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Xanthine oxidase inhibition reduces reactive nitrogen species production in COPD airways

¹ Third Dept of Internal Medicine, Wakayama Medical University, Wakayama, ² Division of Respiratory and Infectious Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan. ³ Dept of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK

CORRESPONDENCE: M. Ichinose, Third Dept of Internal Medicine, Wakayama Medical University, Wakayama 811-1, Japan. Fax: 81 734462877. E-mail: masakazu@wakayama-med.ac.jp

Keywords: chronic obstructive pulmonary disease, exhaled nitric oxide, nitrotyrosine

Received: June 19, 2002
Accepted April 13, 2003

This study was supported by Science Research Grants 12470132 and 14657143 from the Ministry of Education, Culture, Sports, Science and Technology, Tokyo, Japan.

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.

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