Abstract
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.
- Copyright ©the authors 2016
