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Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine

The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” r...

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Autores principales: Santus, Pierachille, Corsico, Angelo, Solidoro, Paolo, Braido, Fulvio, Di Marco, Fabiano, Scichilone, Nicola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Informa Healthcare 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245155/
https://www.ncbi.nlm.nih.gov/pubmed/24787454
http://dx.doi.org/10.3109/15412555.2014.898040
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author Santus, Pierachille
Corsico, Angelo
Solidoro, Paolo
Braido, Fulvio
Di Marco, Fabiano
Scichilone, Nicola
author_facet Santus, Pierachille
Corsico, Angelo
Solidoro, Paolo
Braido, Fulvio
Di Marco, Fabiano
Scichilone, Nicola
author_sort Santus, Pierachille
collection PubMed
description The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results.
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spelling pubmed-42451552014-12-08 Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine Santus, Pierachille Corsico, Angelo Solidoro, Paolo Braido, Fulvio Di Marco, Fabiano Scichilone, Nicola COPD Review The large surface area for gas exchange makes the respiratory system particularly susceptible to oxidative stress-mediated injury. Both endogenous and exogenous pro-oxidants (e.g. cigarette smoke) trigger activation of leukocytes and host defenses. These mechanisms interact in a “multilevel cycle” responsible for the control of the oxidant/antioxidant homeostasis. Several studies have demonstrated the presence of increased oxidative stress and decreased antioxidants (e.g. reduced glutathione [GSH]) in subjects with chronic obstructive pulmonary disease (COPD), but the contribution of oxidative stress to the pathophysiology of COPD is generally only minimally discussed. The aim of this review was to provide a comprehensive overview of the role of oxidative stress in the pathogenesis of respiratory diseases, particularly COPD, and to examine the available clinical and experimental evidence on the use of the antioxidant N-acetylcysteine (NAC), a precursor of GSH, as an adjunct to standard therapy for the treatment of COPD. The proposed concept of “multilevel cycle” helps understand the relationship between respiratory diseases and oxidative stress, thus clarifying the rationale for using NAC in COPD. Until recently, antioxidant drugs such as NAC have been regarded only as mucolytic agents. Nevertheless, several clinical trials indicate that NAC may reduce the rate of COPD exacerbations and improve small airways function. The most plausible explanation for the beneficial effects observed in patients with COPD treated with NAC lies in the mucolytic and antioxidant effects of this drug. Modulation of bronchial inflammation by NAC may further account for these favorable clinical results. Informa Healthcare 2014-12 2014-04-30 /pmc/articles/PMC4245155/ /pubmed/24787454 http://dx.doi.org/10.3109/15412555.2014.898040 Text en © 2014 Informa Healthcare USA, Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.
spellingShingle Review
Santus, Pierachille
Corsico, Angelo
Solidoro, Paolo
Braido, Fulvio
Di Marco, Fabiano
Scichilone, Nicola
Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
title Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
title_full Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
title_fullStr Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
title_full_unstemmed Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
title_short Oxidative Stress and Respiratory System: Pharmacological and Clinical Reappraisal of N-Acetylcysteine
title_sort oxidative stress and respiratory system: pharmacological and clinical reappraisal of n-acetylcysteine
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245155/
https://www.ncbi.nlm.nih.gov/pubmed/24787454
http://dx.doi.org/10.3109/15412555.2014.898040
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