Vitamin K deficiency in male rats fed diets containing butylated hydroxytoluene (BHT).

Abstract Butylated hydroxytoluene (BHT), a commonly used food antioxidant, induces prolonged prothrombin time and then a hemorrhagic death in male rats. The mechanism of this hemorrhage produced by BHT was studied, compared with that induced by dicoumarol which is a well-known vitamin K antagonist. The reduction of activities of vitamin K-dependent clotting factors II, VII, IX, and X was observed in BHT or dicoumarol-treated rats. Administration of vitamin K 1 and K 2 corrected the prolongation of prothrombin time. On the other hand, the administration of vitamin K 3 did not correct the prolongation by dicoumarol as already reported by others, whereas that of vitamin K 3 corrected the prolongation produced by BHT. Liver DT-diaphorase activity, which may participate in the metabolism of vitamin K and is inhibited by dicoumarol in vitro , increased in BHT-treated rats four to five times compared to that of untreated control rats. Dicoumarol-treated rats showed no change in the DT-diaphorase activity. These results suggest that the mechanism of BHT-induced hemorrhage differs from that of dicoumarol-induced hemorrhage.