The Role of Mitochondria and Oxidative/Antioxidative Imbalance in Pathobiology of Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. The major risk factor of COPD, which has been proven in many studies, is the exposure to cigarette smoke. However, it is 15–20% of all smokers who develop COPD. This is why we should recognize the pathobiology of COPD as involving a complex interaction between several factors, including genetic vulnerability. Oxidant-antioxidant imbalance is recognized as one of the significant factors in COPD pathogenesis. Numerous exogenous and endogenous sources of ROS are present in pathobiology of COPD. One of endogenous sources of ROS is mitochondria. Although leakage of electrons from electron transport chain and forming of ROS are the effect of physiological functioning of mitochondria, there are various intra- and extracellular factors which may increase this amount and significantly contribute to oxidative-antioxidative imbalance. With the coexistence with impaired antioxidant defence, all these issues lead to oxidative and carbonyl stress. Both of these states play a significant role in pathobiology of COPD and may account for development of major comorbidities of this disease.

Gene expression profile of human lung in a relatively early stage of COPD with emphysema

“…One endogenous source of ROS is mitochondria. Although the leakage of electrons from the electron transport chain and the formation of ROS result from the physiological functioning of mitochondria, there are various intra- and extracellular factors that may increase these amounts and significantly contribute to oxidative–antioxidative imbalance 39. Proteasome complex-related genes were also decreased in expression in the COPD with emphysema group in the present study.…”

Clinical effects of chemical exposures on mitochondrial function

“…The contribution of mitochondrial dysfunction has been reported in major environment-related multifactorial diseases, such as respiratory disease (Bialas et al, 2016), viral infections (Wnek et al, 2016), neurological disorders (Giannoccaro et al, 2017, Swerdlow et al, 2017), cardiovascular diseases (Sabbah, 2016), and cancer (Srinivasan et al, 2017). Although harmful exposure to environmental pollutants is ubiquitous among all populations, disease manifestation occurs in only a subset of the population.…”

Oxidative stress and its possible relation to lower urinary tract functional pathology

“…Many studies have been devoted to the occurrence of and consequences of oxidative stress in various organ/systems such as cancer , CNS , cardiovascular system , lung , and kidney . Involvement in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis have been demonstrated, and the developments in the search for effective therapeutic agents that target redox homeostasis, such as inhibitors of NOXs that are likely candidates for clinical use, have recently been discussed .…”