title: Ambroxol inhibits peroxynitrite-induced damage of alpha1-antiproteinase and free radical production in activated phagocytic cells.
abstract: The present study examined the effect of ambroxol on toxic action of peroxynitrite and the respiratory burst in activated phagocytic cells. Ambroxol decreased the inactivation or destruction of alpha1-antiproteinase induced by peroxynitrite (ONOO-) or hypochlorous acid (HOCl), which was similar to penicillamine and glutathione and was greater than diclofenac sodium and naproxen sodium. Ambroxol significantly decreased ONOO--mediated tyrosine nitration and iron plus EDTA-mediated degradation of 2-deoxy-D-ribose. Ambroxol significantly attenuated the production of superoxide, hydrogen peroxide, HOCl, and nitric oxide in fMLP- or IL-1-activated phagocytic cells, while the inhibitory effects of antiinflammatory and thiol compounds were only observed in HOCl production. Ambroxol and antiinflammatory drugs did not show a cytotoxic effect on macrophages. The results suggest that ambroxol protects tissue components against oxidative damage by an action different from antiinflammatory drugs. Ambroxol may interfere with oxidative damage of alpha1-antiproteinase through a scavenging action on ONOO- and HOCl and inhibition of the respiratory burst of phagocytic cells.
authors.affiliation: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea. leecs@cau.ac.kr
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Jang
authors.forename: Joon Sup
authors.initials: JS
authors.lastname: Song
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Song
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Han
mesh_terms: D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010586:Phagocytes / Q000187:drug effects* / Q000201:enzymology; D016897:Respiratory Burst / Q000187:drug effects; D000515:alpha 1-Antitrypsin / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000515:alpha 1-Antitrypsin; D030421:Peroxynitrous Acid; D000551:Ambroxol; D006997:Hypochlorous Acid