Lower levels of lipid peroxidation in human platelets incubated with eicosapentaenoic acid.
The modulatory effects of eicosapentaenoic acid (EPA) on platelet arachidonic acid (AA) metabolism were applied to an in vitro model of oxidant stress. Unstimulated normal human blood platelets were first treated with a thiol-oxidizing agent, azodicarboxylic acid bis(dimethylamide) (diamide) (1 microM), and then incubated with a low concentration of EPA (100 nM). Diamide treatment led to a lower alpha-tocopherol content compared to control. Formation of MDA, a marker of the overall lipid peroxidation, as well as formation of 12-hydroxyeicosatetraenoic acid (12-HETE), the 12-lipoxygenase end-product of AA, were both higher in diamide-treated platelets. Subsequent incubation of diamide-treated platelets with EPA counteracted the effects of oxidant stress induced pharmacologically by diamide. Interestingly, EPA prevented the alpha-tocopherol level from falling and the overall lipid peroxidation from increasing as it did during diamide treatment. In particular, incubation of diamide-treated platelets with EPA led to significantly lower amounts of 12-HETE. Conversely, preincubation of platelets with 100 nM EPA protected cells from oxidizing effects induced by diamide treatment, either on the level of lipid peroxides or on the antioxidant status. These results indicate that, in this particular model, EPA permitted platelets to have control levels of tocopherol, MDA and 12-HETE despite diamide treatment. Low concentrations of EPA might have prevented the increase of lipid hydroperoxides and especially the transient accumulation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE).
Calzada
C
C
Institut National de la Santé et de la Recherche Médicale U352, Chimie Biologique INSA, Villeurbanne, France.
Véricel
E
E
Lagarde
M
M
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis; D015227:Lipid Peroxidation; D008055:Lipids / Q000032:analysis; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008315:Malondialdehyde / Q000032:analysis; D014810:Vitamin E / Q000032:analysis
D006893:Hydroxyeicosatetraenoic Acids; D008055:Lipids; D016859:Lipoxygenase Inhibitors; D014810:Vitamin E; D016718:Arachidonic Acid; D008315:Malondialdehyde; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015118:Eicosapentaenoic Acid