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Published ahead of print on December 3, 2004, doi:10.1164/rccm.200404-558OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 838-843, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200404-558OC

Original Article

Lipid Peroxidation and 5-Lipoxygenase Activity in Chronic Obstructive Pulmonary Disease

Pierachille Santus, Alessandra Sola, Paolo Carlucci, Francesca Fumagalli, Antonio Di Gennaro, Michele Mondoni, Chiara Carnini, Stefano Centanni and Angelo Sala

Institute of Respiratory Medicine, Ospedale S. Paolo; and Department of Pharmacological Sciences, Center for Cardiopulmonary Pharmacology, University of Milan, Milan, Italy

Correspondence and requests for reprints should be addressed to Angelo Sala, Ph.D., Department of Pharmacological Sciences, Center for Cardiopulmonary Pharmacology, Via Balzaretti 9, Milan 20133, Italy. E-mail: angelo.sala{at}unimi.it

We studied the urinary excretion of the isoprostane 8-iso-prostaglandin F2{alpha} as an index of in vivo oxidant stress, and the production of leukotriene (LT) B4 (LTB4) by neutrophils in subjects with chronic obstructive pulmonary disease (COPD) and normal subjects. Overnight urinary excretion of the isoprostane was significantly higher in patients with COPD than in control subjects, and LTB4 production by challenge of neutrophils obtained from patients with COPD was also significantly higher than that observed in control neutrophils. Treatment with a standardized polyphenol extract caused a significant decrease in isoprostane excretion, accompanied by a statistically significant increase of PaO2. Furthermore, changes in FEV1 significantly correlated with the changes in isoprostane urinary excretion observed from enrollment to the end of treatment. The results of this study suggest that enhanced oxidative stress in subjects with COPD is paralleled by the increased ability of neutrophils to synthesize the chemotactic factor LTB4, and may ultimately contribute to the infiltration/activation of neutrophils into the airways of subjects with COPD. Antioxidant treatment in subjects with COPD is effective in reducing oxidant stress as shown by the decrease of urinary isoprostane, a reduction that correlates with the severity of the disease, as indicated by changes in PaO2 and FEV1.

Key Words: leukotriene B4 • natural polyphenols • neutrophils • oxidative stress • urinary isoprostanes




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