Peroxynitrite Elevation in Exhaled Breath Condensate of COPD and Its Inhibition by Fudosteine
| Autor: | Caterina Brindicci, Toyoyuki Hanazawa, Grace O. Osoata, Misako Ito, Kazuhiro Ito, Peter J. Barnes, Sergei A. Kharitonov |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Pulmonary and Respiratory Medicine Enzyme-Linked Immunosorbent Assay Pilot Projects Pharmacology Nitric Oxide Critical Care and Intensive Care Medicine Sensitivity and Specificity Severity of Illness Index Nitric oxide Superoxide dismutase Pulmonary Disease Chronic Obstructive chemistry.chemical_compound Reference Values Peroxynitrous Acid medicine Humans Exhaled breath condensate Bovine serum albumin Aged Probability COPD biology Superoxide business.industry Interleukin-8 Sputum Middle Aged medicine.disease Respiratory Function Tests respiratory tract diseases Oxidative Stress Breath Tests chemistry Case-Control Studies Anesthesia biology.protein Cystine Female Inflammation Mediators medicine.symptom Cardiology and Cardiovascular Medicine business Peroxynitrite Half-Life |
| Zdroj: | Chest. 135:1513-1520 |
| ISSN: | 0012-3692 |
| DOI: | 10.1378/chest.08-2105 |
| Popis: | Peroxynitrite (PN) formed by the reaction of nitric oxide and superoxide is a powerful oxidant/nitrosant. Nitrative stress is implicated in COPD pathogenesis, but PN has not been detected due to a short half-life (1 s) at physiologic condition. Instead, 3-nitrotyrosine has been measured as a footprint of PN release.PN was measured using oxidation of 2',7'-dichlorofluorescein (DCDHF) in exhaled breath condensate (EBC) collected in high pH and sputum cells. The PN scavenging effect was also evaluated by the same system as PN-induced bovine serum albumin (BSA) nitration.The mean (+/- SD) PN levels in EBC of COPD patients (7.9 +/- 3.0 nmol/L; n = 10) were significantly higher than those of healthy volunteers (2.0 +/- 1.1 nmol/L; p0.0001; n = 8) and smokers (2.8 +/- 0.9 nmol/L; p = 0.0017; n = 6). There was a good correlation between PN level and disease severity (FEV(1)) in COPD (p = 0.0016). Fudosteine (FDS), a unique mucolytic antioxidant, showed a stronger scavenging effect of PN than N-acetyl-cysteine on DCDHF oxidation in vitro and in sputum macrophages, and also on PN-induced BSA nitration. FDS (0.1 mmol/L) reduced PN-enhanced interleukin (IL)-1beta-induced IL-8 release and restored corticosteroid sensitivity defected by PN more potently than those induced by H(2)O(2) in A549 airway epithelial cells.This noninvasive PN measurement in EBC may be useful for monitoring airway nitrative stress in COPD. Furthermore, FDS has the potential to inhibit PN-induced events in lung by its scavenging effect. |
| Databáze: | OpenAIRE |
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