Therapeutic options for 5-lipoxygenase inhibitors.

Abstract:

:5-Lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) into leukotriene (LT) A(4) and 5-hydroperoxyeicosatetraenoic acid. LTA(4) can then be converted into LTB(4) by LTA(4) hydrolase or into LTC(4) by LTC(4) synthase and the LTC(4) synthase isoenzymes MGST2 and MGST3. LTB(4) is a potent chemoattractant for neutrophils, eosinophils and monocytes leading to adherence of phagocytes to vessel walls, neutrophil degranulation and release of superoxide anions. LTC(4) and its metabolite, LTD(4), 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 CysLT(1) 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.

journal_name

Pharmacol Ther

authors

Werz O,Steinhilber D

doi

10.1016/j.pharmthera.2006.05.009

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

701-18

issue

3

eissn

0163-7258

issn

1879-016X

pii

S0163-7258(06)00107-0

journal_volume

112

pub_type

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