Importance of the Liver for the Antirachitic Efficacy of Vitamin D

Abstract

The mode of action of vitamin D is at present unknown. A new hypothesis was suggested by Gerstenberger 1 which, on the basis of clinical observations, considered that the action of vitamin D was concerned with some function of the liver thus far unknown. The purpose of the investigation reported here was to approach this hypothesis in animal experiments, in order (1) to study the antirachitic efficacy of vitamin D in rachitic rats in which obstructive biliary cirrhosis had been induced or in which liver damage had been caused by the administration of carbon tetrachloride and (2) to learn whether the resulting decreased antirachitic potency of vitamin D was due to the injury to the liver itself or to other circumstances accompanying the experimental conditions.

Steenbock's rachitogenic Ration 2965 was given to rats 3 weeks of age. To induce cirrhosis of the liver, double ligation and transection of the common bile duct was performed 1 to 1 ½ weeks after the diet had been started. To induce liver damage, 0.2 to 0.3 cc. of carbon tetrachloride was given by intramuscular injection every second day for 3 consecutive weeks, starting also 1 to 1 ½ weeks after the rats were placed on the Steenbock ration.

After 3 weeks of the rickets-producing diet (that is, 1 ½ weeks after operation or after beginning of administration of carbon tetrachloride), antirachitic treatment was begun by intramuscular injection of viosterol in oil, Drisdol, or sodium glycerophosphate solution daily for ten consecutive days.

Under these conditions it was found that bile stasis led regularly in 3 weeks to severe obstructive biliary cirrhosis and that the parenteral administration of carbon tetrachloride resulted in severe fatty and parenchymatous degeneration of the liver rather than in cirrhosis.