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Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, S58-S65

Oxidants and Antioxidants as Therapeutic Targets in Chronic Obstructive Pulmonary Disease

WILLIAM MACNEE and IRFAN RAHMAN

Respiratory Medicine, ELEGI and Colt Research Laboratories, University of Edinburgh, Edinburgh, Scotland

AM J RESPIR CRIT CARE MED 1999;160:S58-S65.There is now increasing evidence that an oxidant/antioxidant imbalance, in favor of oxidants, occurs in chronic obstructive pulmonary disease (COPD). Evidence is also accumulating that oxidative stress is a critical event in the pathogenesis of this condition. A large number of studies have demonstrated an increased oxidant burden and consequently increased markers of oxidative stress in the airspaces, breath, blood, and urine of smokers and of patients with COPD. There are several events related to oxidative stress, which are important in the pathogenesis of COPD. These include oxidative inactivation of antiproteinases, airspace epithelial injury, increased sequestration of neutrophils in the pulmonary microvasculature, and gene expression of proinflammatory mediators. Oxidative processes have a fundamental role in the inflammation of smokers and patients with COPD, through redox-sensitive transcription factors such as NF-kappa B and AP-1, which regulate the genes for proinflammatory mediators and protective mechanisms, such as antioxidant gene expression. In addition to the oxidative stress produced by cigarette smoking, dietary deficiency in antioxidants is related to the development of airflow limitation, and hence dietary supplementation may be a beneficial therapeutic intervention in this condition. The use of antioxidants with good bioavailability or molecules that have antioxidant enzyme activity may be treatments that not only protect against the direct injurious effects of oxidants, but may fundamentally alter the inflammatory events that are thought to play an important part in the pathogenesis of COPD. MacNee W, Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease.




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