Metabolism of Bile Acids. III. Metabolism of Chenodeoxycholic Acid

Publisher Website
Google Scholar
Abstract
The metabolism of chenodeoxycholic acid, a therapeutic agent for gallstone dissolution, was examined in rats, hamsters and rabbits. In rat liver, chenodeoxycholic acid was converted into taurochenodeoxycholate, a part of which was converted into tauromuricholate. In the rat colon, these conjugated bile acids were hydrolyzed into the corresponding free bile acids and a considerable part of the free chenodeoxycholic acid and muricholic acid were further metabolized to lithocholic acid and hyodeoxycholic acid, respectively, by the action of microorganisms. Main metabolites excreted in the rat feces were identified as muricholic acid, hyodeoxycholic acid and lithocholic acid. Direct microbial conversion of muricholic acid into hyodeoxycholic acid was established by in vitro experiment in which muricholic acid was incubated with rat feces suspension. Lithocholic acid and its metabolite, 3.alpha.,6.beta.-dihydroxy-5.beta.-cholanoic acid, were not found in the small intestine. Apparently lithocholic acid is poorly absorbed after its formation in the colon. In hamster liver, chenodeoxycholic acid was converted into tauro- and glycochenodeoxycholates. In the hamster intestinal tract, these conjugated bile acids were deconnugated to form chenodeoxycholic acid, which was further metabolized to lithocholic acid. As seen by the double labeled tracer technique using chenodeoxycholic acid [7.beta.-3H, 24-14C], a considerable amount of lithocholic acid was reabsorbed from the hamster colon. The absorbed lithocholic acid was completely rehydroxylated to chenodeoxycholic acid. Lithocholic acid was not circulated in the enterohepatic circulation. In the rabbit colon, chenodeoxycholic acid was metabolized to lithocholic acid, a part of which was reabsorbed and reached the liver. In contrast to the hamster, the absorbed lithocholic acid was not hydroxylated in the rabbit liver and entered into the enterohepatic circulation.