Abstract
The effects of anti-allergic drugs with or without H 1-receptor antagonism on the NADPH oxidase (EC 1.6.99.6) from human neutrophils in both whole-cell and fully soluble (cell-free) systems were investigated. Three anti-allergic drugs with H 1-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 these drugs required for 50% inhibition of the oxidase (Ic 50) were: azelastine—0.7 μM in the whole-cell system and 0.5 μM in the cell-free system; ketotifen—60 μM in the whole-cell system and 6.8 μM in the cell-free system; and oxatomide—25 μM in the whole-cell system and 9.7 μM in th cell-free system. In addition, in the cell-free system, these drugs did not change the K m values for the NADPH of the oxidase. However, these drugs did not inhibit the Superoxide generation of NADPH oxidase after its activation in whole-cell and cell-free systems, suggesting that these drugs do not have superoxide-scavenger actions. Concentrations of less than 200 μM of anti-allergic drugs without H 1receptor antagonism, tranilast, repirinast and ibudilast, did not inhibit neutrophil NADPH oxidase in whole-cell and cell-free systems. The Ic 50 of hydrocortisone in the cell-free system was 60 μM. These results suggest that anti-allergic drugs with H 1-receptor antagonism inhibit activation of the solubilized membrane-bound enzyme by sodium dodecyl sulfate in cell-free systems and that they have much stronger anti-inflammatory action than hydrocortisone.
Published Version
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