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" 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.
1Università degli Studi di Milano, Dipartimento di Scienze della Salute . Pneumologia Riabilitativa Fondazione Salvatore Maugeri-Istituto Scientifico di Milano-IRCCS, Milano , Italy.
Pierachille
P
Santus
Angelo
A
Corsico
Paolo
P
Solidoro
Fulvio
F
Braido
Fabiano
F
Di Marco
Nicola
N
Scichilone
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D029481:Bronchitis, Chronic / Q000188:drug therapy; D018450:Disease Progression; D005100:Expectorants / Q000494:pharmacology / Q000627:therapeutic use*; D005541:Forced Expiratory Volume / Q000187:drug effects; D006760:Hospitalization; D006801:Humans; D008264:Macrophages; D009504:Neutrophils; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012143:Respiratory Physiological Phenomena
D000975:Antioxidants; D005100:Expectorants; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
COPD exacerbation; antioxidant; lung function; small airways