Glutathione Peroxidase in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by a state of persistent inflammation and oxidative stress. The presence of oxidative stress in COPD is the result of an imbalance between pro-oxidant and antioxidant mechanisms. The aim of this review was to investigate a possible association between glutathione peroxidase (GPx), a key component of antioxidant defense mechanisms, and COPD. A systematic search for relevant studies was conducted in the electronic databases PubMed, Web of Science, Scopus, and Google Scholar, from inception to June 2021. Standardized mean differences (SMDs) were used to express the differences in GPx concentrations between COPD patients and non-COPD subjects. Twenty-four studies were identified. In 15 studies assessing whole blood/erythrocytes (GPx isoform 1), the pooled results showed that GPx concentrations were significantly lower in patients with COPD (SMD = −1.91, 95% CI −2.55 to −1.28, p < 0.001; moderate certainty of evidence). By contrast, in 10 studies assessing serum/plasma (GPx isoform 3), the pooled results showed that GPx concentrations were not significantly different between the two groups (very low certainty of evidence). The concentration of GPx-1, but not GPx-3, is significantly lower in COPD patients, suggesting an impairment of antioxidant defense mechanisms in this group.

The Emerging Clinical Significance of the Red Cell Distribution Width as a Biomarker in Chronic Obstructive Pulmonary Disease: A Systematic Review

“…A common denominator in patients with COPD, atherosclerotic cardiovascular disease, and diabetes is the presence of local and systemic oxidative stress and increased inflammation [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Notably, there is evidence that inflammatory cytokines can inhibit the maturation of erythroid cells in the bone marrow, with the consequent release into the circulation of immature erythrocytes.…”

Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

“…Oxidative stress and inflammation are considered fundamental mediators of chronic obstructive pulmonary disease (COPD) pathophysiology (77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91). The lungs are directly exposed to tobacco smoke and air pollutants that are main sources of ROS.…”

“…The lungs are directly exposed to tobacco smoke and air pollutants that are main sources of ROS. ROS directly cause lung damage as a result of DNA, lipid, carbohydrate, and protein alterations, and activate local inflammatory responses that contribute to COPD development and progression (79)(80)(81)(82)(83). ROS can further activate epithelial cells and macrophages facilitating neutrophil, monocyte, and lymphocyte recruitment, and the recruited activated inflammatory cells subsequently enhance additional ROS generation, increasing the pro-oxidant burden (80)(81)(82)(83)(84)(85).…”

“…ROS directly cause lung damage as a result of DNA, lipid, carbohydrate, and protein alterations, and activate local inflammatory responses that contribute to COPD development and progression (79)(80)(81)(82)(83). ROS can further activate epithelial cells and macrophages facilitating neutrophil, monocyte, and lymphocyte recruitment, and the recruited activated inflammatory cells subsequently enhance additional ROS generation, increasing the pro-oxidant burden (80)(81)(82)(83)(84)(85). ROS and RNS production are facilitated by pattern recognition receptors [C-reactive protein (CRP), toll-like receptors] capable of recognizing pathogen (bacterial/viral)-associated molecular patterns and/or damage-associated molecular patterns in apoptotic or damaged cells (92-100) (Figure 6).…”

“…phosphocholine head group in phospholipids of normal healthy cell membranes is not accessible but, when cells are damaged and die, enhanced availability of lysophosphatidylcholine and disruption of the lipid bilayer expose phosphocholine residues to which CRP avidly binds (99). These events lead to a state of persistent inflammation and chronic oxidative stress (82)(83)(84)(85), characterized by increased ROS production, reduced GSH peroxidase activity, selenium deficiency and reduced GSH levels (80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91). Asymptomatic smokers and stable COPD patients showed increased GSH levels in bronchoalveolar lavage, while patients with severe/very severe exacerbation periods had significantly decreased levels (101).…”