In vitro effects of synthetic antioxidants and vitamin E on arachidonic acid metabolism and thromboxane formation in human platelets and on platelet aggregation

Abstract

The “in vitro” effects of α-tocopherol, butylhydroxytoluene (BHT) and butylhydroxyanisole (BHA) were studied on aggregation of human platelets induced by collagen and arachidonic acid (AA), on the metabolic conversion of 14C AA through the cyclooxygenase and lipoxygenase pathways and on the formation of thromboxane B 2 (TXB 2) in washed platelets after stimulation with collagen. Vitamin E completely inhibited AA induced platelet aggregation only at high concentration (mM) and after 10 minutes of preincubation, with limited effects on AA metabolism in platelets and no effect on TXB 2 formation from endogenous substrate. BHA completely inhibited platelet aggregation in the 10 −6M range, gave 50% inhibition of AA metabolism in the 10 −5M range and almost complete inhibition of thromboxane formation in the 10 −4M range. BHT was about 100 times less active on platelet aggregation and AA metabolism. The lipoxygenase and cyclooxygenase pathways were differentially affected at low concentrations of BHA and only at concentrations greater than 5×10 −5M were both pathways depressed.