Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556


Antioxidant Therapeutic Targets in COPD

Author(s): Irfan Rahman and Iain Kilty

Affiliation: Department of EnvironmentalMedicine, Division of Lung Biology and Disease, University of RochesterMedical Center, 601 Elmwood Ave., Box 850, Rochester, NY 14642, USA.

Keywords: Reactive Oxygen Species, lipid peroxides, polyphenols, glutathione, antioxidants, NF-kB, corticosteroids, Chronic Obstructive Pulmonary Disease, lungs


Oxidative stress and chronic inflammation are important features in the pathogenesis of chronic obstructive pulmonary disease (COPD). Oxidative stress has important consequences for several elements of lung physiology and for the pathogenesis of COPD, including oxidative inactivation of antiproteases and surfactants, mucus hypersecretion, membrane lipid peroxidation, alveolar epithelial injury, remodeling of extracellular matrix, and apoptosis. Therefore, targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD. Antioxidant and/or anti-inflammatory agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenol (curcumin-diferuloylmethane, a principal component of turmeric), resveratrol (a flavanoid found in red wine), green tea (theophylline and epigallocatechin-3- gallate), ergothioneine (xanthine and peroxynitrite inhibitor), quercetin, erdosteine and carbocysteine lysine salt, have been reported to control NF-kB activation, regulation of glutathione biosynthesis genes, chromatin remodeling and hence inflammatory gene expression. Specific spin traps such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), manganese (III) meso-tetrakis (N,N-diethyl-1,3-imidazolium-2-yl) porphyrin (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed.

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Article Details

Page: [707 - 720]
Pages: 14
DOI: 10.2174/138945006777435254