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      Study of oxidative stress biomarkers in chronic obstructive pulmonary disease and their correlation with disease severity in north Indian population cohort

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          Abstract

          Background:

          Oxidant-antioxidant imbalance forms a prime component in pathogenesis of chronic obstructive pulmonary disease (COPD). Studies of oxidative stress markers in South Asians were sparse.

          Methods:

          One hundred and eighty COPD patients and eighty healthy nonsmokers were enrolled in the study. Serum malondialdehyde (MDA) and iron levels were estimated for oxidative stress. Three antioxidant markers evaluated-catalase, superoxide dismutase (SOD), and serum copper. Patients on antioxidant therapy and with sepsis and chronic illness were excluded from the study.

          Results:

          The mean age of COPD patients was 59.29 ± 10.3 years. Serum levels of MDA and iron were significantly higher in COPD patients compared to controls (5.21 ± 1.9 vs. 0.71 ± 0.29 nmol MDA/ml, P = 0.0001 and 69.85 ± 85.49 vs. 79.32 ± 24.39 μg/dl, P = 0.0001, respectively). Mean level of all antioxidant enzymes catalase, SOD, and copper were significantly diminished in cases when compared to control population ( P = 0.001). Levels of MDA and iron were found to be significantly elevated in higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes (III, IV) when compared to lower GOLD Classes (I, II). The levels of serum antioxidants were significantly depleted in higher GOLD grades too. COPD patients who were male and smoked had significantly higher levels of oxidants and depleted antioxidant levels compared to female and nonsmoking compatriots. Serum MDA levels negatively correlated with forced expiratory volume 1 s and forced vital capacity ( r = −0.19 and r = −0.21, P ≤ 0.01). The presence of a cough significantly correlated with higher levels of MDA and iron ( P = 0.001). The levels of MDA negatively correlated with SOD and catalase levels.

          Conclusion:

          Oxidative markers (MDA and iron) are higher whereas antioxidants (catalase, copper, and SOD) are significantly reduced in patients of COPD. Serum MDA levels correlate with lung functions and disease severity.

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          Most cited references22

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          Antioxidants in human health and disease.

          Free radicals and antioxidants are widely discussed in the clinical and nutritional literature. Antioxidants are needed to prevent the formation and oppose the actions of reactive oxygen and nitrogen species, which are generated in vivo and cause damage to DNA, lipids, proteins, and other biomolecules. Endogenous antioxidant defenses (superoxide dismutases, H2O2-removing enzymes, metal binding proteins) are inadequate to prevent damage completely, so diet-derived antioxidants are important in maintaining health. Many dietary compounds have been suggested to be important antioxidants: The evidence for a key role of vitamins E and C is strong, but that for carotenoids and related plant pigments is weaker. Interest is also growing in the role of plant phenolics, especially flavonoids. Some antioxidants can exert prooxidant effects in vitro, but their physiological relevance is uncertain. Experimental approaches to the optimization of antioxidant nutrient intake are proposed.
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            Pathogenic triad in COPD: oxidative stress, protease–antiprotease imbalance, and inflammation

            Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction. COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma. Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression. Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology. Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease–antiprotease imbalance, and oxidative stress. Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients. For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status.
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              Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease.

              An imbalance between oxidative stress and antioxidative capacity is thought to play an important role in the development and progression of chronic obstructive pulmonary disease (COPD). To assess the lung oxidative status in patients with COPD, we studied whether exhaled hydrogen peroxide (H2O2) is increased in breath condensate of patients with stable COPD (n = 12, mean FEV1 51% pred) and in patients with exacerbated COPD (n = 19, actual FEV1 36% pred) compared with a healthy control group (n = 10, FEV1 108% pred). Expired breath condensate during 15 min of tidal breathing was collected by cooling. The concentration of H2O2 was measured spectrophotometrically by means of horse radish peroxidase-catalyzed oxidation of tetramethylbenzidine. Concentrations of H2O2 (mean +/- SEM) were significantly elevated at 0.205 +/- 0.054 microM in patients with stable COPD compared with 0.029 +/- 0.012 microM in the control group (p < 0.05) and were further increased to 0.600 +/- 0.075 microM in patients with acutely exacerbated COPD (p < 0.001 compared with patients with stable COPD). Patients with pulmonary infiltrates on chest radiograph showed similar values compared with patients without obvious infiltrates. These findings demonstrate that patients with stable COPD exhibit increased oxidant production in the airways and that oxidant production increases further during exacerbations.
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                Author and article information

                Journal
                Lung India
                Lung India
                LI
                Lung India : Official Organ of Indian Chest Society
                Medknow Publications & Media Pvt Ltd (India )
                0970-2113
                0974-598X
                Jul-Aug 2017
                : 34
                : 4
                : 324-329
                Affiliations
                [1] Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
                [1 ] Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India
                [2 ] Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
                Author notes
                Address for correspondence: Prof. Surya Kant, Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India. E-mail: jyotibajpai33@ 123456gmail.com
                Article
                LI-34-324
                10.4103/lungindia.lungindia_205_16
                5504888
                28671162
                a8ad44fb-564b-422a-a01c-9caaf11b0e13
                Copyright: © 2017 Indian Chest Society

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                Categories
                Original Article

                Respiratory medicine
                chronic obstructive pulmonary disease,malondialdehyde smoking,oxidative stress

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