title: Peroxynitrite elevation in exhaled breath condensate of COPD and its inhibition by fudosteine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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; p < 0.0001; 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Grace O
authors.initials: GO
authors.lastname: Osoata
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Hanazawa
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Caterina
authors.initials: C
authors.lastname: Brindicci
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Misako
authors.initials: M
authors.lastname: Ito
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Sergei
authors.initials: S
authors.lastname: Kharitonov
authors.affiliation: Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: k.ito@imperial.ac.uk.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D001944:Breath Tests; D016022:Case-Control Studies; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006207:Half-Life; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D010865:Pilot Projects; D011336:Probability; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000188:drug therapy*; D012016:Reference Values; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013183:Sputum / Q000166:cytology / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D003553:Cystine; C113797:fudosteine