Tazanolast inhibits ozone-induced airway hyperresponsiveness in guinea pigs.
We studied the inhibitory effect of tazanolast, a selective mast-cell-stabilizing drug, on ozone-induced airway hyperresponsiveness in guinea pigs. Airway responsiveness to methacholine peaked at 2 h after ozone exposure (2.0 ppm for 2 h) and the number of neutrophils in bronchoalveolar lavage (BAL) fluid continued to increase until 6 h. Tazanolast administered before ozone exposure at doses of 30, 100, or 300 mg/kg inhibited ozone-induced airway hyperresponsiveness in a dose-dependent manner. However, tazanolast administered after ozone exposure did not inhibit the airway hyperresponsiveness. Tazanolast did not significantly change the cell distribution of BAL cells at 2 h after the exposure. We conclude that tazanolast significantly inhibits ozone-induced airway hyperresponsiveness in guinea pigs. This result suggests that mast cells may play an important role in its development.
Igarashi
A
A
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Iijima
H
H
Tamura
G
G
Shirato
K
K
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D016210:Methacholine Chloride / Q000494:pharmacology; D009504:Neutrophils / Q000473:pathology; D010126:Ozone; D013777:Tetrazoles / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D013777:Tetrazoles; D016210:Methacholine Chloride; D010126:Ozone; C106301:tazanolast