Inhaled glucocorticosteroids decrease hydrogen peroxide level in expired air condensate in asthmatic patients

AbstractH2O2is elevated in the exhaled air condensate in several inflammatory disorders of the lung, including bronchial asthma, and thus may reflect inflammatory processes in the airways. Exhaled H2O2may be used to guide the anti-inflammatory treatment of patients with asthma. Therefore in this study we analysed the effect of inhaled glucocorticosteroid beclomethasone for 4 weeks on H2O2level in the exhaled air condensate.Seventeen asthmatics and 10 healthy subjects were included to the study. Eleven patients were given inhaled beclomethasone and six were given placebo (3M Health Care). In all patients pulmonary function tests were performed. H2O2in the expired air condensate was measured spectrofluorimetically (homovanillic acid method).Inhaled beclomethasone significantly decreased H2O2in the expired air condensate in the active-treatment group, with a fall from baseline on day 1 which remained on day 43 (follow-up) (P<0·05). Exhaled H2O2in the active-treatment group was significantly lower than that in placebo group (P<0·05). A negative correlation between H2O2and forced expiratory volume in 1 sec (FEV1) on day 29 was observed.The decrease in exhaled H2O2in the active-treatment group was accompanied by an improvement in pulmonary function tests results.Inhaled glucocorticoids reduce the level of H2O2in the expired air condensate of asthmatic patients over a 4-week period and this may reflect their anti-inflammatory activity in lung diseases

Differential effect of cigarette smoking on hydrogen peroxide and thiobarbituric acid reactive substances exhaled in patients with community acquired pneumonia

Background. This study was designed to investigate the effect of cigarette smoking on hydrogen peroxide (H2O2) and thiobarbituric reactive substances (TBARs) concentrations in exhaled breath condensate (EBC) in patients with community acquired pneumonia (CAP). Methods. H2O2 and TBARs concentrations in EBC were determined with spectrofluorimetrical assays. Results. Non-smoking CAP patients (n=24) exhaled 1.4, 1.8 and 1.7 times more H2O2 than the smoking patients with CAP (n=19) as assessed one (0.73±0.32 μM v. 0.51±0.36 μM), three (0.84±0.31 μM v. 0.47±0.24 μM) and five (0.66±0.28 μM v. 0.40±0.35 μM) days after admission (p<0.05 in each case). Over 10 days of hospital treatment, mean level of exhaled H2O2 0.45±0.22 μM in CAP patients with smoking history was decreased if compared with 0.71±0.19 μM exhaled H2O2 in CAP group (p=0.005). On the contrary, TBARs concentration evaluated over entire study period was increased in smoking CAP patients (median 0.02 μM, range 0-0.32 μM) compared with non-smoking group (median 0.01 μM, range 0-0.21 μM, p<0.05). Concurrent, active smoking status was related with the decreased levels of H2O2 exhaled in breath condensate within the course of CAP but it appeared to increase levels of TBARs. Conclusions. The differential alternations of oxidative parameters in EBC with respect to the smoking status might provide evidence of increased H2O2 decomposition and enhanced generation of reactive species in airways of CAP patients

Quercetin prevents progression of disease in elastase/LPS-exposed mice by negatively regulating MMP expression

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, emphysema and irreversible airflow limitation. These changes are thought to be due to oxidative stress and an imbalance of proteases and antiproteases. Quercetin, a plant flavonoid, is a potent antioxidant and anti-inflammatory agent. We hypothesized that quercetin reduces lung inflammation and improves lung function in elastase/lipopolysaccharide (LPS)-exposed mice which show typical features of COPD, including airways inflammation, goblet cell metaplasia, and emphysema. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0.5 mg of quercetin dihydrate or 50% propylene glycol (vehicle) by gavage for 10 days. Lungs were examined for elastance, oxidative stress, inflammation, and matrix metalloproteinase (MMP) activity. Effects of quercetin on MMP transcription and activity were examined in LPS-exposed murine macrophages. Results Quercetin-treated, elastase/LPS-exposed mice showed improved elastic recoil and decreased alveolar chord length compared to vehicle-treated controls. Quercetin-treated mice showed decreased levels of thiobarbituric acid reactive substances, a measure of lipid peroxidation caused by oxidative stress. Quercetin also reduced lung inflammation, goblet cell metaplasia, and mRNA expression of pro-inflammatory cytokines and muc5AC. Quercetin treatment decreased the expression and activity of MMP9 and MMP12 in vivo and in vitro, while increasing expression of the histone deacetylase Sirt-1 and suppressing MMP promoter H4 acetylation. Finally, co-treatment with the Sirt-1 inhibitor sirtinol blocked the effects of quercetin on the lung phenotype. Conclusions Quercetin prevents progression of emphysema in elastase/LPS-treated mice by reducing oxidative stress, lung inflammation and expression of MMP9 and MMP12.http://deepblue.lib.umich.edu/bitstream/2027.42/78260/1/1465-9921-11-131.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78260/2/1465-9921-11-131.pdfPeer Reviewe

No evidence of enhanced oxidant production in blood obtained from patients with obstructive sleep apnea

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea syndrome (OSAS) is a recognized risk factor for cardiovascular morbidity and mortality, perhaps due to causative exacerbations of systemic oxidative stress. Putative oxidative stress related to numerous episodes of intermittent hypoxia, may be an oxidants chief driving force in OSAS patients.</p> <p>Methods</p> <p>We assessed the resting and n-formyl-methionyl-leucyl-phenylalanine (fMLP)- induced whole blood chemiluminescence (as a measure of oxidant production by polymorphonuclear leukocytes and monocytes), ferric reducing ability of plasma (FRAP) and H₂O₂generation in the whole blood of 27 untreated OSAS patients, 22 subjects after a night of CPAP therapy and 11 controls without OSAS. All of them were matched to age, BMI (body mass index) and smoking habits. All parameters were measured before and after polysomnography-controlled sleep, individual results were obtained as a mean from duplicated experiments.</p> <p>Results</p> <p>No significant differences were distinguished between evening and morning blood chemiluminescence, H₂O₂activity and FRAP within and between all three study groups.</p> <p>For instance patients with untreated OSAS had similar morning and evening resting whole blood chemiluminescence (2.3 +/- 2.2 vs. 2.4 +/- 2.2 [aU·10^-4phagocytes]), total light emission after stimulation with fMLP (1790 +/- 1371 vs. 1939 +/- 1532 [aU·s·10^-4phagocytes]), as well as FRAP after 3 min. plasma incubation (602 +/- 202 vs. 671 +/- 221 [uM]). Although, in the subgroup of 11 patients with severe OSAS (apnea/hypopnea index 58 +/- 18/h and oxygen desaturation index 55 +/- 19/h), the morning vs. evening resting chemiluminescence and total light emission after stimulation with fMLP observed a propensity to elevate 2.5 +/- 2.7 vs. 1.9 +/- 1.8 [aU·10^-4phagocytes] and 1778 +/- 1442 vs. 1503 +/- 1391 [aU·s·10^-4phagocytes], respectively, these did not attain statistical significance (p > 0.05).</p> <p>Conclusion</p> <p>Our investigation exposed no evidence in the overproduction of oxidants via circulating phagocytes, once considered a culprit in the oxidative stress of OSAS patients.</p