Abstract
In vitroandin vivoeffect of eicosapentaenoic acid (EPA), a potent anti-platelet aggregatory substance, on arachidonic acid metabolism in rat peritoneal macrophages was studied.In vitrostudy demonstrated that EPA decreased dose-dependently the release of14Carachidonic acid (AA) from14C-AA prelabeled macrophages and the conversion of the released14C-AA to its cyclooxygenase and lipoxygenase metabolites. This may indicate the impairment of release mechanism of AA from macrophage membrane phospholipids. In addition an increased ratio of lipoxygenase products to cyclooxygenase products by addition of EPA suggests that possible inhibition of cyclooxygenase by EPA seems most likely to shunt released AA into lipoxygenase pathway. When 60mg/kg of EPA-ethylester (75% purity) was orally given to rats for 4 weeks, a significant rise in EPA content in macrophage phospholipids was noted while AA content was unchanged. An apparent decrease in the released AA and its both lipoxygenase and cyclooxygenase metabolites indicates that incorporated EPA in macrophage membrane phospholipids may suppress the release of AA from macrophage membrane phospholipids. These evidences described above raise a possibility that EPA may suppress macrophage functions such as migration or lysosomal enzyme secretion. Accordingly EPA may act not only as anti-thrombogenic or anti-atherogenic but also as anti-inflammatory agent.
