Respiratory Diseases Clinical Trial
Official title:
Evaluation of Oxidative Damage and Antioxidant Mechanisms in COPD, Lung Cancer, and Obstructive Sleep Apnea Syndrome
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].
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.
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