Oxidative Stress in COPD

Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

Oxidative stress is now recognized to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and indoor air pollution and due to endogenous generation of reactive oxygen species (ROS) by inflammatory and structural cells in the lung. Mitochondrial oxidative stress may be particularly important in COPD. At the same time there is a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factor Nrf2 that regulates multiple antioxidant genes. There is also increased systemic oxidative stress that may exacerbate co-morbidities and contribute to skeletal muscle weakness. Oxidative stress amplifies chronic infection through the activation of pro-inflammatory transcription factors and enzymes, promotes fibrosis (small airway obstruction) and through reduced antiproteases potentiates the effects of elastases (emphysema). Oxidative stress also causes corticosteroid resistance through reduced expression of histone deacetylase-2 and accelerates ageing through the reduction in sirtuin-1. In addition it promotes DNA damage and impairs DNA repair which may predispose to the development of lung cancer. ROS lead to formation of aldehydes through lipid peroxidation resulting in ‘carbonyl stress’ and the covalent modification of proteins that may then generate autoantibodies that could further damage the lung. This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD. Currently used antioxidants are poorly effective, so there is a search for more potent and safe antioxidants or for drugs that restore the activity of Nrf2.

Keywords

Oxidative Stress Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease Patient Protein Carbonylation Exhale Breath Condensate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

4HNE

4-Hydroxy-2-nonenal

FEV1

Forced expiratory volume in 1 second

GSH

Glutathione

GST

Glutathione-S-transferase

H2O2

Hydrogen peroxide

HDAC

Histone deacetylase

IL

Interleukin

MDA

Malondialdehyde

NF-κB

Nuclear factor-κB

NOX

NADPH oxidase

Nrf2

Nuclear erythroid-2-related factor 2

ROS

Reactive oxygen species

SOD

Superoxide dismutase

TGF

Transforming growth factor

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Airway Disease SectionNational Heart and Lung Institute, Imperial College LondonLondonUK

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