Therapeutic options for 5-lipoxygenase inhibitors

Abstract

5-Lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) into leukotriene (LT) A4 and 5-hydroperoxyeicosatetraenoic acid. LTA4 can then be converted into LTB4 by LTA4 hydrolase or into LTC4 by LTC4 synthase and the LTC4 synthase isoenzymes MGST2 and MGST3. LTB4 is a potent chemoattractant for neutrophils, eosinophils and monocytes leading to adherence of phagocytes to vessel walls, neutrophil degranulation and release of superoxide anions. LTC4 and its metabolite, LTD4, are potent bronchoconstrictors that increase vascular permeability and stimulate mucus secretion from airways. Recent data also suggest that LT have an immunomodulatory role. Due to these properties, the increased biosynthesis of LT in asthma, and based upon clinical data obtained with CysLT1 receptor antagonists in asthma patients, there is a consensus that CysLT play a prominent role in asthma. In this review, we summarize the knowledge on possible functions of the 5-LO pathway in various diseases like asthma, cancer and cardiovascular events and review the corresponding potential therapeutic roles of 5-LO inhibitors. © 2006 Elsevier Inc. All rights reserved.