Comparative effects of inhibitors of arachidonic acid metabolism on erythropoiesis.
The effects of a variety of inhibitors of the arachidonic acid metabolic pathway have been tested on the growth of early erythroid progenitor cell-derived colonies (CFU-E and BFU-E) in an attempt to discern whether products of the cyclo-oxygenase pathway or lipoxygenase pathway are essential for erythropoiesis. Murine erythroid progenitor cells obtained from fetal livers were cultured in the presence of erythropoietin for CFU-E and of interleukin 3 for BFU-E colony formation in response to the cyclo-oxygenase inhibitors, aspirin or sodium meclofenamate, and the lipoxygenase inhibitors, BW755C, nordihydroguiaretic acid (NDGA), phenidone, and butylated hydroxyanisole (BHA). The most potent inhibitor of colony formation (both CFU-E and BFU-E) was the selective lipoxygenase inhibitor, BW755C, followed by NDGA, phenidone and BHA. Neither aspirin nor sodium meclofenamate (10(-4) - 10(-6)M) significantly (p less than 0.05) inhibited CFU-E or BFU-E formation. These results support the hypothesis that lipoxygenase products of arachidonic acid metabolism may be essential for erythroid cell proliferation/differentiation.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors; D004920:Erythropoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D002083:Butylated Hydroxyanisole; D016718:Arachidonic Acid; D008469:Meclofenamic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; C015429:phenidone; D001241:Aspirin