IN VITRO AND IN VIVO EFFECT OF VITAMIN E ON NORMAL HUMAN PLATELETS. AGGREGATION AND ARACHIDONIC ACID (AA) METABOLISM

Abstract

Oxygenated metabolism of AA through cyclooxygenase and lipoxygenase pathways involves peroxide species and vitamin E has been extensively studied as an agent that could reduce this lipid peroxidation. In the present study, effects of vitamin E has been investigated upon AA metabolism in normal human platelets with both in vivo and in vitro approaches. Using low doses of vitamin E either in vivo or in vitro, we have succeeded to almost double plasma and platelet a-tocopherol (determinated by HPLC). Despite such an enrichment platelet aggregation induced by agents involved in the AA cascade (collagen, arachidonate and U46619) was not affected. Similarly, the oxygenation of exogenous AA determined by HHT, HETE and TxB2 production was not modified. When the oxygenated products were measured after thrombin stimulation, some variations could be noted, although rarely significant. The tendency was a decrease after in vitro enrichment and an increase when enrichment occured in vivo. Basal oxygenated metabolism of AA in vivo was assessed by measuring 6-Keto-PGFla, 2,3-dinor-6-Keto-PGFla, TxB2 and 2,3-dinor-TxB2 in urine. All of them tended to increase after vitamin E intake, although not significantly. The oxygenation of eicosapentaenoic acid, which is markedly potentiated by AA through its hydroperoxide, 12 HPETE, was not altered after vitamin E treatment, confirming that vitamin E does not alter the specific peroxidation of polyunsaturated fatty acids in normal platelets. We conclude that vitamin E supplement does not affect the AA dependent aggregation neither the oxygenated metabolism of AA in normal human platelets. This does not exclude that it might be however useful in platelets that exhibit a relative deficiency in this vitamin (e.g. diabetes and aging) where it could slow down both AA peroxidation and aggregation.