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Journal of Nutrition Vol. 109 No. 3 March 1979, pp. 453-457
Copyright © 1979 by American Society for Nutrition
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Preventive Effects of Phylloquinone on Hemorrhagic Death Induced by Butylated Hydroxytoluene in Male Rats1

Osamu Takahashi and Kogo Hiraga

Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Hyakunincho 3 chome, Tokyo 160, Japan

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.

KEY WORDS: • BHT • hemorrhagic death • vitamin K • prothrombin • antioxidant • rats

1 Some of the results of this study were reported at the 51st annual meeting of Japanese Pharmacological Society, Sendai, March, 1978.

Manuscript received 1 June 1978.




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