Effects of antioxidants on cyclooxygenase and lipoxygenase activities in intact human platelets: comparison with indomethacin and ETYA.
Five antioxidative agents (BW755C, 1-naphtol, NDGA, propylgallate and quercetin) were compared with indomethacin and ETYA for their effects on (14C) arachidonic acid metabolism by cyclooxygenase (CO) and lipoxygenase (LPO) enzymes in intact human platelets. All tested compounds inhibited CO activity in a concentration-dependent manner. LPO activity was suppressed by NDGA, propylgallate, quercetin and ETYA but strongly enhanced by BW755C, 1-naphtol and indomethacin. Whereas NDGA and ETYA showed almost equi-potent inhibitory effects towards both fatty acid oxygenases, propylgallate and quercetin were found to be respectively 6.5 and 4 times better inhibitors of LPO than of CO activities. These data indicate that antioxidants affect arachidonic acid metabolism in intact human platelets in different ways: BW755C and 1-naphtol exerted the same activity as indomethacin, a selective CO blocker, whereas NDGA, propylgallate and quercetin behaved as ETYA, a dual CO-LPO inhibitor. Considering their inhibition selectivity, propylgallate and quercetin may serve as prototypes for more specific blockers of LPO activity.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology*; D002396:Catechols / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008084:Lipoxygenase / Q000097:blood*; D009637:Masoprocol; D009284:Naphthols / Q000494:pharmacology; D011435:Propyl Gallate / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D011720:Pyrazoles / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology
D000975:Antioxidants; D002396:Catechols; D005231:Fatty Acids, Unsaturated; D009284:Naphthols; D011720:Pyrazoles; D015117:5,8,11,14-Eicosatetraynoic Acid; C029350:1-naphthol; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol; D011435:Propyl Gallate; D011794:Quercetin; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin