Oxidative Stress in Chronic Obstructive Pulmonary Disease

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 15945

Special Issue Editor

Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
Interests: COPD; oxidant stress; inflammation; signal transduction protease-anti-protease imbalance; autophagy

Special Issue Information

Dear Colleagues,

Chronic obstructive pulmonary disease (COPD), caused by exposure to noxious irritants including cigarette smoke (CS), is a progressive inflammatory disease characterized by persistent respiratory symptoms and airflow limitation. The pathogenesis of COPD is complex. As CS itself contains a high concentration of reactive oxygen species (ROS), there is a long history linking oxidative stress with COPD. Under normal conditions in the respiratory tract, it is now appreciated that ROS play a variety of physiological roles in signal transduction, injury-repair response, ECM remodeling, and pathogen clearance. In a pathologic conditions, ROS causes cell injury, mitochondrial dysfunction, formation, and release of toxic metabolites and even DNA damage. To protect themselves from ROS, cells contain antioxidant defenses including superoxide dismutase, catalase, and glutathione peroxidase to neutralize ROS. When ROS production exceeds antioxidant capacity, proteins, lipids, and nucleic acids become oxidized and often trigger an adaptive stress response. Moreover, crosstalk among oxidative stress, protease, and inflammation, which is called pathogenic triad, has been recently suggested to potentiate their deleterious effects. However, there are still many issues which need to be clarified in the pathogenic mechanism of oxidative stress in COPD.

As Guest Editor, I invite you to contribute to the Special Issue on “Oxidative Stress in Chronic Obstructive Pulmonary Disease”. Original research reports and reviews will be published online in Antioxidants.

Prof. Dr. Chul Gyu Yoo
Guest Editor

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Keywords

  • COPD
  • oxidative stress
  • antioxidants
  • inflammation
  • protease

Published Papers (7 papers)

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Research

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12 pages, 1862 KiB  
Article
Hypoxia Enhances Oxidative Stress in Neutrophils from ZZ Alpha-1 Antitrypsin Deficiency Patients
by María Magallón, Silvia Castillo-Corullón, Lucía Bañuls, Daniel Pellicer, Teresa Romero, Carlos Martínez-Ferraro, María Mercedes Navarro-García, Alberto Herrejón, Cruz González and Francisco Dasí
Antioxidants 2023, 12(4), 872; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12040872 - 03 Apr 2023
Cited by 1 | Viewed by 1240
Abstract
Alpha-1 antitrypsin deficiency (AATD) is a neutrophilic inflammatory disorder that may result in local hypoxia, reactive oxygen and nitrogen species (ROS/RNS) production, and increased damage in adjacent tissues. This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in [...] Read more.
Alpha-1 antitrypsin deficiency (AATD) is a neutrophilic inflammatory disorder that may result in local hypoxia, reactive oxygen and nitrogen species (ROS/RNS) production, and increased damage in adjacent tissues. This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in AATD patients. Neutrophils were isolated from AATD patients and control volunteers and exposed to hypoxia (1% O2 for 4 h), ROS/RNS, mitochondrial parameters, and non-enzymatic antioxidant defenses measured by flow cytometry. The expression of enzymatic antioxidant defenses was determined by qRT-PCR. Our results indicate that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione reductase. Likewise, our results show a decrease in mitochondrial membrane potential, indicating that this organelle could be involved in the production of the reactive species observed. No decrease in glutathione and thiol levels were observed. The accumulation of substances with high oxidative capacity would explain the greater oxidative damage observed in proteins and lipids. In conclusion, our results indicate that, compared to MM control individuals, ZZ-AATD neutrophils show increased ROS/RNS production under hypoxic conditions opening a new rationale for using antioxidant therapies to treat the disease. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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17 pages, 3200 KiB  
Article
Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation
by Eun-Young Heo, Kyoung-Hee Lee, Jisu Woo, Jiyeon Kim, Chang-Hoon Lee, Kyung-Jin Lee, Yun-Kyu Kim and Chul-Gyu Yoo
Antioxidants 2022, 11(10), 1980; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11101980 - 04 Oct 2022
Viewed by 1400
Abstract
Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found [...] Read more.
Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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Review

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29 pages, 1258 KiB  
Review
The Role of Oxidative Stress and Antioxidants in Cardiovascular Comorbidities in COPD
by Zsuzsanna Miklós and Ildikó Horváth
Antioxidants 2023, 12(6), 1196; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12061196 - 31 May 2023
Cited by 3 | Viewed by 2006
Abstract
Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in disease pathomechanisms. Unbalance between oxidants and antioxidant defense mechanisms amplifies the local inflammatory processes, worsens cardiovascular health, and [...] Read more.
Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in disease pathomechanisms. Unbalance between oxidants and antioxidant defense mechanisms amplifies the local inflammatory processes, worsens cardiovascular health, and contributes to COPD-related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures, with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced, with some suggestions for further research in the field. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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16 pages, 737 KiB  
Review
Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease
by Lauren H. Fairley, Shatarupa Das, Vivek Dharwal, Nadia Amorim, Karl J. Hegarty, Ridhima Wadhwa, Guntipally Mounika and Philip M. Hansbro
Antioxidants 2023, 12(4), 973; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12040973 - 21 Apr 2023
Cited by 3 | Viewed by 2336
Abstract
Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of [...] Read more.
Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging and cellular senescence. Evidence suggests that oxidative damage is not solely due to exogenous exposure to inhaled irritants, but also endogenous sources of oxidants in the form of reactive oxygen species (ROS). Mitochondria, the major producers of ROS, exhibit impaired structure and function in COPD, resulting in reduced oxidative capacity and excessive ROS production. Antioxidants have been shown to protect against ROS-induced oxidative damage in COPD, by reducing ROS levels, reducing inflammation, and protecting against the development of emphysema. However, currently available antioxidants are not routinely used in the management of COPD, suggesting the need for more effective antioxidant agents. In recent years, a number of mitochondria-targeted antioxidant (MTA) compounds have been developed that are capable of crossing the mitochondria lipid bilayer, offering a more targeted approach to reducing ROS at its source. In particular, MTAs have been shown to illicit greater protective effects compared to non-targeted, cellular antioxidants by further reducing apoptosis and offering greater protection against mtDNA damage, suggesting they are promising therapeutic agents for the treatment of COPD. Here, we review evidence for the therapeutic potential of MTAs as a treatment for chronic lung disease and discuss current challenges and future directions. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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16 pages, 8215 KiB  
Review
Oxidative Stress in Chronic Obstructive Pulmonary Disease
by Peter J. Barnes
Antioxidants 2022, 11(5), 965; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11050965 - 13 May 2022
Cited by 54 | Viewed by 4779
Abstract
There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath. The lung may be exposed to exogenous oxidative stress from cigarette smoking and indoor or [...] Read more.
There is a marked increase in oxidative stress in the lungs of patients with COPD, as measured by increased exhaled 8-isoprostane, ethane, and hydrogen peroxide in the breath. The lung may be exposed to exogenous oxidative stress from cigarette smoking and indoor or outdoor air pollution and to endogenous oxidative stress from reactive oxygen species released from activated inflammatory cells, particularly neutrophils and macrophages, in the lungs. Oxidative stress in COPD may be amplified by a reduction in endogenous antioxidants and poor intake of dietary antioxidants. Oxidative stress is a major driving mechanism of COPD through the induction of chronic inflammation, induction of cellular senescence and impaired autophagy, reduced DNA repair, increased autoimmunity, increased mucus secretion, and impaired anti-inflammatory response to corticosteroids. Oxidative stress, therefore, drives the pathology of COPD and may increase disease progression, amplify exacerbations, and increase comorbidities through systemic oxidative stress. This suggests that antioxidants may be effective as disease-modifying treatments. Unfortunately, thiol-based antioxidants, such as N-acetylcysteine, have been poorly effective, as they are inactivated by oxidative stress in the lungs, so there is a search for more effective and safer antioxidants. New antioxidants in development include mitochondria-targeted antioxidants, NOX inhibitors, and activators of the transcription factor Nrf2, which regulates several antioxidant genes. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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Other

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10 pages, 2690 KiB  
Systematic Review
Paraoxonase 1 and Chronic Obstructive Pulmonary Disease: A Meta-Analysis
by Jun Watanabe, Kazuhiko Kotani and Alejandro Gugliucci
Antioxidants 2021, 10(12), 1891; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10121891 - 26 Nov 2021
Cited by 6 | Viewed by 1434
Abstract
Oxidative stress is a driving factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). While paraoxonase 1 (PON1) is an antioxidant enzyme and a potential biomarker of this disease, data regarding the status of PON-1 in COPD are inconclusive. In this regard, [...] Read more.
Oxidative stress is a driving factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). While paraoxonase 1 (PON1) is an antioxidant enzyme and a potential biomarker of this disease, data regarding the status of PON-1 in COPD are inconclusive. In this regard, to shed light on this issue, we performed a meta-analysis of data on PON1 activity in COPD. Electronic databases (MEDLINE, Embase and CENTRAL) were searched for available studies on PON1 activity in patients with stable COPD published before October 2021. A meta-analysis was performed using random-effects models. Twelve studies (12 studies on paraoxonase and three on arylesterase) were identified. Patients with COPD had lower levels of paraoxonase activity (standard mean difference [SMD] −0.77, 95% confidence interval [CI] −1.35 to −0.18) and arylesterase activity (SMD −1.15, 95% CI −1.95 to −0.36) in comparison to healthy controls. In subgroup analyses, paraoxonase activity was lower in patients of studies as consisted of mainly non-severe COPD (SMD −1.42, 95% CI −2.04 to −0.79) and, by contrast, slightly higher in patients of studies including severe COPD (SMD 0.33, 95% CI 0.02 to 0.64) in comparison to healthy controls. Arylesterase activity showed a similar trend. Overall, PON1 activity was lower in patients with COPD, suggesting that PON1-related antioxidant defense is impaired in COPD. Future studies are warranted. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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16 pages, 3079 KiB  
Systematic Review
Glutathione Peroxidase in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis
by Elisabetta Zinellu, Angelo Zinellu, Maria Carmina Pau, Barbara Piras, Alessandro G. Fois, Sabrina Mellino, Ciriaco Carru, Arduino A. Mangoni and Pietro Pirina
Antioxidants 2021, 10(11), 1745; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111745 - 30 Oct 2021
Cited by 7 | Viewed by 1814
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Oxidative Stress in Chronic Obstructive Pulmonary Disease)
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