The inhibitory effect of ambroxol on hypochlorous acid-induced tissue damage and respiratory burst of phagocytic cells

Ambroxol (100 mu M and 1 mM) and the thiols tall 1 mM), glutathione, tiopro nin and cysteine, significantly attenuated the myeloperoxidase, H2O2 and Cl - system-caused destruction of alpha(1)-antiproteinase and the HOCl-induced destruction of collagen, whereas they did not affect the elastase-induced destruction of collagen. Glutathione, tiopronin and cysteine almost complet ely decomposed both HOCl and H2O2, while ambroxol up to 1 mM did not show a scavenging action on H2O2. Ambroxol (1 to 100 mu M) and 1 mM thiol compoun ds markedly inhibited the HOC1-induced alteration of elastase activity. Thi ol compounds significantly attenuated the HOCl production caused by degrade d immunoglobulin G-activated neutrophils. Ambroxol depressed superoxide and H2O2 production induced by degraded immunoglobulin G-activated neutrophils and by lipopolysaccharide-activated alveolar macrophages in a dose-depende nt manner. The results show that ambroxol may interfere with oxidative tiss ue damage and decrease proteolytic tissue destruction by attenuation of oxi dative stress-induced inactivation of alpha(2)-antiproteinase through both decomposition of HOCl and inhibition of the respiratory burst in phagocytic cells. (C) 1999 Elsevier Science B.V. All rights reserved.