title: Pharmacological investigation on the anti-oxidant and anti-inflammatory activity of N-acetylcysteine in an ex vivo model of COPD exacerbation.
abstract: Oxidative stress is recognized to be one of predisposing factor in the pathogenesis of COPD. The oxidant/antioxidant imbalance is significantly pronounced in patients with COPD exacerbation. N-acetylcysteine (NAC) seems to be able to reduce COPD exacerbations by modulating the oxidative stress in addition to its well-known mucolytic activity, but there are discordant findings on the actual anti-oxidant activity of NAC.
  
  
  
  The anti-oxidant effect of NAC and its impact on the inflammatory response have been pharmacologically characterized on a human ex vivo model of COPD exacerbation induced by lipopolysaccharide (LPS).
  
  
  
  NAC prevented the desensitization induced by LPS incubation on the contractile tone in linear concentration-response manner. Concentrations of NAC ≥1 μM reduced the pro-oxidant response (peroxidase activity, hydrogen peroxide, malondialdehyde, nitric oxide), and improved the anti-oxidant response (total anti-oxidant capacity, glutathione, superoxide dismutase) induced by LPS. Lower concentrations of NAC (<1 μM) did not modulate the bronchial oxidative imbalance. Concentrations of NAC ≥300 μM inhibited the inflammatory response (release of IL-1β, IL-8, and TNF-α) of human airways induced by the overnight stimulation with LPS, whereas lower concentrations of NAC (≥1 μM) were sufficient to reduce the release of IL-6 elicited by LPS. Both the anti-oxidant effect and the anti-inflammatory effect of NAC were inversely correlated with the release of NKA.
  
  
  
  The findings of this study suggest that NAC may have a role in modulating the detrimental effect induced by LPS in course of COPD exacerbation. It may elicit both anti-oxidant and anti-inflammatory effects when administered at high concentrations.
authors.affiliation: Department of Systems Medicine, Chair of Respiratory Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.affiliation: Department of Systems Medicine, Chair of Respiratory Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. luigino.calzetta@uniroma2.it.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.affiliation: Regina Elena National Cancer Institute, Thoracic Surgery Unit, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
authors.affiliation: Department of Systems Medicine, Chair of Respiratory Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rogliani
authors.affiliation: Department of Experimental Medicine, Unit of Pharmacology, Second University of Naples, Naples, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000368:Aged; D000403:Airway Resistance / Q000187:drug effects / Q000276:immunology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D000111:Acetylcysteine
keywords: Anti-inflammatory effect; Anti-oxidant effect; COPD; Lipopolysaccharide; N-acetylcysteine