Effects of various drugs on superoxide generation, arachidonic acid release and phospholipase A2 in polymorphonuclear leukocytes.

Effects of Azelastine on Neutrophil Chemotaxis, Phagocytosis and Oxygen Radical Generation.

“…Taniguchi et al (13,14) have previously reported that azelastine inhib its the amount of 02 generated by neutro phils, and this was confirmed by the results of the present investigation. In addition, our re sults show that the drug reduced the amount of H202 and OH generation by neutrophils, respectively.…”

“…In vitro experiments have demonstrated that azelastine is a potent inhibitor of the arachido nic acid release and 02 generation by fMLP stimulated neutrophils, but weak inhibitors of phospholipase A2 (13). Furthermore, 02 gen eration by phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils is also reduced in the presence of the drug (14).…”

“…Regarding its mechanisms of action, the drug has been demonstrated to inhibit not only histamine release but also leukotriene re lease, and it also antagonizes histamine as well as leukotrienes (10)(11)(12). It has been recently reported that azelastine decrease 02 genera tion by neutrophils (13,14). However, the effects on neutrophil chemotaxis, phagocytosis and each kind of ROS, especially OH which is the most toxic oxidant, generated by both neutrophils and the xanthine-xanthine oxidase system, have not yet been examined.…”

Action sites of antiallergic drugs on human neutrophils.

“…In previous studies, we have demonstrated that metabolic bursts of rabbit polymorphonu clear leukocytes such as superoxide genera tion and arachidonic acid releases were effec tively diminished by the newly developed antiallergic drug, azelastine (17,20). In this study, attempts were made to examine five representative new drugs including oxa tomide, azelastine, tranilast, repirinast and amplexanox on superoxide generation, arachi donic acid release and LTB4 formation from the stimulated human neutrophils.…”

“…On the other hand, the acidic agents were developed on the basis of ob servations that DSCG (disodium cromogly cate), bicalein and caffeic acid are inhibitors of chemical mediator release (12,15). We have previously shown that superoxide generation, arachidonic acid release as well as changes of membrane potential were sup pressed by one of the basic antiallergic agents, azelastine (16)(17)(18). In this study, we attemped to compare the inhibitory effects of antial lergic drugs on the release of arachidonic acid, leukotriene B4 and superoxide from ac tivated human neutrophils to clarify the action sites of the various basic and acidic anti allergic drugs.…”