Antioxidant therapeutic targets in COPD.
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-kappaB activation, regulation of glutathione biosynthesis genes, chromatin remodeling and hence inflammatory gene expression. Specific spin traps such as alpha-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.
Rahman
Irfan
I
Department of Environmental Medicine, Division of Lung Biology and Disease, University of Rochester Medical Center, 601 Elmwood Ave., Box 850, Rochester, NY 14642, USA. irfan_rahman@urmc.rochester.edu
Kilty
Iain
I
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects; D016896:Treatment Outcome
D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D014028:Tobacco Smoke Pollution