title: Sodium cromoglycate and doxantrazole are oxygen radical scavengers.
abstract: The effects of two mast cell stabilisers, sodium cromoglycate (SCG) and doxantrazole, on the formation of reactive oxygen species (ROS) were studied. Guinea-pig alveolar macrophages (AMs) generated lucigenin-dependent chemiluminescence (LDCL). This was increased when the cells were stimulated by phorbol myristate acetate (PMA) or zymosan (by 133% and 464%, respectively, in total LDCL over 60 min). SCG decreased PMA-induced LDCL at higher concentrations (10 mM, by 55%) than doxantrazole (1 mM, by 75%). SCG decreased radical production by AMs in response to zymosan in a concentration-dependent manner by < or = 72%. Doxantrazole (0.1-1 mM) diminished total LDCL by 30-80%. In addition, glucose oxidase led to LDCL generation when incubated with glucose in a cell-free medium. This was inhibited by 47-83% in the presence of SCG or doxantrazole. SCG and doxantrazole inhibited the hydrogen peroxide- and peroxynitrite-induced LDCL by < or = 92%. Moreover, these drugs slightly increased the survival rate of the AMs. It is concluded that doxantrazole- and sodium cromoglycate-inhibited lucigenin-dependent chemiluminescence production by guinea-pig alveolar macrophages is due to a direct scavenging effect on reactive oxygen species. Doxantrazole is approximately 10-times more potent. Mast cell stabilisers may be effective in allergic asthma not only by preventing the allergen-induced mediator release, but also by preventing radical-induced lung damage.
authors.affiliation: Dept of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands. g.sadeghi@mail.urmia.ac.ir
authors.forename: G
authors.initials: G
authors.lastname: Sadeghi-Hashjin
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: P A J
authors.initials: PA
authors.lastname: Henricks
authors.forename: G
authors.initials: G
authors.lastname: Folkerts
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D004205:Cromolyn Sodium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D008163:Luminescent Measurements; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D011336:Probability; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013892:Thioxanthenes / Q000494:pharmacology*; D044004:Xanthones; D015054:Zymosan / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D013892:Thioxanthenes; D044004:Xanthones; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; D004205:Cromolyn Sodium; C010134:doxantrazole