menaquinone-6 and dehydroacetic-acid

Sodium dehydroacetate (DHA-S) is used as a food additive, preservative and antimicrobial agent. Repeated oral administration of DHA-S in rats induced severe hemorrhage in multiple organs and prolongation of blood coagulation factors. To determine the mechanism of hemorrhage, the protective effect of vitamin K (VK) was investigated. Increased VK-dependent blood coagulation parameters, a prolonged prothrombin time (PT) and an activated partial thromboplastin time (APTT) were observed in rats when DHA-S alone was administered, while only a slight change was observed in animals that received a single injection of vitamin K2 following the DHA-S dosing. These results suggest that DHA-S-induced hemorrhage is caused by a deficiency of vitamin K. In addition, the inhibitory effect of DHA-S on vitamin K1 epoxide reductase (VKOR) activity was measured with an in vitro system using liver microsomes of normal male rats. DHA-S concentration-dependently inhibited VKOR activity similar to warfarin, but the inhibitory concentration was high. Therefore, it was concluded that the DHA-S-induced hemorrhage was caused by a depletion of blood VK, associated with any factors including VKOR inhibition.

Topics: Animals; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Dose-Response Relationship, Drug; Enzyme Inhibitors; Food Additives; Hemorrhage; Liver; Male; Microsomes, Liver; Mixed Function Oxygenases; Partial Thromboplastin Time; Prothrombin Time; Pyrones; Rats; Rats, Sprague-Dawley; Time Factors; Vitamin K 2; Vitamin K Epoxide Reductases