Hildebrandt E, Suttie J W
J Pharm Pharmacol. 1984 Sep;36(9):586-91. doi: 10.1111/j.2042-7158.1984.tb04903.x.
Salicylate antagonizes the vitamin K-dependent biosynthesis of clotting factors in the rat and produces an elevation of the ratio of vitamin K epoxide to vitamin K in the liver. Vitamin K epoxide is reduced to vitamin K by a vitamin K epoxide reductase, and 1 mM salicylate was required to cause a 50% inhibition of the dithiothreitol-dependent in-vitro reduction of vitamin K epoxide by this enzyme. This enzyme was, however, inhibited 50% by as little as 70-80 microM salicylate when reducing equivalents for the reaction were furnished by endogenous cytosolic reductants. This effect on the cytosolic reductant supply was shown to be unrelated to a previously demonstrated inhibition of DT-diaphorase by salicylate. The concentrations of salicylate at which significant inhibitory effects are exerted in-vitro (50-100 microM) are below the 200 microM levels observed in the livers of rats given an anticoagulating dose of salicylate.
水杨酸盐可拮抗大鼠体内维生素K依赖的凝血因子生物合成，并使肝脏中维生素K环氧化物与维生素K的比例升高。维生素K环氧化物通过维生素K环氧化物还原酶还原为维生素K，该酶对二硫苏糖醇依赖的维生素K环氧化物体外还原反应产生50%抑制作用时，所需水杨酸盐浓度为1 mM。然而，当反应的还原当量由内源性胞质还原剂提供时，低至70 - 80 microM的水杨酸盐就能对该酶产生50%的抑制作用。水杨酸盐对胞质还原剂供应的这种影响与之前所证明的水杨酸盐对DT - 黄递酶的抑制作用无关。体外产生显著抑制作用的水杨酸盐浓度（50 - 100 microM）低于给予抗凝剂量水杨酸盐的大鼠肝脏中观察到的200 microM水平。
