Abstract
Bile salts are known to be essential for the absorption of fat-soluble forms of vitamin K from the intestinal tract, but it is not known whether they are of benefit in the absorption of the water-soluble forms. To obtain data regarding this, we have used bile-obstructed rats in which the vitamin K reserves were depleted pre-operatively by the technic previously reported from this laboratory. 1 After ligation of the bile duct, the animals were placed on a diet 2 from which vitamin K was still more rigidly excluded. Within 3-4 days the prothrombin level falls into the bleeding zone. The subsequent rise in prothrombin, following the oral administration of vitamin K, was used as a measure of the extent to which the vitamin is utilized, either with or without supplements of bile salts.
Prothrombin determinations were made by the 2-stage technic of Warner, Brinkhous, and Smith; 3 4 bile salts (1 cc of 3% sodium taurocholate) and vitamin K were given through a metal tube into the stomach. As a source of water-soluble vitamin K, we used the potassium salt of the disulfuric acid ester of 2-methyl-1,4-naphtho-hydroquinone. Since this work was initiated the sodium salt of this compound was described by Fieser. 5 It is apparently somewhat less potent 6 than 2-methyl-1,4-naphthoquinone, when the two compounds are compared on a molar basis. Our own experience indicates that the compound is non-toxic when given orally to rats in doses 100 times the physiological requirements.
Results. Table I shows typical examples of the response of K-deficient rats following administration of daily doses of 2, 5 and 8 μg of the water-soluble compound. It is readily seen that bile salt did not appreciably modify the therapeutic efficacy of the vitamin. At the level of 2 μg, the prothrombin level remained in the bleeding zone.
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