5-hydroxy-6-8-11-14-eicosatetraenoic-acid and phenidone

Our aim was to assess the potential role of lipoxygenase (LO) products in neointimal formation following vascular injury. We investigated the effect of LO pathway inhibition, by phenidone, on the concentration of 12- and 5-hydroxyeicosatetraenoic acid (12- and 5-HETE) in rat whole blood and in aortic tissue. We also examined the effect of phenidone on myoneointimal formation in balloon-injured rat carotid arteries. Phenidone significantly decreases the concentration of HETEs in aortic tissue, and decreases neointimal size even though there is no difference in the BrdU index. These data indicate that the LO product participates in developing neointima following balloon-induced vascular injury, and that the LO blocker phenidone decreases neointimal size possibly by suppressing migration of smooth muscle cells.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Angioplasty, Balloon; Animals; Aorta, Thoracic; Carotid Artery Injuries; Cell Division; Hydroxyeicosatetraenoic Acids; Lipoxygenase; Lipoxygenase Inhibitors; Male; Pyrazoles; Rats; Rats, Sprague-Dawley; Tunica Intima

The role of specific products of the lipoxygenase pathway of arachidonic acid metabolism has been investigated in the Friend erythroleukemia cell line, a model system for erythroid cell differentiation. When triggered with agents such as hexamethylene-bis-acetamide, these cells mature as normal erythroid cells. 15-Hydroxyeicosatetraenoic acid (15-HETE) was identified by reverse-phase high-performance liquid chromatography and by radioimmunoassay as the principal lipoxygenase metabolite produced by Friend cells. Its production was significantly lower (903 +/- 73 pg/ml) in stationary-phase cells compared with logarithmic-phase cells (1,496 +/- 24 pg/ml). In addition, inhibitors of both the cyclooxygenase and lipoxygenase pathways (phenidone, BW 755C, caffeic acid, nordihydroguaiaretic acid and BW 4AC) significantly blocked DNA synthesis (P less than 0.05), whereas neither specific inhibitor of the cyclooxygenase pathway (aspirin or sodium meclofenate) blocked DNA synthesis. The addition of 15-hydroperoxyeicosatetraenoic acid as well as 15-HETE to Friend cells produced an increase in DNA synthesis as assessed by [3H]thymidine incorporation in differentiating cells but not in proliferating cells. These data support a role for 15-lipoxygenase products of arachidonic acid metabolism in maintaining DNA synthesis.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Arachidonate 15-Lipoxygenase; Arachidonic Acids; Cell Differentiation; Cell Division; Cell Line; Cell Survival; Clone Cells; DNA Replication; Hydroxyeicosatetraenoic Acids; Kinetics; Leukemia, Experimental; Lipoxygenase Inhibitors; Mice; Pyrazoles; Thymidine