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Year: 2009  |  Volume: 135  |  Issue: 6  |  Page No.: 1513 - 1520

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

G. O Osoata, T Hanazawa, C Brindicci, M Ito, P. J Barnes, S Kharitonov and K. Ito    

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.

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 < 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 (FEV1) 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 H2O2 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.

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