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Metabolism and choleretic activity of homochenodeoxycholic acid in the hamster
Insights
Homochenodeoxycholic acid significantly increases bile production in hamsters, acting as a potent choleretic. It is extensively metabolized into C23 bile acids, including norchenodeoxycholic acid, which contributes to its hypercholeresis.
Area of Science:
- Bile Acid Metabolism
- Hepatology
- Gastroenterology
Background:
- Homochenodeoxycholic acid is a C25 homologue of chenodeoxycholic acid.
- Understanding bile acid metabolism and choleretic effects is crucial for liver function studies.
Purpose of the Study:
- To investigate the hepatic metabolism of homochenodeoxycholic acid.
- To evaluate the choleretic effect of homochenodeoxycholic acid in hamsters.
Main Methods:
- Intravenous administration of 3H-labeled homochenodeoxycholic acid in biliary fistula hamsters.
- Analysis of bile radioactivity and metabolite identification.
- Measurement of bile flow and choleretic activity.
Main Results:
- Over 80% of radioactivity was recovered in bile within 4 hours.
- Significant biotransformation into C23 bile acids occurred, with norchenodeoxycholic acid and its taurine conjugate being major metabolites.
- Homochenodeoxycholic acid induced a pronounced choleresis, with an apparent choleretic activity significantly higher than chenodeoxycholic acid.
Conclusions:
- Homochenodeoxycholic acid is extensively metabolized in the liver, primarily to C23 bile acids.
- It exhibits a potent hypercholeresis, comparable to norchenodeoxycholic acid.
- Hepatic beta-oxidation likely converts homochenodeoxycholic acid to norchenodeoxycholic acid, contributing to its strong choleretic effect.
Abstract:
The hepatic metabolism and the choleretic effect of homochenodeoxycholic acid, the C25 homologue of chenodeoxycholic acid, were investigated in the hamster. After intravenous administration of 3H-labeled homochenodeoxycholic acid into biliary fistula hamsters, more than 80% of the radioactivity was recovered in bile in 4 h. A relatively small proportion of homochenodeoxycholic acid was present in bile as the taurine (22%) or glycine (4%) conjugate. However, more than 70% of the administered compound was biotransformed into C23 bile acids. The major C23 metabolites in bile were norchenodeoxycholic acid (17%), tauronorchenodeoxycholic acid (33%), and a trihydroxy norbile acid (identified as 3 alpha, 5 beta, 7 alpha-trihydroxy-24-nor-5 beta-cholan-23-oic acid, 19%). Small amounts (< 5%) of sulfate(s) and glucuronide(s) were also detected. Homochenodeoxycholic acid, when infused intravenously into the hamster, produced a striking choleresis. The increase in bile flow after infusion of this compound was 6- to 7-times that induced by chenodeoxycholic acid. The apparent choleretic activity of homochenodeoxycholic acid, 181 microliters/mumol, was much greater than that of chenodeoxycholic acid, 11 microliters/mumol. In conclusion, homochenodeoxycholic acid induced a hypercholeresis of the same order of magnitude as norchenodeoxycholic acid, presumably because considerable proportions of this compound were degraded to the hypercholeretic norchenodeoxycholic acid via beta-oxidation in the liver.