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Increased Oxidative Stress and Altered Levels of Nitric Oxide and Peroxynitrite in Tunisian Patients with Chronic Obstructive Pulmonary Disease: Correlation with Disease Severity and Airflow Obstruction

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Abstract

This study was aimed to evaluate the oxidant–antioxidant imbalance in the pathogenesis of chronic obstructive pulmonary disease (COPD) in Tunisians. We assessed 16 parameters related to the oxidative status that include malondialdehyde (MDA), total protein carbonyls (PCs), and advanced oxidation protein products (AOPP). We also examined the activity of glutathione peroxydase (GSH-Px), catalase, and superoxide dismutase (SOD) in the plasma and erythrocytes. Levels of total thiols, reduced glutathione (GSH), total antioxidant status (TAS), hydrogen peroxide, ascorbic acid, iron, and protein sulfhydryls were determined using spectrophotometry. We also evaluated the level of nitric oxide (NO) and peroxynitrite in plasma from COPD patients and healthy controls. Estimation of DNA damage was determined using the comet assay. Pulmonary functional tests were performed by body plethysmography. Levels of MDA, PC, DNA damage, and AOPP were significantly increased while total thiols, GSH, and TAS were decreased in COPD patients. GSH-Px activity was higher in COPD patients while no difference was found for catalase and SOD. We also observed a lower level of NO and peroxynitrite in COPD patients. Decreased levels of peroxynitrite were found to correlate with disease progression, as well as with forced expiratory volume in 1 s/forced vital capacity among COPD patients. Multivariate analysis revealed that NO is associated with pathological pathways that help to predict patient outcome independently of the degree of airflow obstruction. These results indicate the presence of a systemic oxidative stress and highlight the importance of NO and peroxynitrite as major effectors in COPD development and airflow obstruction.

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Abbreviations

AOPP:

Advanced oxidation protein products

BMI:

Body mass index

CAT:

Catalase

COPD:

Chronic obstructive pulmonary disease

FEV1%:

Forced expiratory volume in 1 s (%predicted)

FVC:

Forced vital capacity

GOLD:

Global Initiative for Chronic Obstructive Lung Disease

GSH:

Glutathione

GSH-Px:

Glutathione peroxydase

MDA:

Malondialdehyde

NO:

Nitric oxide

PC:

Protein carbonyls

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TAS:

Total antioxidant status

TBA:

Thiobarbituric acid

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Acknowledgments

This work was supported by the Ministry of Higher Education and Scientific Research and by the Ministry of Public Health of the Tunisian Government. We would like to thank Pr Saloua Abid (Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir University, Tunisia) and Dr Ghada ben Salah (Laboratory of Human Molecular Genetics, Faculty of Médicine, Sfax, Tunisia) for their help in the realization of the comet test.

Conflict of interest

The authors declare that they have no competing interests.

Author’s contributions

BAA (PhD) carried out the different experiments and drafted the manuscript; FH (Associate Professor), BNH (Assistant, PhD), CE (MD, PhD), BS (thesis student), and CH (thesis student) participated in the measurement of the different parameters related to the oxidant–antioxidant status; YS (MD, Professor), GA (MD, Professor), BM (MD, Professor), and TZ (MD, PhD, Professor) participated in the design of the study and coordination and helped to draft the manuscript; CK (PhD, Professor) participated in the different experiments, in the design of the study and to draft the manuscript. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Unité de recherche UR12ES06, Physiologie de l’Exercice et Physiopathologie: de l’Intégré au Moléculaire « Biologie, Médecine et Santé », Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia

    Amel ben Anes, Sarra Bchir, Hela ben Nasr, Zouhair Tabka & Karim Chahed

  2. Unité de Recherche de Toxicologie-Microbiologie Environnementale et Santé (UR/11 ES70), Faculté des Sciences de Sfax, Sfax, Tunisia

    Hamadi Fetoui

  3. Unité de Recherche 03/UR/09-01 «Génome, Diagnostic Immunitaire et valorisation», Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia

    Hassiba Chahdoura

  4. Unité de Recherche 04/UR/08-05 Molecular Immunogenetics, Faculté de Médecine, Sousse, Tunisia

    Elyes Chabchoub

  5. Unité de Recherche « UR06SP05 » Centre Régional de Transfusion Sanguine, CHU Farhat Hached, Sousse, Tunisia

    Saloua Yacoub

  6. Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia

    Abdelhamid Garrouch & Mohamed Benzarti

  7. Faculté des Sciences de Sfax, Sfax, Tunisia

    Karim Chahed

Authors
  1. Amel ben Anes
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  2. Hamadi Fetoui
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  3. Sarra Bchir
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  5. Hassiba Chahdoura
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  6. Elyes Chabchoub
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  7. Saloua Yacoub
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  8. Abdelhamid Garrouch
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  10. Zouhair Tabka
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  11. Karim Chahed
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Corresponding author

Correspondence to Karim Chahed.

Additional information

Summary at a Glance: This study provides a strong evidence for altered oxidant–antioxidant balance in the plasma from Tunisian patients with COPD. Our findings also point out the relevance of nitric oxide and peroxynitrite as major effectors in COPD development and airflow obstruction.

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ben Anes, A., Fetoui, H., Bchir, S. et al. Increased Oxidative Stress and Altered Levels of Nitric Oxide and Peroxynitrite in Tunisian Patients with Chronic Obstructive Pulmonary Disease: Correlation with Disease Severity and Airflow Obstruction. Biol Trace Elem Res 161, 20–31 (2014). https://doi.org/10.1007/s12011-014-0087-4

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  • DOI: https://doi.org/10.1007/s12011-014-0087-4

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