[Biochemical study on anti-inflammatory action of anti-allergic drugs--with regard to NADPH oxidase].
The effects of anti-allergic drugs with or without H1-receptor antagonism on the NADPH oxidase from human neutrophils in both whole-cell and fully soluble (cell-free) systems were investigated. Three anti-allergic drugs with H1-receptor antagonism, azelastine, ketotifen and oxatomide, were found to inhibit the superoxide generation of human neutrophils exposed to phorbol myristate acetate in a whole-cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in a cell-free system. The concentrations of three drugs required for 50% inhibition of the oxidase (IC50) were as follows: azelastin--0.7 microM in the whole-cell system and 0.5 microM in the cell-free system, ketotifen--60 microM in the whole-cell system and 6.8 microM in the cell-free system, and oxatomide--25 microM in the whole-cell system and 9.7 microM in the cell-free system. In addition, in the cell-free system, these drugs did not change the Km values for the NADPH of the oxidase. However, micromoles of tranilast, an anti-allergic drug without H1-receptor antagonism, did not inhibit neutrophil NADPH oxidase in the whole-cell and cell-free systems. The IC50 of hydrocortisone in the cell-free system was 60 microM. These results suggest that anti-allergic drugs with H1-receptor antagonism inhibit reconstitution of the solubilized membrane-bound enzyme by sodium dodecyl sulfate in cell-free systems and that they have a strong anti-inflammatory action. Anti-allergic drugs are not the drugs of first choice for asthma, but these drugs, especially basic anti-allergic drugs, should be used more frequently for the treatment of chronic asthma, infectious-typed asthma and mixed-typed asthma closely associated with acute and chronic inflammation of the airways as well as atopic asthma.
Department of Medicine, Kawasaki Medical School.
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Umeki
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007665:Ketotifen / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010793:Phthalazines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006634:Histamine H1 Antagonists; D010793:Phthalazines; D010879:Piperazines; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C015408:oxatomide; D007665:Ketotifen; C020976:azelastine