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      The effect of conjugated linoleic acid on oxidative stress and matrix metalloproteinases 2 and 9 in patients with COPD

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          Abstract

          Background

          Natural antioxidants in foods may be used in prevention and treatment of oxidative stress and inflammation in COPD. Therefore, this study aimed to evaluate the effect of conjugated linoleic acid (CLA) supplement as natural antioxidants on oxidative stress levels, and MMP2 and MMP9 serum levels in COPD patients.

          Materials and methods

          This clinical trial study was conducted on 90 (supplement group=45 and control group=45) COPD patients in Ardabil city, Iran, in 2015. After obtaining written consent, general information was collected from each patient using a validated and reliable questionnaire. Supplement group received 3.2 g of CLA and those in the control group were given 3.2 g of placebo for 6 weeks on a daily basis. Fasting blood samples were taken from all of the patients for testing of malondialdehyde (MDA), MMP2, and MMP9 levels at the beginning and end of the study. Data were analyzed using Kolmogorov–Smirnov test, independent samples t-test, paired sample t-test, chi-square test, and ANOVA.

          Results

          There were no significant differences between the two groups with regard to mean age, smoking status, and serum level of MDA at the beginning of the study. In the supplement group, the serum level of MDA decreased significantly at the end of the 6th week compared to that in the beginning of the study ( p=0.0004), while in the placebo group, the difference was found to be insignificant. The serum level of MMP9 decreased significantly in the supplement group, while in the placebo group its level increased significantly as compared to that at the beginning of the study ( p<0.05). The serum levels of MMP2 indicated no significant differences between the two groups neither at the beginning nor at the end of the study.

          Conclusion

          These findings indicated that CLA supplementation may be helpful for COPD patients through inhibiting the production of oxidative stress and controlling MMP9 serum levels.

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          Most cited references 28

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          Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy.

          Asthma and chronic obstructive pulmonary disease (COPD) are inflammatory lung diseases that are characterized by systemic and chronic localized inflammation and oxidative stress. Sources of oxidative stress arise from the increased burden of inhaled oxidants, as well as elevated amounts of reactive oxygen species (ROS) released from inflammatory cells. Increased levels of ROS, either directly or via the formation of lipid peroxidation products, may play a role in enhancing the inflammatory response in both asthma and COPD. Moreover, in COPD it is now recognized as the main pathogenic factor for driving disease progression and increasing severity. ROS and lipid peroxidation products can influence the inflammatory response at many levels through its impact on signal transduction mechanisms, activation of redox-sensitive transcriptions factors, and chromatin regulation resulting in pro-inflammatory gene expression. It is this impact of ROS on chromatin regulation by reducing the activity of the transcriptional co-repressor, histone deacetylase-2 (HDAC-2), that leads to the poor efficacy of corticosteroids in COPD, severe asthma, and smoking asthmatics. Thus, the presence of oxidative stress has important consequences for the pathogenesis, severity, and treatment of asthma and COPD. However, for ROS to have such an impact, it must first overcome a variety of antioxidant defenses. It is likely, therefore, that a combination of antioxidants may be effective in the treatment of asthma and COPD. Various approaches to enhance the lung antioxidant screen and clinical trials of antioxidant compounds are discussed.
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            Series "matrix metalloproteinases in lung health and disease": Matrix metalloproteinases in COPD.

            There is considerable evidence that matrix metalloproteinases (MMPs) are up- and/or downregulated in chronic obstructive pulmonary disease (COPD), particularly in emphysema, in which they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD. In cigarette smoke-induced animal models of emphysema, MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs, evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodelling, smoke-induced pulmonary hypertension and chronic bronchitis, but MMP-12 participates in experimental small airway modelling. To date, the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodelling, but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.
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              Hydroxyl Radical and Its Scavengers in Health and Disease

              It is generally believed that diseases caused by oxidative stress should be treated with antioxidants. However, clinical trials with such antioxidants as ascorbic acid and vitamin E, failed to produce the expected beneficial results. On the other hand, important biomolecules can be modified by the introduction of oxygen atoms by means of non-oxidative hydroxyl radicals. In addition, hydroxyl radicals can reduce disulfide bonds in proteins, specifically fibrinogen, resulting in their unfolding and scrambled refolding into abnormal spatial configurations. Consequences of this reaction are observed in many diseases such as atherosclerosis, cancer and neurological disorders, and can be prevented by the action of non-reducing substances. Moreover, many therapeutic substances, traditionally classified as antioxidants, accept electrons and thus are effective oxidants. It is described in this paper that hydroxyl radicals can be generated by ferric ions without any oxidizing agent. In view of the well-known damaging effect of poorly chelated iron in the human body, numerous natural products containing iron binding agents can be essential in the maintenance of human health. However, beneficial effects of the great number of phytochemicals that are endowed with hydroxyl radical scavenging and/or iron chelating activities should not be considered as a proof for oxidative stress.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2018
                03 May 2018
                : 13
                : 1449-1454
                Affiliations
                [1 ]Department of Internal Medicine, Emam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran
                [2 ]Biochemistry and Nutrition Department, Ardabil University of Medical Sciences, Ardabil, Iran
                [3 ]Department of Internal Medicine (Pulmonary Division), Emam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran
                [4 ]Department of Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
                Author notes
                Correspondence: Ali Nemati, Biochemistry and Nutrition Department, Ardabil University of Medical Sciences, Daneshgah Street, Ardabil, Iran, Tel +98 45 3351 0052, Fax +98 45 3351 3776, Email ali.nemati@ 123456arums.ac.ir
                Article
                copd-13-1449
                10.2147/COPD.S155985
                5939916
                © 2018 Matin et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Clinical Trial Report

                Respiratory medicine

                mmp2, mmp9, oxidative stress, copd, cla

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