Pharmacological investigation on the anti-oxidant and anti-inflammatory activity of N-acetylcysteine in an ex vivo model of COPD exacerbation

M. Cazzola, L. Calzetta, F. Facciolo, P. Rogliani, M. G. Matera

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: 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. METHODS: 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). RESULTS: NAC prevented the desensitization induced by LPS incubation on the contractile tone in linear concentration-response manner. Concentrations of NAC >/=1 muM 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 (/=300 muM inhibited the inflammatory response (release of IL-1beta, IL-8, and TNF-alpha) of human airways induced by the overnight stimulation with LPS, whereas lower concentrations of NAC (>/=1 muM) 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. CONCLUSIONS: 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.
Original languageEnglish
Pages (from-to)26
JournalRespiratory Research
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 24 2017

Keywords

  • Anti-inflammatory effect
  • Anti-oxidant effect
  • COPD
  • Lipopolysaccharide
  • N-acetylcysteine

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