Sodium cromoglycate and doxantrazole are oxygen radical scavengers.
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.
Sadeghi-Hashjin
G
G
Dept of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands. g.sadeghi@mail.urmia.ac.ir
Nijkamp
F P
FP
Henricks
P A J
PA
Folkerts
G
G
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
D017382:Reactive Oxygen Species; D013892:Thioxanthenes; D044004:Xanthones; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; D004205:Cromolyn Sodium; C010134:doxantrazole