Abstract
Activated neutrophils can release superoxide anion (O-2) and nitric oxide(NO), which subsequently combine with each other to yield peroxynitrite anions(PRXNT), powerful and harmful oxidants that play a direct role in the inflammatory process in COPD and asthma. Budesonide and erdosteine are both active in reducing the release of O-2, NO and PRXNT and can be administered in patients with respiratory diseases. After metabolisation erdosteine produces an active metabolite (Met I) with an SH group. We investigated whether the combination of budesonide(BUD)(Sigma) and Met I(Edmond Pharma) has a synergistic effect in reducing the production and release of O-2, NO and PRXNT using the luminol amplified chemiluminescence(LACL) of in vitro neutrophil bursts with fMLP(5x10-7mol/L) or PMA(2.5x10-6mol/L).In the presence of L-arginine(100μg/ml) a NO donor that increases PRNXT production, BUD(5x10-7, 1x10-6mol/L) reduced LACL by 27.3-37.8%, whereas Met I(5 ,10 μg/ml) reduced LACL by 22.1-32.7% after stimulation with fMLP.When the two drugs were incubated together LACL was significantly inhibited by 35.2-54.5%. Similar results were obtained with PMA. Our findings indicate the presence of a synergistic antioxidant effect when BUD and Met I are given together, wich is of interest in the strategy of counteracting the airway phlogosis present in many respiratory diseases.