Inhibitory effect of oxatomide on oxygen-radical generation and peptide-leukotriene release from guinea pig eosinophils.
Eosinophils are prominent inflammatory cells which play a critical role in the pathogenesis of allergic diseases and bronchial asthma. The aim of this experiment was to examine the effects of oxatomide (CAS 60607-34-3, KW-4354), an antiallergic agent, on oxygen-radical generation and peptide-leukotriene (p-LT) release from guinea pig eosinophils. Ketotifen (CAS 345080-13-7) and epinastine (CAS 80012-43-7) were used as reference drugs. Eosinophils were isolated from the peritoneal exudate of guinea pigs, in which peritoneal eosinophilia had been induced by injection of horse serum. Oxygen-radicals were measured with luminol-dependent chemiluminescence and p-LT release was measured with enzyme immunoassay. When eosinophils were stimulated with phorbol miristate acetate, oxatomide and ketotifen inhibited the oxygen-radical generation with a concentration required for 50% inhibition (IC50) of 11.7 mumol/l and 28.4 mumol/l. Oxatomide, ketotifen or epinastine showed an inhibition of oxygen-radical generation induced by calcium ionophore A-23187 and the IC50 value was 11.3 mumol/l for oxatomide, 15.1 mumol/l for ketotifen and 27.3 mumol/l for epinastine, suggesting that oxatomide is a more potent inhibitor of oxygen-radical generation than ketotifen and epinastine. Oxatomide also inhibited p-LT release induced by calcium ionophore A-23187 (IC50, 9.83 mumol/l). Ketotifen and epinastine only weakly inhibited p-LT release. These results suggest that oxatomide may regulate inflammatory diseases, such as bronchial asthma, through suppression of eosinophil function.
Ohmori
K
K
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Manabe
H
H
Akuta-Ohnuma
K
K
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*
D018926:Anti-Allergic Agents; D003984:Dibenzazepines; D005609:Free Radicals; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D015289:Leukotrienes; D010879:Piperazines; D000001:Calcimycin; C015408:oxatomide; C053090:epinastine; D007665:Ketotifen