ARACHIDONIC-ACID PEROXIDATION, PROSTAGLANDIN SYNTHESIS AND PLATELET-FUNCTION

Abstract— The initial oxygenation or peroxidation of arachidonic acid seems to be an essential step for the synthesis of cyclic endoperoxides and prostaglandins. There has been some evidence and considerable interest in the role of superoxide anion, hydroxyl radicals or singlet oxygen as a source of oxygen in the formation of the active species (free radicals). A test capable of detecting active intermediates of lipid peroxidation and useful for studying the role of free radicals has been developed. The test resulted from the discovery that vitamin E markedly enhanced the reduction of nitroblue tetrazolium (NBT) during arachidonic acid peroxidation. Intact platelets, microsomes, sheep vesicular gland enzymes or peroxidases could provide essential enzyme activity. NBT and vitamin E when added to platelet microsomes inhibited the conversion of 14C arachidonic acid to HETE, HHT and thromboxanes. The combination also inhibited aggregation of platelets stimulated by collagen, thrombin, ADP and epinephrine. Prolonged incubation with these agents at the highest concentrations used in the study caused no change in morphology and had no deleterious effect on platelet levels of adenine nucleotides and serotonin. Results of our preliminary studies suggest that NBT and vitamin E can detect intermediates of lipid peroxidation, inhibit the conversion of arachidonic acid, prevent platelet aggregation and the release reaction without damaging the platelets morphologically or biochemically. As both the agents are scavengers of free radicals and in combination exert synergistic effects, the test system may serve as a probe in various free radical mediated events and may offer some degree of protection against free radical mediated pathological processes. Copyright © 1978, Wiley Blackwell. All rights reserved