INFLUENCE OF ANTIOXIDANTS ON ARACHIDONIC-ACID METABOLISM AND PLATELET-FUNCTION

Studies from our laboratory demonstrated that the free radical scaveng er, nitro blue tetrazolium, and iron chelators, such as dypyrydil, are potent inhibitors of arachidonic acid oxidation and platelet function . In the present study, we have evaluated the effects of known antioxi dants, such as butylated hydroxyanisol (BHA), butylated hydroxytoluene (BHT), and diphenylamine, on arachidonic acid metabolism and platelet function. Diphenylamine, a common dye intermediate used in hair color formulations, was the most potent inhibitor of arachidonic acid metab olism by platelet cyclooxygenases. Diphenyl and BHA were also potent i nhibitors of arachidonic acid oxidation. Other diphenyl analogues and BHT were relatively poor inhibitors of arachidonic-mediated platelet a ctivation. Results of this study, as well as those of our earlier stud ies, suggest that antioxidants and iron chelators prevent arachidonic acid metabolism and alter platelet function by interfering with the he me/arachidonic acid interaction and blocking cyclooxygenase metabolite s essential for the formation of thromboxane A(2), a potent platelet a gonist. (C) 1994 Academic Press, Inc.