DNA Damage Due to Oxidative Stress in Chronic Obstructive Pulmonary Disease (COPD)

Abstract

According to the American Thorasic Society (ATS)/European Respiratory Society (ERS) Statement, chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with a strong genetic component, characterized by airflow limitation that is not fully reversible, but is usually progressive and associated with an enhanced inflammatory response of the lung to noxious particles or gases. The main features of COPD are chronic inflammation of the airways and progressive destruction of lung parenchyma and alveolar structure. The pathogenesis of COPD is complex due to the interactions of several mechanisms, such as inflammation, proteolytic/antiproteolytic imbalance, oxidative stress, DNA damage, apoptosis, enhanced senescence of the structural cells and defective repair processes. This review focuses on the effects of oxidative DNA damage and the consequent immune responses in COPD. In susceptible individuals, cigarette smoke injures the airway epithelium generating the release of endogenous intracellular molecules or danger-associated molecular patterns from stressed or dying cells. These signals are captured by antigen presenting cells and are transferred to the lymphoid tissue, generating an adaptive immune response and enhancing chronic inflammation.

The link between chronic periodontitis and COPD: a common role for the neutrophil?

“…Cigarette smoke contains large amounts of oxidants and free radicals that are a major part of the oxidative stress endured by host cells [89]. In addition to these exogenous sources, activated inflammatory cells such as macrophages and neutrophils generate ROS in response to environmental insults, as well as in response to bacteria and their products [90].…”

Respiratory viral infection: a potential “missing link” in the pathogenesis of COPD

“…Combustion products from biomass fuel, occupational dust and particulate matter from air pollution are important risk factors in non-smokers [3,13,14]. There is extensive evidence demonstrating that both protease/anti-protease imbalance and oxidative stress are viable pro-inflammatory mechanisms that contribute to pathogenesis in COPD [15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Only a proportion of smokers develop COPD suggesting that host factors may also be implicated in disease pathogenesis [29,30].…”

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

“…OS‐induced damage to DNA also contributes to neurodegeneration, promoting Parkinson's disease, Alzheimer's disease, and sporadic amyotrophic lateral sclerosis . Other health disorders arising from oxidative damage to DNA are cardiovascular diseases, Wilson's disease, Huntington's disease, inflammatory bowel disease, acquired immunodeficiency syndrome, diabetes and its complications, chronic obstructive pulmonary disease, and rheumatoid arthritis …”

“…6 OS-induced damage to DNA also contributes to neurodegeneration, promoting Parkinson's disease, [7][8][9] Alzheimer's disease, [10][11][12] and sporadic amyotrophic lateral sclerosis. 13 Other health disorders arising from oxidative damage to DNA are cardiovascular diseases, [14][15][16][17] Wilson's disease, 18,19 Huntington's disease, 20,21 inflammatory bowel disease, 22,23 acquired immunodeficiency syndrome, 24,25 diabetes 26 and its complications, [27][28][29] chronic obstructive pulmonary disease, 30 and rheumatoid arthritis. [31][32][33] The hydroxyl radical (˙OH) has been held responsible for the most common oxidative damage to DNA, 34,35 which involves different chemical routes and yields diverse products (Scheme 1).…”