Reactive Oxygen Species in Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) includes chronic bronchitis and emphysema. Environmental exposure, primarily cigarette smoking, can cause high oxidative stress and is the main factor of COPD development. Cigarette smoke also contributes to the imbalance of oxidant/antioxidant due to exogenous reactive oxygen species (ROS). Moreover, endogenously released ROS during the inflammatory process and mitochondrial dysfunction may contribute to this disease progression. ROS and reactive nitrogen species (RNS) can oxidize different biomolecules such as DNA, proteins, and lipids leading to epithelial cell injury and death. Various detoxifying enzymes and antioxidant defense systems can be involved in ROS removal. In this review, we summarize the main findings regarding the biological role of ROS, which may contribute to COPD development, and cytoprotective mechanisms against this disease progression.

Figure 1

Potential contribution of ROS to various lung disease development. ROS—reactive oxygen species; COPD—chronic obstructive pulmonary disease; ARDS—acute respiratory distress syndrome.

Figure 2

Exogenous and endogenous sources of ROS such as superoxide anions, hydrogen peroxide, hydroxyl radicals, and hypochlorous acid in cells.

Figure 3

ROS reaction with various biomolecules such as proteins, lipids, and DNA may cause cell injury leading to apoptosis and necrosis.

Figure 4

The mechanism of ROS interaction with biomolecules. (a) Hypochlorite anion production catalyzed by myeloperoxidase; (b) lipid peroxidation; (c) production of hydrogen peroxide; (d) peroxynitrite generation; (e) production of alkyl peroxynitrites. H₂O₂—hydrogen peroxide; ⁻OCl—hypochlorite anion; RH—unsaturated lipid; ^•OH—hydroxyl radical; R^•—lipid radical; ROO^•—lipid peroxyl radical; ROOH—lipid peroxide; Q/QH₂—quinone/hydroquinone; O₂^•−—superoxide anion; NO^•—nitric oxide; ONOO⁻—peroxynitrite; ROONO—alkyl peroxynitrites.

Figure 5

Primary enzymatic means of ROS detoxification. The relative reactivity of the ROS is indicated by color, ranging from highly reactive (red) to inert (green). SOD—superoxide dismutases; Prxs—peroxiredoxins; Gpxs—glutathione peroxidases.