Anticoagulant effect of sodium dehydroacetate (DHA‐S) in rats

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Abstract
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. Copyright © 2007 John Wiley & Sons, Ltd.

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