II (ANG II) might play an important role in the co-effects of cold stress and fine particulate matter (PM

Topics: 8-Hydroxy-2'-Deoxyguanosine; Angiotensin II Type 1 Receptor Blockers; Animals; Cold Temperature; Deoxyguanosine; Disease Models, Animal; Gene Expression Regulation; Heme Oxygenase-1; Humans; Male; Malondialdehyde; NF-kappa B; Particulate Matter; Pulmonary Disease, Chronic Obstructive; Rats; Tumor Necrosis Factor-alpha; Valsartan

To investigate the effects of exposure to ambient particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) on systemic oxidative stress biomarkers in chronic obstructive pulmonary disease (COPD) patients.. A panel of forty-five diagnosed and stable COPD patients, whose residences were within 5 kilometers from Peking University Health Science Center (PKUHSC), were recruited and followed up twice between November 2014 and May 2015. The lung function index percentage of forced expiratory volume in 1 second (FEV. In our COPD-patient panel, the associations between ultrafine particles (UFP) and PAHs and urinary MDA were statistically significant at lag2 (P<0.05). For an interquartile range (IQR) increase in UFP and PAHs, respective increases of 28% (95%CI: 4%-57%) and 36% (95%CI: 4%-77%) in urinary MDA were observed, and the effects became stronger after adjusting for the concentration of black carbon (BC). The COPD patients were divided into 2 groups stratified by FEV. Our results suggested that exposure to air pollutants, especially UFP and PAHs, was responsible for exacerbation of systemic oxidative stress in COPD patients. Most air pollutants had stronger effects of systemic oxidative stress in mild to moderate COPD patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Air Pollutants; Air Pollution; Biomarkers; Deoxyguanosine; Humans; Linear Models; Malondialdehyde; Oxidative Stress; Particulate Matter; Polycyclic Aromatic Hydrocarbons; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Soot

The genetic and non-genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are still poorly understood. We investigated the potential role of genetic variants of xenobiotic-metabolising enzymes (glutathione-S-transferase M1, GSTM1; glutathione-S-transferase T1, GSTT1; microsomal epoxide hydrolase, mEH), oxidative stress (assessed by urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine, 8-oxodG/creatinine), sex, ageing and smoking habits on susceptibility to development of COPD and its severity in Serbian population. The investigated population consisted of 153 healthy subjects (85 males and 68 females) and 71 patients with COPD (33 males and 38 females). Detection of GSTM1*null, GSTT1*null, mEH Tyr113His and mEH His139Arg gene variants was performed by PCR/RFLP method. Urinary 8-oxodG was determined using HPLC-MS/MS, and expressed as 8-oxodG/creatinine. We revealed that increased urinary 8-oxodG/creatinine and leucocytosis are the strongest independent predictors for COPD development. Increased level of oxidative stress increased the risk for COPD in males [odds ratio (OR), 95% confidence interval (CI): 8.42, 2.26-31.28], more than in females (OR, 95% CI: 3.60, 1.37-9.45). Additionally, independent predictors for COPD were ageing in males (OR, 95% CI: 1.29, 1.12-1.48), while in females they were at least one GSTM1 or GSTT1 gene deletion in combination (OR, 95% CI: 23.67, 2.62-213.46), and increased cumulative cigarette consumption (OR, 95% CI: 1.09, 1.01-1.16). Severity of COPD was associated with the combined effect of low mEH activity phenotype, high level of oxidative stress and heavy smoking. In conclusion, early identification of GSTM1*null or GSTT1*null genotypes in females, low mEH activity phenotype in heavy smokers and monitoring of oxidative stress level can be useful diagnostic and prognostic biomarkers.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Age Factors; Aged; Alleles; Base Sequence; Biomarkers; Body Mass Index; Case-Control Studies; Creatinine; Deoxyguanosine; Epoxide Hydrolases; Female; Genetic Predisposition to Disease; Genotype; Glutathione Transferase; Humans; Male; Middle Aged; Oxidative Stress; Phenotype; Pulmonary Disease, Chronic Obstructive; Risk Factors; Sequence Deletion; Serbia; Severity of Illness Index; Sex Factors; Smoking

Oxidative stress has long been recognized to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and aging, initiating oxidative damage of biomolecules. In this study the development of imbalances in the system of lipid peroxidation and increase the level of the marker of oxidative damage to DNA - 8-hydroxy-deoxyguanosine (8-ОНdG) in patients with COPD and healthy individuals. Evaluation of the relationship between the parameters of the system of lipid peroxidation and the level of 8-ОНdG allowed to drill down to different oxidative mechanisms in the pathogenesis of COPD in patients of middle or old age.. Окислительный стресс играет важную роль в патогенезе ХОБЛ и процессах старения, инициируя окислительное повреждение биомолекул. В настоящем исследовании установлено развитие дисбаланса в системе липопероксидации и увеличение уровня маркера окислительного повреждения ДНК — 8-гидрокси-дезоксигуанозина (8-ОНdG) у больных ХОБЛ и с возрастом у здоровых лиц. Оценка взаимоотношений параметров системы липопероксидации и уровня 8-ОНdG позволила детализировать различные окислительные механизмы патогенеза ХОБЛ у больных среднего и пожилого возраста.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Age Factors; Aged; Biomarkers; Deoxyguanosine; DNA Damage; Female; Humans; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Statistics as Topic

Oxidative damage is a major contributing factor to carcinogenesis and obstructive disorders in lungs. Current evidence suggests that the inflammatory processes yield to oxidative mechanisms, which underlie COPD, lung cancer, and obstructive sleep apnea syndrome (OSAS). This study aimed to evaluate the oxidative damage in these diseases by evaluating the oxidative and antioxidant biomarkers.. Malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and coenzyme Q10 levels were evaluated in the blood samples of subjects with COPD, lung cancer, and OSAS by high-pressure liquid chromatography.. A total of 111 participants (35 females, 76 males) with OSAS (n = 29), COPD (n = 26), and lung cancer (n = 28) and healthy controls (n = 28) were included in the study. The malondialdehyde and coenzyme Q10 levels were significantly higher in all 3 diseases when compared with controls (P < .01), whereas 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were only significantly higher than in healthy controls in subjects with lung cancer (P = .005). The highest levels of malondialdehyde and coenzyme Q10 were determined in subjects with OSAS and lung cancer, respectively. The highest 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were also observed in subjects with lung cancer, but the differences of this biomarker with other diagnoses were not statistically significant (P = .56).. Oxidative damage was observed in all 3 diagnoses, and, as a response to oxidative stress, antioxidant mechanisms were also active in these diseases. Malondialdehyde and 8-oxo-7,8-dihydro-2'-deoxyguanosine were found to be efficiently usable in the evaluation of oxidative damage in chronic respiratory diseases. (ClinicalTrials.gov registration NCT02406053.).

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Biomarkers; Case-Control Studies; Deoxyguanosine; Female; Humans; Lung Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Ubiquinone

Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease and is an important cause of morbidity worldwide. The aim of this study was to evaluate whether pulmonary rehabilitation (PR) improves the oxidant/antioxidant imbalance, exercise capacity and health-related quality of life (HRQL) in patients with different stages of COPD. Eighteen stable COPD patients participated in 8-week PR; the exercise intensity was set at 70% of the VO2 peak. Subjects were divided into 2 groups: moderate to severe (stages II/III: n = 12) and very severe COPD with FEV1 < 30% predicted (stage IV: n = 6). In patients at stages II/III, PR improved exercise capacity (6-minute walking test: 431.2 ± 26.6 vs. 489.1 ± 26.5 m, P < 0.01 and shuttle walking test: 329.2 ± 41.4 vs. 378.2 ± 41.5 m, P < 0.01) and HRQL, whereas no significant change was observed in erythrocyte lipid peroxidation and urinary 8-hydroxydeoxyguanosine, a marker for DNA damage. In contrast, PR for stage IV patients did not improve exercise capacity and HRQL, but significantly increased urinary 8-hydroxydeoxyguanosine (14.5 ± 1.7 vs. 24.3 ± 2.6 ng/mg Cr, P < 0.05). In both groups, erythrocyte antioxidants (superoxide dismutase, glutathione peroxidase, and catalase) did not change significantly after PR. Thus, urinary 8-hydroxydeoxyguanosine is a useful indicator for the PR-induced oxidative stress in COPD patients. In conclusion, appropriate exercise program in COPD patients can improve exercise capacity and HRQL without further increase of oxidative stress. However, PR for very severe COPD patients enhanced exercise-induced oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Biomarkers; Bronchodilator Agents; Deoxyguanosine; Erythrocytes; Exercise Therapy; Humans; Japan; Male; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Quality of Life; Respiratory Function Tests; Statistics, Nonparametric

Oxidative stress has long been recognized to play a role in chronic obstructive pulmonary disease (COPD); however, approaches for assessing oxidative stress are lacking. The objective of this study was to address the feasibility of measuring 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-OHdG) formation and human 8-oxoguanine DNA glycosylase (hOGG1) induction in peripheral blood mononuclear cell (PBMC) to assess oxidative deoxyribonucleic acid (DNA) damage in the lung of smoking COPD patients.. PBMC were obtained from 412 participants including 129 smokers with COPD, 143 healthy smokers and 140 healthy non-smokers. Lung tissue specimens and PBMC were obtained from smoker COPD (n = 12), healthy smokers (n = 12) and healthy non-smokers (n = 10). 8-OHdG and hOGG1 were detected, and correlation analysis was conducted for assessing the feasibility.. Oxidative DNA damage (8-OHdG formation) along with impaired induction of hOGG1 expression in the lung was a prominent feature for smokers COPD patients. PBMC originated from smokers COPD patients also displayed similar features to that of lung tissues. Correlation analysis suggests that PBMC could be used as a surrogate for oxidative DNA damage in lung of smokers COPD patients. Indeed, 8-OHdG levels in PBMC DNA were negatively correlated with lung function, while hOGG1 induction in PBMC was associated with improved lung function in smokers COPD patients.. COPD patients manifest oxidative DNA damage of 8-OHdG along with impaired hOGG1 expression in the lung, whereas 8-OHdG formation and hOGG1 induction in PBMC could be a biomarker of oxidative DNA damage in the lung.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Deoxyguanosine; DNA Damage; DNA Glycosylases; Female; Guanine; Humans; Leukocytes, Mononuclear; Lung; Male; Middle Aged; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Smoking; Statistics as Topic

Chronic exposure to high levels of ozone induces emphysema and chronic inflammation in mice. We determined the recovery from ozone-induced injury and whether an antioxidant, N-acetylcysteine (NAC), could prevent or reverse the lung damage.. Mice were exposed to ozone (2.5 ppm, 3 hours/12 exposures, over 6 weeks) and studied 24 hours (24h) or 6 weeks (6W) later. Nac (100 mg/kg, intraperitoneally) was administered either before each exposure (preventive) or after completion of exposure (therapeutic) for 6 weeks.. After ozone exposure, there was an increase in functional residual capacity, total lung volume, and lung compliance, and a reduction in the ratio of forced expiratory volume at 25 and 50 milliseconds to forced vital capacity (FEV25/FVC, FEV50/FVC). Mean linear intercept (Lm) and airway hyperresponsiveness (AHR) to acetylcholine increased, and remained unchanged at 6W after cessation of exposure. Preventive NAC reduced the number of BAL macrophages and airway smooth muscle (ASM) mass. Therapeutic NAC reversed AHR, and reduced ASM mass and apoptotic cells.. Emphysema and lung function changes were irreversible up to 6W after cessation of ozone exposure, and were not reversed by NAC. The beneficial effects of therapeutic NAC may be restricted to the ASM.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcysteine; Animals; Apoptosis; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Deoxyguanosine; Disease Models, Animal; Emphysema; Expectorants; Gene Expression; Lung; Malondialdehyde; Mice; Ozone; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

In this study, we investigated whether DNA double-strand breaks (DSBs) contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). We immunofluorescence-stained lung tissue samples obtained from COPD patients, asymptomatic smokers and nonsmokers for markers of DSBs. The numbers of DSB foci (phosphorylated histone 2AX (γH2AX), phosphorylated ATM (ataxia telangiectasia mutated) substrate and phosphorylated p53-binding protein-1 foci) per cell in alveolar type I and II cells and endothelial cells were higher in the COPD patients than in the asymptomatic smokers and nonsmokers. The lung tissue in which type II cells contained higher numbers of γH2AX foci per cell had higher percentages of type II cells that expressed p16(INK4a) (p16), phosphorylated nuclear factor (NF)-κB and interleukin (IL)-6, and of alveolar wall cells that expressed active caspase-3. The type II cells that contained higher numbers of γH2AX foci per cell had higher rates of expression of p16, phosphorylated NF-κB, and IL-6. Half of the alveolar wall cells that expressed active-caspase-3 contained γH2AX foci. Type II cells that stained positive for 8-hydroxy-2-deoxyguanosine contained a higher number of γH2AX foci per cell than the type II cells that stained negative. In conclusion, DSBs, at least in part caused by oxidative stress, appear to contribute to the pathogenesis of COPD by inducing apoptosis, cell senescence and pro-inflammatory responses.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Caspase 3; Cell Cycle Proteins; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p16; Deoxyguanosine; DNA Breaks, Double-Stranded; DNA-Binding Proteins; Female; Histones; Humans; Interleukin-6; Male; Middle Aged; NF-kappa B; Oxidative Stress; Protein Serine-Threonine Kinases; Pulmonary Alveoli; Pulmonary Disease, Chronic Obstructive; Smoking; Tumor Suppressor Proteins

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that mediates proinflammatory gene expression. NF-kappaB is activated when its inhibitor, IkappaBalpha, is phosphorylated and degraded.. The aims of this study were to compare the number of phosphorylated IkappaBalpha-immunopositive airway epithelial cells (AECs) in the peripheral airways of patients with COPD, asymptomatic smokers and asymptomatic nonsmokers.. We examined lung tissues obtained from 10 smokers with COPD, 7 asymptomatic smokers and 10 asymptomatic nonsmokers. Paraffin-embedded sections and immunohistochemical techniques were used to assess the number of phosphorylated IkappaBalpha-positive AECs as well as the numbers of tumor necrosis factor (TNF)alpha-positive, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive and 4-hydroxy-2-nonenal (4-HNE)-positive AECs in the peripheral airway specimens.. The percentages of phosphorylated IkappaBalpha-positive AECs and TNFalpha-positive AECs out of the total number of AECs were significantly higher in patients with COPD than in asymptomatic nonsmokers (p < 0.05). The percentage of phosphorylated IkappaBalpha-positive AECs was positively correlated with the percentage of TNFalpha-positive AECs (r = 0.82, p < 0.01), but not with the percentage of 8-OHdG-positive AECs or the percentage of 4-HNE-positive AECs.. The activation of NF-kappaB, which was evaluated by measuring the level of phosphorylated IkappaBalpha, was enhanced in the peripheral airway epithelia of the COPD patients in this study. The activation of NF-kappaB in the peripheral airway epithelium is associated with an elevated level of TNFalpha and seems to occur through a mechanism independent of oxidative stress.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aldehydes; Deoxyguanosine; Epithelial Cells; Female; Forced Expiratory Volume; Humans; I-kappa B Proteins; Immunoenzyme Techniques; Male; Middle Aged; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Smoking; Tumor Necrosis Factor-alpha

Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has antioxidative, antiapoptotic, and antiinflammatory activities. We examined whether HO-1 might be involved in silicosis.. To investigate whether HO-1 can reduce silicosis in mice and humans.. Silicosis was studied using a murine model, and in 46 male patients. Serum HO-1 and 8-hydroxydeoxyguanosine (a marker of oxidative stress) were measured by enzyme-linked immunosorbent assay. Levels of HO-1 were measured by immunohistochemistry and immunoblotting.. Serum HO-1 levels were significantly elevated in patients with silicosis compared with age-matched control subjects or patients with chronic obstructive pulmonary disease. Serum HO-1 levels also correlated inversely with serum 8-hydroxydeoxyguanosine levels and positively with vital capacity and forced expiratory volume in one second in patients with silicosis. HO-1 was present in the lungs of humans and mice with silicosis, especially at sites of silica particle deposition. In mice, silica exposure was associated with acute leukocyte infiltration, leading to development of silicotic lung lesions. The inflammation was suppressed by treatment with hemin, an inducer of HO-1, and enhanced by zinc protoporphyrin, an inhibitor of HO-1.. Pulmonary HO-1 expression is increased in silicosis. HO-1 suppresses reactive oxygen species activity, and subsequent pathologic changes, thereby attenuating disease progression.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Animals; Biomarkers; Chronic Disease; Deoxyguanosine; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Heme Oxygenase-1; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Middle Aged; Oxidative Stress; Prognosis; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Silicosis

The purpose of this study was to investigate whether patients with COPD are under oxidative stress and to elucidate the relationship between the level of oxidative stress and antioxidant vitamins.. Nineteen male patients with COPD and 13 age- matched male control subjects were studied. Urinary 8-hydroxydeoxyguanosine (8-OHdG) concentrations were determined using an enzyme-linked immunosorbent assay kit and corrected for creatinine concentrations. Serum levels of vitamin C, alpha-tocopherol, and beta-carotene were determined by high performance liquid chromatography.. The median (interquartile range) 8-OHdG excretion was 8.1 ng/mg (5.3-10.9 ng/mg) in control subjects and 12.2 ng/mg (9.8-15.5 ng/mg) in COPD patients (P < 0.01). Urinary 8-OHdG levels were significantly elevated in ex-smokers in the COPD group compared with ex-smokers in the control group. Urinary 8-OHdG level was negatively correlated with FVC (r = -0.42, P = 0.016), FEV1 (r = -0.49, P = 0.0048), and oxygen tension in arterial blood (r = -0.41, P = 0.0005). No significant differences in antioxidant levels were demonstrated between the two groups. There were no significant correlations between urinary 8-OHdG excretion and the serum concentrations of antioxidant vitamins.. The burden of oxidative stress was observed to increase in COPD patients as judged by urinary 8-OHdG. A depletion of antioxidant vitamins in serum was not essential for this phenomenon. Elevated urinary 8-OHdG level may not be attributable to smoking status or to antioxidant vitamins in COPD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Case-Control Studies; Deoxyguanosine; Humans; Male; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Statistics, Nonparametric