Table 1.

Main mechanisms of oxidative-burden related COPD

Mechanism	Outcome	Refs.
Imbalance of biological molecules	Reduced antioxidant and antiprotease enzyme activity (SOD, CAT, GPx, α1 antitrypsin); Altered expression of ROS-related enzymes (decreased in CAT, GPx, SOD, and increase in iNOS); Activation of metallo proteinases	[45–49]
Intracellular signaling	Altered expression of ROS related enzymes (decreased in CAT, GPx, SOD, and increase in iNOS)	[50, 51]
Mitochondrial respiration	Altered mitochondrial function	[46, 48, 52, 53]
Upregulation of gene transcription (NF-κB and, AP-1) and increase in cellular cytokine production	Increased gene expression of inflammatory mediators and cytokines (IL-1, TNF-α, IL-8, GM-CSF, iNOS)	[54]
Nuclear histone acetylation/deacetylation balance	Decreased HDAC2 activity and protein expression chronic inflammation (chronic remodelling)	[55, 56]
Remodelling of DNA/chromatin	Decreased histone deacetylase 2	[57]

iNOS, inducible nitric oxide synthase isoenzymes; SLPI, secretory leukocyte protease inhibitor; α1AT, alpha-1-antitrypsin; IL-1, interleukin 1; NF-κB, nuclear factor kappa B; IL-8, interleukin-8; GM-CSF, TNF-α, tumor necrosis factor-α; granulocyte macrophage colony-stimulating factor; iNOS, inducible nitric oxide synthase; HDAC: histone deacetylase