Metabolism of arachidonic acid by lipoxygenase in inflammatory cells and lung tissue results in the production of a number of hydroperoxy- and hydroxyeicosatetraenoic acids (HPETEs and HETEs respectively) and leukotrienes. Leukotrienes C4(LTC4) and D4(LTD4) are bronchoconstrictors and increase vascular permeability. Lipoxygenase inhibitors block leukotriene synthesis, and thereby reduce prolonged allergic bronchoconstriction and indomethacin-induced airways hyperreactivity. HPETEs and HETE attract neutrophils and eosinophils to inflammatory sites. Lipoxygenase inhibitors reduce HPETE and HETE synthesis and suppress chemotaxis and chemokinesis of neutrophils and eosinophils induced by inflammatory stimuli. Lipoxygenase inhibitors are therefore potential anti-asthmatic and anti-inflammatory agents.
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