title: Inhibitory effect of ambroxol on superoxide anion production and generation by murine lung alveolar macrophages.
abstract: We examined the effect of ambroxol on superoxide anion production before and generation after phorbol-myristate acetate (PMA) stimulation of lung alveolar macrophages. Lung free cells including lung alveolar macrophages were obtained from Fischer 344 rats and guinea pigs using bronchoalveolar lavage. The superoxide anion produced by lung alveolar macrophages with or without stimulation of PMA was measured by lucigenin-dependent chemiluminescence method using a photon counter. Ambroxol inhibited the superoxide anion production and generation by lung alveolar macrophages harvested from both F344 rats and guinea pigs in a dose-dependent fashion. Approximately 16 mumol/L of ambroxol inhibited 50% of superoxide production of lung alveolar macrophages in rats and guinea pigs, whereas a slightly greater dose of ambroxol, i.e., 18-26 mumol/L, was necessary to inhibit 50% of PMA-enhanced superoxide generation by lung alveolar macrophages. These results suggest that ambroxol acts as an antioxidant in murine lungs and may be a potential therapeutic option for reactive oxygen species-associated lung disorders including bronchial asthma.
authors.affiliation: Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Teramoto
authors.forename: T
authors.initials: T
authors.lastname: Matsuse
authors.forename: E
authors.initials: E
authors.lastname: Ohga
authors.forename: H
authors.initials: H
authors.lastname: Katayama
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Ouchi
mesh_terms: D000166:Acridines; D000551:Ambroxol / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000032:analysis / Q000037:antagonists & inhibitors*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002374:Catalase / Q000494:pharmacology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008163:Luminescent Measurements; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D011916:Rats, Inbred F344; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D000166:Acridines; D000838:Anions; D013481:Superoxides; D000551:Ambroxol; C033472:10,10'-dimethyl-9,9'-biacridinium; D002374:Catalase; D013482:Superoxide Dismutase