Preventive effects of phylloquinone on hemorrhagic death induced by butylated hydroxytoluene in male rats.
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 mumole/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.
D000818:Animals; D000975:Antioxidants; D002084:Butylated Hydroxytoluene; D003408:Cresols; D004032:Diet; D004305:Dose-Response Relationship, Drug; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D006873:Hydroquinones; D007020:Hypoprothrombinemias / Q000139:chemically induced / Q000517:prevention & control; D007275:Injections, Intravenous; D008297:Male; D010636:Phenols; D011517:Prothrombin Time; D051381:Rats; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000627:therapeutic use*
D000975:Antioxidants; D003408:Cresols; D006873:Hydroquinones; D010636:Phenols; D002084:Butylated Hydroxytoluene; C019359:2,5-di-tert-butylhydroquinone; D010837:Vitamin K 1; C019584:2,4,6-tri-tert-butylphenol