Comparison of the relative activities of alpha-tocopherol and PMC on platelet aggregation and antioxidative activity

In this study, PMC (2,2,5,7,8,-pentamethyl-6-hydroxychromane), a potent ant ioxidant derived from alpha-tocopherol, dose-dependently inhibited agonist- induced platelet aggregation in human platelet-rich plasma. PMC is over 5-1 0 times more potent than alpha-tacopherol in inhibiting human platelet aggr egation. Moreover, PMC (25-350 mu M) dose-dependently reduced the relative fluorescence intensity of platelet membrane tagged with diphenylhexatriene (DPH). PMC is about 6-times more potent than a-tocopherol on this effect. F urthermore, antioxidative activity of PMC was investigated using two in vit ro models. PMC inhibited non-enzymatic iron-induced lipid peroxidation in r at brain homogenates with an IC50 value of 0.21+/-0.05 mu M. It was more po tent than alpha-tocopherol or other classical antioxidants. PMC also scaven ged the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). The conce ntration of PMC resulting in a decrease of 0.20 in the absorbance of DPPH w as about 12.1+/-3.6 mu M, was comparable in potency to alpha-tocopherol, bu tylated hydroxytoluence and Trolox. The antiplatelet activity of PMC may po ssibly be due initially to an increase in fluidity of the platelet membrane followed by inhibition of platelet aggregation. Our results indicate that PMC is a potentially effective antioxidant and antiaggregating agent, and c ould be helpful the design of compounds with more clinical effectiveness.