Oxidative Damage and Antioxidant Mechanisms in COPD
Condition: Respiratory Diseases
MeSH terms: Respiratory Tract Diseases; Respiration Disorders
Study type: Observational

Summary: 
      The environmental pollutants and endogenous reactive oxygen metabolites from inflammatory
      cells exert substantial pathological effects on the lung cells [1]. Oxidative stress (OS) is
      a major factor that plays a significant role in lung cancer (LC) [2], chronic obstructive
      pulmonary disease (COPD) [3] and obstructive sleep apnea syndrome (OSAS) [4, 5]. The current
      evidence suggests that OS takes part in the mechanisms involved in initiation, promotion and
      progression of respiratory diseases. The major exposures that cause OS can be summarized as
      smoking, and ambient air pollution that contains particulate matter smaller than aerodynamic
      diameter of 2.5 µm [6-8]. Epidemiological and clinical studies showed that the overall
      outcome of pulmonary OS is increased mortality due to increased incidence of respiratory
      diseases [9].
    

Detailed description: 
      Introduction Lung is a particularly important organ because of its interface with the
      environment. The environmental pollutants and endogenous reactive oxygen metabolites from
      inflammatory cells exert substantial pathological effects on the lung cells [1]. Oxidative
      stress (OS) is a major factor that plays a significant role in lung cancer (LC) [2], chronic
      obstructive pulmonary disease (COPD) [3] and obstructive sleep apnea syndrome (OSAS) [4, 5].
      The current evidence suggests that OS takes part in the mechanisms involved in initiation,
      promotion and progression of respiratory diseases. The major exposures that cause OS can be
      summarized as smoking, and ambient air pollution that contains particulate matter smaller
      than aerodynamic diameter of 2.5 µm [6-8]. Epidemiological and clinical studies showed that
      the overall outcome of pulmonary OS is increased mortality due to increased incidence of
      respiratory diseases [9].

      In OSAS, an episodic hypoxia-reoxygenation cycle occurs during intermittent nocturnal
      hypoxias that causes the production of reactive oxygen metabolites [10]. These metabolites
      are responsible for the activation of inflammatory cells in OSAS [11, 12], and their
      increased levels eventually cause ischemia-reperfusion injury [13], and cellular and DNA
      damage [14, 15]. The latter, is also a significant contributor of LC progression. The DNA
      damage in the presence of reactive oxygen metabolites yields carcinogenesis by several
      mechanisms. Some of them are single or double-stranded DNA breaks, and modifications in
      purines or pyrimidines. Nevertheless, OS is not the only susceptible factor for
      carcinogenesis, there are also many other pathological mechanisms contributing to cancer
      development, such as reactive nitrogen species, and involvement of mitochondrial DNA
      mutations [16] in inflammatory conditions. Previous studies reported that LC occurs
      two-to-five times higher in patients with moderate-to-severe COPD [17, 18]. OS is also the
      main etiological factor of COPD, which is particularly important in the acute exacerbations
      of the disease [19]. The parenchymal damage in COPD includes some mechanisms such as chronic
      inflammation, OS, deteriorations in the balance of protease and antiprotease activities, and
      apoptosis [20]. The major etiological factor that suspected to play role in the progression
      of LC in COPD is reported as chronic inflammation, which causes induction of several
      interleukins and cyclooxygenase-2 activity. The inflammatory micro-environment is a potential
      medium for contributing the neoproliferative process, which interacts with regulatory
      mechanism such as apoptosis and angiogenesis [21].

      Some biomarkers are available for evaluating the OS in the living organisms [22]. Some of
      these biomarkers are malondialdehyde (MDA), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG), and
      coenzyme Q10 (CoQ10). Each of these biomarkers is involved in oxidative processes. MDA is a
      by-product of polyunsaturated fatty acid peroxidation [23]. Lipid peroxidation is the
      oxidation reactions between reactive oxygen metabolites and polyunsaturated fatty acids,
      which eventually causes changes in the structure and permeability of lung membrane [24]. The
      second biomarker, 8-OHdG, is primarily involved in DNA damage. The mechanism for this damage
      is the guanine: cytosine to adenine: thymine transversion on DNA replication [25], which
      induces microsatellite instability, and abnormal apoptosis or necrosis [26]. The third
      biomarker is CoQ10, which is also a mediator of lipid peroxidation, and an essential cofactor
      in the electron-transport chain (ETC). It is also a lipophilic antioxidant component of the
      lipid membranes [27]. In this study.
    

Intervention name(s): oxidative and antioxidant biomarkers
Intervention type(s): Genetic
Intervention description(s): the oxidative damage in these diseases by evaluating the oxidative and antioxidant biomarkers.
Intervention MeSH terms: Antioxidants
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        A total of 111 participants (35 females, 76 males) with OSAS (n=29), COPD (n=26) and LC
        (n=28), and healthy controls (n=28) were included in the study.
      
Keywords: lung cancer; antioxidants; oxidative damage