RT Journal Article SR Electronic T1 Pharmacological characterization of the anti-oxidant activity of N-acetylcysteine in an ex vivo model of COPD exacerbation JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP PA5062 DO 10.1183/13993003.congress-2016.PA5062 VO 48 IS suppl 60 A1 Rogliani, Paola A1 Ora, Josuel A1 Calzetta, Luigino A1 Lucà, Gabriella A1 Matera, Maria Gabriella A1 Cazzola, Mario YR 2016 UL http://erj.ersjournals.com/content/48/suppl_60/PA5062.abstract AB Background The oxidant/antioxidant imbalance is significantly pronounced in patients with COPD exacerbation. N-acetylcysteine (NAC) seems to have an influence in reducing COPD exacerbations via modulating the oxidative stress, but there are discordant findings on the actual anti-oxidant activity of NAC.Aim We aimed to pharmacologically characterize the anti-oxidant effect of NAC in an ex vivo model of COPD exacerbation.Methods The influence of NAC was assessed on the contractile response and anti-oxidant profile in human isolated bronchi incubated overnight with Krebs-Henseleit buffer solution (control) or lipopolysaccharide (LPS, 100 ng/ml).Results LPS desensitized isolated airways against the transmural stimulation (-55%±13%, P<0.05 vs. control). Concentrations of NAC ≥10μM restored the physiological contractile response in LPS stimulated bronchi (Emax 99±19% vs. control, P<0.05 vs. LPS), whereas lower concentrations (<10μM) did not modulate this effect. Concentrations of NAC ≥1μM reduced the pro-oxidant response (peroxidase activity, hydrogen peroxide, malondialdehyde, nitric oxide: overall -31±2%; P<0.05 vs. LPS), and improved the anti-oxidant response (total anti-oxidant capacity, glutathione, superoxide dismutase: overall +97±8%; P<0.05 vs. LPS) induced by LPS. Lower concentrations of NAC (<1μM) did not modulate the bronchial oxidative imbalance (P>0.05 vs. LPS).Conclusions The results of this study demonstrated that concentrations of NAC ≥10μM are required to normalize the dysfunctional contractility of human bronchi and concentrations of NAC ≥1μM improve the oxidative imbalance in an ex vivo model of COPD exacerbation.