Effects of antiasthma drugs on superoxide anion generation from human polymorphonuclear leukocytes or hypoxanthine-xanthine oxidase system.
Airway inflammation with human polymorphonuclear leukocytes (PMNs) may play an important role in the pathophysiology of bronchial asthma. Superoxide anion (O2-) and other active oxygen species derived from PMNs cause tissue damage. To evaluate the effects of antiasthma drugs on airway inflammation or antioxidative actions due to the inhibition of O2- generation, we investigated the effects of antiallergic drugs, beta-adrenergic agonists, theophylline and corticosteroids, on the in vitro generation of O2- by human PMNs, using a chemiluminescence (CL) method dependent on a Cypridina luciferin analog (MCLA), a highly sensitive and specific CL probe for O2-. We found that azelastine, one of the antiallergic drugs, and isoproterenol inhibited FMLP-induced O2- generation in a dose-dependent fashion, whereas the other drugs exhibited no such inhibitory action except at very high concentrations. Furthermore, we found that isoproterenol inhibited O2- generation from the hypoxanthine-xanthine oxidase system (an O2(-)-generating system) in a dose-dependent fashion, unlike azelastine and the other drugs. These results suggest that azelastine and isoproterenol inhibit the process of O2- generation from PMNs, while isoproterenol also scavenges O2-. These drugs may be beneficial in the treatment of airway inflammation due to O2- generation in bronchial asthma.
Kato
M
M
Department of Pediatrics, Gunma University School of Medicine, Japan.
Morikawa
A
A
Kimura
H
H
Shimizu
T
T
Nakano
M
M
Kuroume
T
T
D000293:Adolescent; D001249:Asthma / Q000097:blood*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002648:Child; D005260:Female; D016166:Free Radical Scavengers; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010793:Phthalazines / Q000494:pharmacology*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D001993:Bronchodilator Agents; D016166:Free Radical Scavengers; D010793:Phthalazines; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014969:Xanthine Oxidase; D007545:Isoproterenol; C020976:azelastine