Antioxidants

Research

15 pages, 2306 KiB

Open AccessEditor’s ChoiceArticle

Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice

by Guodong Zhou, Weiwu Jiang, Guobin Xia, Lihua Wang, Molly Richardson, Chun Chu and Bhagavatula Moorthy

Antioxidants 2022, 11(1), 119; https://doi.org/10.3390/antiox11010119 - 5 Jan 2022

Cited by 8 | Viewed by 2512

Abstract

Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of [...] Read more.

Numerous human and animal studies have reported positive correlation between carcinogen-DNA adduct levels and cancer occurrence. Therefore, attenuation of DNA adduct levels would be expected to suppress tumorigenesis. In this investigation, we report that the antioxidants omega 3-fatty acids, which are constituents of fish oil (FO), significantly decreased DNA adduct formation by polycyclic aromatic hydrocarbons (PAHs). B6C3F1 male mice were fed an FO or corn oil (CO) diet, or A/J male mice were pre-fed with omega-3 fatty acids eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA). While the B6C3F1 mice were administered two doses of a mixture of seven carcinogenic PAHs including benzo(a)pyrene (BP), the A/J mice were treated i.p. with pure benzo[a]pyrene (BP). Animals were euthanized after 1, 3, or 7 d after PAH treatment. DNA adduct levels were measured by the ³²P-postlabeling assay. Our results showed that DNA adduct levels in the lungs of mice 7 d after treatment were significantly decreased in the FO or EPA/DHA groups compared with the CO group. Interestingly, both qPCR and Western blot analyses revealed that FO, DHA and EPA/DHA significantly decreased the expression of cytochrome P450 (CYP) 1B1. CYP1B1 plays a critical role in the metabolic activation of BP to DNA-reactive metabolites. qPCR also showed that the expression of some metabolic and DNA repair genes was induced by BP and inhibited by FO or omega-3 fatty acids in liver, but not lung. Our results suggest that a combination of mechanism entailing CYP1B1 inhibition and the modulation of DNA repair genes contribute to the attenuation of PAH-mediated carcinogenesis by omega 3 fatty acids. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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24 pages, 4431 KiB

Open AccessArticle

Transcriptomics Underlying Pulmonary Ozone Pathogenesis Regulated by Inflammatory Mediators in Mice

by Hye-Youn Cho, Anne E. Jedlicka, Frederick H. Chang, Jacqui Marzec, Alison K. Bauer and Steven R. Kleeberger

Antioxidants 2021, 10(9), 1489; https://doi.org/10.3390/antiox10091489 - 18 Sep 2021

Cited by 6 | Viewed by 2840

Abstract

Ozone (O₃) is the predominant oxidant air pollutant associated with airway inflammation, lung dysfunction, and the worsening of preexisting respiratory diseases. We previously demonstrated the injurious roles of pulmonary immune receptors, tumor necrosis factor receptor (TNFR), and toll-like receptor 4, as [...] Read more.

Ozone (O₃) is the predominant oxidant air pollutant associated with airway inflammation, lung dysfunction, and the worsening of preexisting respiratory diseases. We previously demonstrated the injurious roles of pulmonary immune receptors, tumor necrosis factor receptor (TNFR), and toll-like receptor 4, as well as a transcription factor NF-κB, in response to O₃ in mice. In the current study, we profiled time-dependent and TNFR- and NF-κB-regulated lung transcriptome changes by subacute O₃ to illuminate the underlying molecular events and downstream targets. Mice lacking Tnfr1/Tnfr2 (Tnfr^-/-) or Nfkb1 (Nfkb1^-/-) were exposed to air or O₃. Lung RNAs were prepared for cDNA microarray analyses, and downstream and upstream mechanisms were predicted by pathway analyses of the enriched genes. O₃ significantly altered the genes involved in inflammation and redox (24 h), cholesterol biosynthesis and vaso-occlusion (48 h), and cell cycle and DNA repair (48–72 h). Transforming growth factor-β1 was a predicted upstream regulator. Lack of Tnfr suppressed the immune cell proliferation and lipid-related processes and heightened epithelial cell integrity, and Nfkb1 deficiency markedly suppressed lung cell cycle progress during O₃ exposure. Common differentially regulated genes by TNFR and NF-κB1 (e.g., Casp8, Il6, and Edn1) were predicted to protect the lungs from cell death, connective tissue injury, and inflammation. Il6-deficient mice were susceptible to O₃-induced protein hyperpermeability, indicating its defensive role, while Tnf-deficient mice were resistant to overall lung injury caused by O₃. The results elucidated transcriptome dynamics and provided new insights into the molecular mechanisms regulated by TNFR and NF-κB1 in pulmonary subacute O₃ pathogenesis. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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19 pages, 3939 KiB

Open AccessArticle

Intermittent Hypoxia-Hyperoxia and Oxidative Stress in Developing Human Airway Smooth Muscle

by Colleen M. Bartman, Daniel Wasim Awari, Christina M. Pabelick and Y. S. Prakash

Antioxidants 2021, 10(9), 1400; https://doi.org/10.3390/antiox10091400 - 31 Aug 2021

Cited by 8 | Viewed by 2795

Abstract

Premature infants are frequently and intermittently administered supplemental oxygen during hypoxic episodes, resulting in cycles of intermittent hypoxia and hyperoxia. The relatively hypoxic in utero environment is important for lung development while hyperoxia during the neonatal period is recognized as detrimental towards the [...] Read more.

Premature infants are frequently and intermittently administered supplemental oxygen during hypoxic episodes, resulting in cycles of intermittent hypoxia and hyperoxia. The relatively hypoxic in utero environment is important for lung development while hyperoxia during the neonatal period is recognized as detrimental towards the development of diseases such as bronchopulmonary dysplasia and bronchial asthma. Understanding early mechanisms that link hypoxic, hyperoxic, and intermittent hypoxic-hyperoxic exposures to altered airway structure and function are key to developing advanced therapeutic approaches in the clinic. Changes in oxygen availability can be detrimental to cellular function and contribute to oxidative damage. Here, we sought to determine the effect of oxygen on mitochondria in human fetal airway smooth muscle cells exposed to either 5% O₂, 21% O₂, 40% O₂, or cycles of 5% and 40% O₂ (intermittent hypoxia-hyperoxia). Reactive oxygen species production, altered mitochondrial morphology, and changes in mitochondrial respiration were assessed in the context of the antioxidant N-acetylcysteine. Our findings show developing airway smooth muscle is differentially responsive to hypoxic, hyperoxic, or intermittent hypoxic-hyperoxic exposure in terms of mitochondrial structure and function. Cycling O₂ decreased mitochondrial branching and branch length similar to hypoxia and hyperoxia in the presence of antioxidants. Additionally, hypoxia decreased overall mitochondrial respiration while the addition of antioxidants increased respiration in normoxic and O₂-cycling conditions. These studies show the necessity of balancing oxidative damage and antioxidant defense systems in the developing airway. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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10 pages, 984 KiB

Open AccessArticle

Alveolar Nitric Oxide as a Biomarker of COVID-19 Lung Sequelae: A Pivotal Study

by Paolo Cameli, Elena Bargagli, Laura Bergantini, Miriana d’Alessandro, Bruna Giugno, Francesco Gentili and Piersante Sestini

Antioxidants 2021, 10(9), 1350; https://doi.org/10.3390/antiox10091350 - 25 Aug 2021

Cited by 14 | Viewed by 2885

Abstract

Since SARS-CoV-2 emerged in 2019, strict monitoring of post-COVID-19 patients in order to ensure the early detection of sequelae and/or chronic organ damage that could been associated with the infection has been essential. Potential involvement of the NO pathway in the development of [...] Read more.

Since SARS-CoV-2 emerged in 2019, strict monitoring of post-COVID-19 patients in order to ensure the early detection of sequelae and/or chronic organ damage that could been associated with the infection has been essential. Potential involvement of the NO pathway in the development of post-COVID-19 lung fibrotic alterations is feasible, since the majority of respiratory cells can produce NO, and fractional exhaled NO (FeNO) represents a biomarker of airway inflammation. The aim of this study was to investigate the potential utility of multiple-flow FeNO parameters in a post-COVID-19 population and to compare it with other indicators of lung damage proposed in the literature. We enrolled 20 patients hospitalized for COVID-19, who underwent clinical, respiratory functional (including PFTs and FeNO) and radiological follow-up after discharge. Compared with age- and sex-matched healthy controls, post-COVID-19 patients showed significantly higher FeNO 350 mL/s and CaNO levels. Moreover, among the parameters included in the follow-up, CaNO showed the best accuracy in indicating predominant fibrotic changes and GGO at CT scan. To our knowledge, this preliminary study has investigated for the first time multiple-flow FeNO parameters in a post-COVID-19 population. The evidence of increased CaNO values may imply the persistence of alveolar and bronchiolar inflammation and/or a mild impairment of the alveolar-capillary membrane in these patients. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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13 pages, 3914 KiB

Open AccessArticle

Neonatal Extracellular Superoxide Dismutase Knockout Mice Increase Total Superoxide Dismutase Activity and VEGF Expression after Chronic Hyperoxia

by Maxwell Mathias, Joann Taylor, Elizabeth Mendralla and Marta Perez

Antioxidants 2021, 10(8), 1236; https://doi.org/10.3390/antiox10081236 - 1 Aug 2021

Cited by 4 | Viewed by 2699

Abstract

Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor [...] Read more.

Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor (VEGF) and nitric oxide (NO) signaling in vascular endothelium. We utilized a mouse model of neonatal hyperoxic lung injury and SOD3 knockout (KO) mice to evaluate its function during chronic hyperoxia exposure. Wild-type age-matched neonatal C57Bl/6 (WT) and SOD3^−/− (KO) mice were placed in normoxia (21% FiO₂, RA) or chronic hyperoxia (75% FiO₂, O₂) within 24 h of birth for 14 days continuously and then euthanized. Lungs were harvested for histologic evaluation, as well as comparison of antioxidant enzyme expression, SOD activity, VEGF expression, and portions of the NO signaling pathway. Surprisingly, KO-O₂ mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O₂ mice. KO-O₂ mice had increased total SOD activity and increased VEGF expression when compared to WT-O₂ mice. No genotype differences were noted in intracellular antioxidant enzyme expression or the NO signaling pathway. These results demonstrate that SOD3 KO mice can survive prolonged hyperoxia without exacerbation of alveolar or vascular phenotype. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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14 pages, 4727 KiB

Open AccessArticle

Aesculetin Inhibits Airway Thickening and Mucus Overproduction Induced by Urban Particulate Matter through Blocking Inflammation and Oxidative Stress Involving TLR4 and EGFR

by Su-Yeon Oh, Yun-Ho Kim, Min-Kyung Kang, Eun-Jung Lee, Dong-Yeon Kim, Hyeongjoo Oh, Soo-Il Kim, Woojin Na, Il-Jun Kang and Young-Hee Kang

Antioxidants 2021, 10(3), 494; https://doi.org/10.3390/antiox10030494 - 22 Mar 2021

Cited by 10 | Viewed by 3293

Abstract

Particulate matter (PM) is a mixture of solid and liquid air pollutant particles suspended in the air, varying in composition, size, and physical features. PM is the most harmful form of air pollution due to its ability to penetrate deep into the lungs [...] Read more.

Particulate matter (PM) is a mixture of solid and liquid air pollutant particles suspended in the air, varying in composition, size, and physical features. PM is the most harmful form of air pollution due to its ability to penetrate deep into the lungs and blood streams, causing diverse respiratory diseases. Aesculetin, a coumarin derivative present in the Sancho tree and chicory, is known to have antioxidant and anti-inflammatory effects in the vascular and immune system. However, its effect on PM-induced airway thickening and mucus hypersecretion is poorly understood. The current study examined whether naturally-occurring aesculetin inhibited airway thickening and mucus hypersecretion caused by urban PM₁₀ (uPM₁₀, particles less than 10 μm). Mice were orally administrated with 10 mg/kg aesculetin and exposed to 6 μg/mL uPM₁₀ for 8 weeks. To further explore the mechanism(s) involved in inhibition of uPM₁₀-induced mucus hypersecretion by aesculetin, bronchial epithelial BEAS-2B cells were treated with 1–20 µM aesculetin in the presence of 2 μg/mL uPM₁₀. Oral administration of aesculetin attenuated collagen accumulation and mucus hypersecretion in the small airways inflamed by uPM₁₀. In addition, aesculetin inhibited uPM₁₀-evoked inflammation and oxidant production in lung tissues. Further, aesculetin accompanied the inhibition of induction of bronchial epithelial toll-like receptor 4 (TLR4) and epidermal growth factor receptor (EFGR) elevated by uPM₁₀. The inhibition of TLR4 and EGFR accompanied bronchial mucus hypersecretion in the presence of uPM₁₀. Oxidative stress was responsible for the epithelial induction of TLR4 and EGFR, which was disrupted by aesculetin. These results demonstrated that aesculetin ameliorated airway thickening and mucus hypersecretion by uPM₁₀ inhalation by inhibiting pulmonary inflammation via oxidative stress-stimulated TLR4 and EGFR. Therefore, aesculetin may be a promising agent for treating airway mucosa-associated disorders elicited by urban coarse particulates. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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22 pages, 6266 KiB

Open AccessFeature PaperArticle

Design and Comprehensive Characterization of Tetramethylpyrazine (TMP) for Targeted Lung Delivery as Inhalation Aerosols in Pulmonary Hypertension (PH): In Vitro Human Lung Cell Culture and In Vivo Efficacy

by Priya Muralidharan, Maria F. Acosta, Alexan I. Gomez, Carissa Grijalva, Haiyang Tang, Jason X.-J. Yuan and Heidi M. Mansour

Antioxidants 2021, 10(3), 427; https://doi.org/10.3390/antiox10030427 - 11 Mar 2021

Cited by 14 | Viewed by 3524

Abstract

This is the first study reporting on the design and development innovative inhaled formulations of the novel natural product antioxidant therapeutic, tetramethylpyrazine (TMP), also known as ligustrazine. TMP is obtained from Chinese herbs belonging to the class of Ligusticum. It is known [...] Read more.

This is the first study reporting on the design and development innovative inhaled formulations of the novel natural product antioxidant therapeutic, tetramethylpyrazine (TMP), also known as ligustrazine. TMP is obtained from Chinese herbs belonging to the class of Ligusticum. It is known to have antioxidant properties. It can act as a Nrf2/ARE activator and a Rho/ROCK inhibitor. The present study reports for the first time on the comprehensive characterization of raw TMP (non-spray dried) and spray dried TMP in a systematic manner using thermal analysis, electron microscopy, optical microscopy, and Raman spectroscopy. The in vitro aerosol dispersion performance of spray dried TMP was tested using three different FDA-approved unit-dose capsule-based human dry powder inhaler devices. In vitro human cellular studies were conducted on pulmonary cells from different regions of the human lung to examine the biocompatibility and non-cytotoxicity of TMP. Furthermore, the efficacy of inhaled TMP as both liquid and dry powder inhalation aerosols was tested in vivo using the monocrotaline (MCT)-induced PH rat model. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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19 pages, 2804 KiB

Open AccessArticle

The Positive Allosteric Modulation of alpha7-Nicotinic Cholinergic Receptors by GAT107 Increases Bacterial Lung Clearance in Hyperoxic Mice by Decreasing Oxidative Stress in Macrophages

by Alex G. Gauthier, Jiaqi Wu, Mosi Lin, Ravikumar Sitapara, Abhijit Kulkarni, Ganesh A. Thakur, Edward E. Schmidt, Jeanette C. Perron, Charles R. Ashby, Jr. and Lin L. Mantell

Antioxidants 2021, 10(1), 135; https://doi.org/10.3390/antiox10010135 - 19 Jan 2021

Cited by 7 | Viewed by 3235

Abstract

Supplemental oxygen therapy with supraphysiological concentrations of oxygen (hyperoxia; >21% O₂) is a life-saving intervention for patients experiencing respiratory distress. However, prolonged exposure to hyperoxia can compromise bacterial clearance processes, due to oxidative stress-mediated impairment of macrophages, contributing to the increased [...] Read more.

Supplemental oxygen therapy with supraphysiological concentrations of oxygen (hyperoxia; >21% O₂) is a life-saving intervention for patients experiencing respiratory distress. However, prolonged exposure to hyperoxia can compromise bacterial clearance processes, due to oxidative stress-mediated impairment of macrophages, contributing to the increased susceptibility to pulmonary infections. This study reports that the activation of the α7 nicotinic acetylcholine receptor (α7nAChR) with the delete allosteric agonistic-positive allosteric modulator, GAT107, decreases the bacterial burden in mouse lungs by improving hyperoxia-induced lung redox imbalance. The incubation of RAW 264.7 cells with GAT107 (3.3 µM) rescues hyperoxia-compromised phagocytic functions in cultured macrophages, RAW 264.7 cells, and primary bone marrow-derived macrophages. Similarly, GAT107 (3.3 µM) also attenuated oxidative stress in hyperoxia-exposed macrophages, which prevents oxidation and hyper-polymerization of phagosome filamentous actin (F-actin) from oxidation. Furthermore, GAT107 (3.3 µM) increases the (1) activity of superoxide dismutase 1; (2) activation of Nrf2 and (3) the expression of heme oxygenase-1 (HO-1) in macrophages exposed to hyperoxia. Overall, these data suggest that the novel α7nAChR compound, GAT107, could be used to improve host defense functions in patients, such as those with COVID-19, who are exposed to prolonged periods of hyperoxia. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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Review

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14 pages, 605 KiB

Open AccessReview

Metabolism, Mitochondrial Dysfunction, and Redox Homeostasis in Pulmonary Hypertension

by Daniel Colon Hidalgo, Hanan Elajaili, Hagir Suliman, Marjorie Patricia George, Cassidy Delaney and Eva Nozik

Antioxidants 2022, 11(2), 428; https://doi.org/10.3390/antiox11020428 - 21 Feb 2022

Cited by 17 | Viewed by 3687

Abstract

Pulmonary hypertension (PH) represents a group of disorders characterized by elevated mean pulmonary artery (PA) pressure, progressive right ventricular failure, and often death. Some of the hallmarks of pulmonary hypertension include endothelial dysfunction, intimal and medial proliferation, vasoconstriction, inflammatory infiltration, and in situ [...] Read more.

Pulmonary hypertension (PH) represents a group of disorders characterized by elevated mean pulmonary artery (PA) pressure, progressive right ventricular failure, and often death. Some of the hallmarks of pulmonary hypertension include endothelial dysfunction, intimal and medial proliferation, vasoconstriction, inflammatory infiltration, and in situ thrombosis. The vascular remodeling seen in pulmonary hypertension has been previously linked to the hyperproliferation of PA smooth muscle cells. This excess proliferation of PA smooth muscle cells has recently been associated with changes in metabolism and mitochondrial biology, including changes in glycolysis, redox homeostasis, and mitochondrial quality control. In this review, we summarize the molecular mechanisms that have been reported to contribute to mitochondrial dysfunction, metabolic changes, and redox biology in PH. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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14 pages, 822 KiB

Open AccessReview

Friend or Foe? The Roles of Antioxidants in Acute Lung Injury

by Yang Liu, Shujun Zhou, Du Xiang, Lingao Ju, Dexin Shen, Xinghuan Wang and Yanfeng Wang

Antioxidants 2021, 10(12), 1956; https://doi.org/10.3390/antiox10121956 - 7 Dec 2021

Cited by 18 | Viewed by 3817

Abstract

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency caused by various intra- and extra-pulmonary injury factors. The oxidative stress caused by excessive reactive oxygen species (ROS) produced in the lungs plays an important role in the pathogenesis of ALI. ROS is [...] Read more.

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency caused by various intra- and extra-pulmonary injury factors. The oxidative stress caused by excessive reactive oxygen species (ROS) produced in the lungs plays an important role in the pathogenesis of ALI. ROS is a “double-edged sword”, which is widely involved in signal transduction and the life process of cells at a physiological concentration. However, excessive ROS can cause mitochondrial oxidative stress, leading to the occurrence of various diseases. It is well-known that antioxidants can alleviate ALI by scavenging ROS. Nevertheless, more and more studies found that antioxidants have no significant effect on severe organ injury, and may even aggravate organ injury and reduce the survival rate of patients. Our study introduces the application of antioxidants in ALI, and explore the mechanisms of antioxidants failure in various diseases including it. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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26 pages, 1621 KiB

Open AccessReview

Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD

by Brandon W. Lewis, Maria L. Ford, Lynette K. Rogers and Rodney D. Britt, Jr.

Antioxidants 2021, 10(9), 1335; https://doi.org/10.3390/antiox10091335 - 24 Aug 2021

Cited by 34 | Viewed by 5225

Abstract

Corticosteroid insensitivity is a key characteristic of patients with severe asthma and COPD. These individuals experience greater pulmonary oxidative stress and inflammation, which contribute to diminished lung function and frequent exacerbations despite the often and prolonged use of systemic, high dose corticosteroids. Reactive [...] Read more.

Corticosteroid insensitivity is a key characteristic of patients with severe asthma and COPD. These individuals experience greater pulmonary oxidative stress and inflammation, which contribute to diminished lung function and frequent exacerbations despite the often and prolonged use of systemic, high dose corticosteroids. Reactive oxygen and nitrogen species (RONS) promote corticosteroid insensitivity by disrupting glucocorticoid receptor (GR) signaling, leading to the sustained activation of pro-inflammatory pathways in immune and airway structural cells. Studies in asthma and COPD models suggest that corticosteroids need a balanced redox environment to be effective and to reduce airway inflammation. In this review, we discuss how oxidative stress contributes to corticosteroid insensitivity and the importance of optimizing endogenous antioxidant responses to enhance corticosteroid sensitivity. Future studies should aim to identify how antioxidant-based therapies can complement corticosteroids to reduce the need for prolonged high dose regimens in patients with severe asthma and COPD. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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18 pages, 834 KiB

Open AccessReview

Tocotrienols: Dietary Supplements for Chronic Obstructive Pulmonary Disease

by Xiangming Ji, Hongwei Yao, Maureen Meister, Douglas S. Gardenhire and Huanbiao Mo

Antioxidants 2021, 10(6), 883; https://doi.org/10.3390/antiox10060883 - 31 May 2021

Cited by 11 | Viewed by 6326

Abstract

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Emphysema and chronic bronchitis are the two major phenotypes of COPD, which have many symptoms, such as dyspnea, chronic cough, and mucus overproduction. Emphysema is characterized by the destruction [...] Read more.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Emphysema and chronic bronchitis are the two major phenotypes of COPD, which have many symptoms, such as dyspnea, chronic cough, and mucus overproduction. Emphysema is characterized by the destruction of the alveolar wall, while chronic bronchitis is characterized by limitations in expiratory airflow. Cigarette smoking is the most significant risk factor for the pathogenesis of COPD in the developed world. Chronic inflammation contributes to the onset and progression of the disease and furthers the risk of comorbidities. Current treatment options and prevention strategies for COPD are very limited. Tocotrienols are a group of vitamin E molecules with antioxidant and anti-inflammatory properties. Individual tocotrienols (α, γ, and δ) have shown their ability to attenuate inflammation specifically via suppressing nuclear factor-κB-mediated cytokine production. The δ- and γ-forms of tocotrienols have been indicated as the most effective in the prevention of macrophage infiltration, production of reactive oxygen species, and cytokine secretion. This review briefly discusses the pathogenesis of COPD and the role of inflammation therein. Furthermore, we summarize the in vitro and in vivo evidence for the anti-inflammatory activity of tocotrienols and their potential application to COPD management. Coupled with the bioavailability and safety profile of tocotrienols, the ability of these compounds to modulate COPD progression by targeting the inflammation pathways renders them potential candidates for novel therapeutic approaches in the treatment of COPD patients. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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Other

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18 pages, 6608 KiB

Open AccessSystematic Review

Circulating Malondialdehyde Concentrations in Obstructive Sleep Apnea (OSA): A Systematic Review and Meta-Analysis with Meta-Regression

by Maria Carmina Pau, Elisabetta Zinellu, Sara S. Fois, Barbara Piras, Gianfranco Pintus, Ciriaco Carru, Arduino A. Mangoni, Alessandro G. Fois, Angelo Zinellu and Pietro Pirina

Antioxidants 2021, 10(7), 1053; https://doi.org/10.3390/antiox10071053 - 29 Jun 2021

Cited by 15 | Viewed by 2590

Abstract

Oxidative stress induced by nocturnal intermittent hypoxia plays a significant pathophysiological role in obstructive sleep apnea (OSA). Malondialdehyde (MDA), one of the most commonly investigated markers of lipid peroxidation, might assist with the monitoring of oxidative balance in OSA. We conducted a systematic [...] Read more.

Oxidative stress induced by nocturnal intermittent hypoxia plays a significant pathophysiological role in obstructive sleep apnea (OSA). Malondialdehyde (MDA), one of the most commonly investigated markers of lipid peroxidation, might assist with the monitoring of oxidative balance in OSA. We conducted a systematic review and meta-analysis to evaluate the differences in circulating MDA concentrations between patients with OSA and non-OSA controls. A systematic search was conducted in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar from inception to December 2020 by using the following terms: “malondialdehyde” or “MDA”; and “Obstructive Sleep Apnea Syndrome”, “OSAS” or “OSA”. We identified 26 studies in 1223 OSA patients and 716 controls. The pooled MDA concentrations were significantly higher in patients with OSA (standardized mean difference (SMD) 1.43 μmol/L, 95% confidence interval (CI) 1.03 to 1.83 μmol/L, p < 0.001). There was extreme heterogeneity between the studies (I² = 92.3%, p < 0.001). In meta-regression analysis, the SMD was significantly associated with age, the assay type used and publication year. In our meta-analysis, MDA concentrations were significantly higher in OSA patients than in controls. This finding suggests that MDA, which is a marker of lipid peroxidation, is involved in the pathogenesis of OSA and provides insights for future studies investigating its potential clinical use. Full article

(This article belongs to the Special Issue Antioxidants and Lung Diseases)

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