Bile acid metabolism in the cirrhotic rat

Bile acid metabolism was studied in rats with cirrhosis induced by carbon tetrachloride (CCl₄). Although the typical histologic features of cirrhosis were seen, cholestasis was not present in these animals as evidenced by a normal total serum bilirubin concentration and by a normal hepatic capacity to remove taurocholate infused intravenously. The cirrhotic rats also secreted taurocholate into bile at a normal rate. The total bile salt pool size in the cirrhotic rats was not significantly different from the pool size in the normal rats (10.59 ± 1.19 μmoles per gm. of liver (±1 standard error of the mean) and 10.43 ± 0.92 μmoles per gm. of liver, respectively). When the bile was drained externally through a chronic bile fistula, the normal rats increased the bile salt synthetic rate approximately 3-fold after 48 hours of drainage. However, the cirrhotic rats failed to significantly increase the synthetic rate for bile salts in response to biliary drainage. The normal rats also had a significant increase in cholic acid synthesis at the maximal synthetic rate, whereas the cirrhotic rats did not. These findings indicate that (when feedback inhibition is removed) CCl₄ cirrhotic rats lack the ability to normally increase the activity of 7α-hydroxylase and 12α-hydroxylase, rate-limiting enzymes in the synthesis of bile salts.