Xanthine oxidase inhibition reduces reactive nitrogen species production in COPD airways

Abstract

Reactive nitrogen species (RNS) have been reported to be involved in the inflammatory process in chronic obstructive pulmonary disease (COPD). However, there are no studies on the modulation of RNS in COPD. It was hypothesised that inhibition of xanthine oxidase (XO) might decrease RNS production in COPD airways through the suppression of superoxide anion production.Ten COPD and six healthy subjects participated in the study. The XO inhibitor allopurinol (300 mg?day -1 p.o. for 4 weeks) was administered to COPD patients. RNS production in the airway was assessed by 3-nitrotyrosine immunoreactivity and enzymic activity of XO in induced sputum as well as by exhaled nitric oxide (eNO) concentration.XO activity in the airway was significantly elevated in COPD compared with healthy subjects. Allopurinol administration to COPD subjects significantly decreased XO activity and nitrotyrosine formation. In contrast, eNO concentration was significantly increased by allopurinol administration.These results suggest that oral administration of the xanthine oxidase inhibitor allopurinol reduces airway reactive nitrogen species production in chronic obstructive pulmonary disease subjects. This intervention may be useful in the future management of chronic obstructive pulmonary disease. Eur Respir J 2003; 22: 457-461.

Exhaled breath condensate biomarkers in COPD

“…Mild steroid-naïve asthmatics had significantly higher levels of NT than healthy controls but levels were reduced in those treated with ICS with moderate and severe disease [78]. Although NT measurements have been performed in induced sputum of COPD patients, with increased levels compared with controls and inhibition by the xanthine oxidase inhibitor allopurinol, there have been no studies using this method in EBC from COPD patients [96]. Nitrosothiols Diagnosis Nitrosothiols (RS-NO) are measured using a commercially available assay (Oxonon; detection limit 0.025 mM) based on the cleavage of RS-NO to release NO, which upon rapid oxidation forms NO 2 -and is detected colourimetrically.…”

2. Advances in Pharmacotherapy for COPD

“…As the xanthine oxidase inhibitor reduces the reactive nitrogen species production, this agent may be useful for reducing the inflammatory and destructive process in COPD ( Fig. 1) (16).…”

The black box of lung redox

“…As discussed in the paper by ICHINOSE et al [1], there are multiple mechanisms to form O 2 -, one of which is XO. The authors identified that in subjects with COPD, the XO activity in induced sputum was four-fold higher than controls, and that this activity was effectively reduced by allopurinol.…”

“…INCHINOSE et al [1] in this issue of European Respiratory Journal, have in part overcome this hurdle. They measure only three components of the lung redox system (xanthine oxidase (XO), NO, and nitrotyrosine), by necessity leaving the remainder unassessed.…”

“…These processes can indeed be blocked. Although it remains to be determined if nitration is causally relevant to human lung disease in vivo, ICHINOSE et al [1] have provided sound evidence that it is relevant at least to exhaled nitric oxide measures. Additionally, they have reported a simple human system that has given clinical credence to many preceding redox studies at the bench.…”