The inhibitory effect of ambroxol on hypochlorous acid-induced tissue damage and respiratory burst of phagocytic cells.
Ambroxol (100 microM and 1 mM) and the thiols (all 1 mM), glutathione, tiopronin and cysteine, significantly attenuated the myeloperoxidase, H(2)O(2) 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 completely decomposed both HOCl and H(2)O(2), while ambroxol up to 1 mM did not show a scavenging action on H(2)O(2). Ambroxol (1 to 100 microM) and 1 mM thiol compounds markedly inhibited the HOCl-induced alteration of elastase activity. Thiol compounds significantly attenuated the HOCl production caused by degraded immunoglobulin G-activated neutrophils. Ambroxol depressed superoxide and H(2)O(2) production induced by degraded immunoglobulin G-activated neutrophils and by lipopolysaccharide-activated alveolar macrophages in a dose-dependent manner. The results show that ambroxol may interfere with oxidative tissue damage and decrease proteolytic tissue destruction by attenuation of oxidative stress-induced inactivation of alpha(1)-antiproteinase through both decomposition of HOCl and inhibition of the respiratory burst in phagocytic cells.
Cho
Y
Y
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea.
Jang
Y Y
YY
Han
E S
ES
Lee
C S
CS
D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004586:Electrophoresis; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism* / Q000633:toxicity; D066298:In Vitro Techniques; D019272:Leukocyte Elastase / Q000494:pharmacology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D018375:Neutrophil Activation; D016877:Oxidants / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D008625:Tiopronin / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000975:Antioxidants; D016877:Oxidants; D000515:alpha 1-Antitrypsin; D013481:Superoxides; D000551:Ambroxol; D006997:Hypochlorous Acid; D003094:Collagen; D008625:Tiopronin; D019272:Leukocyte Elastase; D005978:Glutathione; D003545:Cysteine