Indirect inhibition of vitamin K epoxide reduction by salicylate

Article abstract of 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 μM 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 μM) are below the 200 μM levels observed in the liver of rats given an anticoagulating dose of salicylate.