Additive effects of phenobarbital and high protein diet on liver growth in immature male rats

Abstract

Feeding a high-protein diet to immature male rats results within 7 days in significant increases in liver weight and total liver protein. Daily subcutaneous injections of phenobarbital into immature male rats results in an increase in liver weight and total protein, compared to rats fed a 15% protein diet. Immature male rats given both a high-protein diet and injected with phenobarbital show additive increases in liver weight and total protein. The feeding of a high-protein diet, or the injection of phenobarbital each results in increases in hepatocyte mitotic activity in immature male rats. The simultaneous feeding of a high-protein diet and the injection of phenobarbital results in additive effects on hepatocyte mitotic activity. Associated with the increase in liver size and hepatocyte mitotic activity induced by the feeding of a high-protein diet is an increase in the specific activity of ornithine transcarbamylase, a urea cycle enzyme. Aminopyrine demethylase activity, a drug-metabolizing enzyme, is not increased. Marked increase in aminopyrine demethylase activity is however, associated with the increase in liver size produced by the injection of phenobarbital. Ornithine transcarbamylase activity is not increased after phenobarbital treatment. Marked increases in both aminopyrine demethylase and ornithine transcarbamylase activities are associated with the additive increase in liver size produced by the combined treatment with 64% protein diet and phenobarbital. These results suggest that there may be two separate growth compartments in the liver, one which responds to phenobarbital, and one to high-protein diet.