Article

Antioxidant therapeutic targets in COPD

Department of Environmental Medicine, Division of Lung Biology and Disease, University of Rochester Medical Center, 601 Elmwood Ave., Box 850, Rochester, NY 14642, USA.
Current Drug Targets (Impact Factor: 3.6). 07/2006; 7(6):707-20. DOI: 10.2174/138945006777435254
Source: PubMed

ABSTRACT 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.

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    • "Subsequently, this increased intracellular ROS may activate various ROSsensitive signaling pathways, such as the mitogen-activated protein kinases (MAPKs) and a number of downstream transcriptional factors, such as nuclear factor-í µí¼…B (NF-í µí¼…B), and ultimately promote inflammatory gene expression [4, 6– 12]. The involvement of the ROS-sensitive signaling pathways suggests that therapeutic targeting of oxidative stress with antioxidants in order to improve lung inflammation should be beneficial when treating COPD [13] "
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    • "Subsequently, this increased intracellular ROS may activate various ROSsensitive signaling pathways, such as the mitogen-activated protein kinases (MAPKs) and a number of downstream transcriptional factors, such as nuclear factor-í µí¼…B (NF-í µí¼…B), and ultimately promote inflammatory gene expression [4, 6– 12]. The involvement of the ROS-sensitive signaling pathways suggests that therapeutic targeting of oxidative stress with antioxidants in order to improve lung inflammation should be beneficial when treating COPD [13] "
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