Peroxynitrite Elevation in Exhaled Breath Condensate of COPD and Its Inhibition by Fudosteine

Background Peroxynitrite 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 ( Method 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 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)-1β-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. Conclusion 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.