Studies from our laboratory demonstrated that the free radical scavenger, 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 antioxidants, 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 metabolism by platelet cyclooxygenases. Diphenyl and BHA were also potent inhibitors of arachidonic acid oxidation. Other diphenyl analogues and BHT were relatively poor inhibitors of arachidonic-mediated platelet activation. Results of this study, as well as those of our earlier studies, suggest that antioxidants and iron chelators prevent arachidonic acid metabolism and alter platelet function by interfering with the heme/arachidonic acid interaction and blocking cyclooxygenase metabolites essential for the formation of thromboxane A2, a potent platelet agonist.
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