Preventive Effects of Phylloquinone on Hemorrhagic Death Induced by Butylated Hydroxytoluene in Male Rats

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Abstract
The effects of vitamin K on hemorrhagic death induced by dietary butylated hydroxytoluene (BHT) were studied. Male Sprague-Dawley rats were given BHT or two phenolic antioxidants (2,4,6-tri-tert-butylphenol and 2,5-di-tert-butylhydroquinone) in combination with a 24% casein basal diet. The levels of the phenols were chosen to nearly equal LD50 (40 days). Hemorrhagic death, hemorrhage and a decrease in prothrombin index caused by 1.20% BHT were prevented by simultaneously adding phylloquinone (0.68 µmole/kg/day). Phylloquinone also inhibited the effect of the related phenolic antioxidants. Ten nanomoles of phylloquinone injected into the femoral vein on day 3 of feeding 1.2% BHT increased the prothrombin concentration from 28% of normal to 100% of normal within 18 to 24 hours. Phylloquinone oxide also prevented hypoprothrombinemia due to BHT. These results suggest that BHT-induced hemorrhagic death may be caused by direct and/or indirect vitamin K deficiency, and its mechanism may be different from those of warfarin.