Effects of selenium, vitamin E and vitamin C on human prostacyclin and thromboxane synthesis in vitro.
The effects of three antioxidants, selenium, vitamin E and vitamin C, on the production of anti-aggregatory prostacyclin (PGI2) by human endothelial cells and lung tissue as well as on the production of pro-aggregatory thromboxane A2 (TxA2) by human platelets and lung tissue in vitro were studied. Selenium had no effect on endothelial PGI2 synthesis but it dose-dependently inhibited the platelet production of TxA2 (84% at 10(-3) mol/l) and productions of PGI2 (64%) and TxA2 (72%) by human lung. Selenium inhibited platelet TxA2 synthesis much less in the presence of exogenous arachidonic acid (AA) (14% instead of 84%), suggesting that selenium exerts its effect predominantly on phospholipase A2. Vitamin E had no effect on endothelial PGI2, pulmonary PGI2 or TxA2 syntheses but it strongly inhibited platelet TxA2 production (50% at 10(-3) mol/l). This inhibition was only partly (from 50% to 30%) counteracted by exogenous AA suggesting that vitamin E affects both phospholipase A2 and a further step(s) in the TxA2 synthetizing cascade. Vitamin C stimulated endothelial cell PGI2 production (80% at 10(-2) mol/l) but it could not counteract the inhibition of PGI2 production (83%) exerted by 10(-2) mol/l tert-butyl hydroperoxide (TBHP), a promoter of lipid peroxidation. Vitamin C had no effect on pulmonary PGI2 production but it inhibited pulmonary TxA2 formation (38% at 10(-3) mol/l). Slight inhibition of platelet TxA2 production from endogenous AA (6%) turned to slight stimulation (8%) with exogenous AA. The in vivo significance of these results is not yet known.
D000975:Antioxidants / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010545:Peroxides / Q000494:pharmacology; D012643:Selenium / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D014810:Vitamin E / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D000975:Antioxidants; D001095:Arachidonic Acids; D010545:Peroxides; D014810:Vitamin E; D013928:Thromboxane A2; D020122:tert-Butylhydroperoxide; D011464:Epoprostenol; D012643:Selenium; D001205:Ascorbic Acid; D007213:Indomethacin