Ursodeoxycholic acid, chenodeoxycholic acid, and 7-ketolithocholic acid are primary bile acids of the guinea pig.

Gs Tint,Gr Xu,Ak Batta,S Shefer,W Niemann,G Salen

doi:10.1016/s0022-2275(20)42639-2

Abstract

Guinea pig gallbladder bile contains chenodeoxycholic acid (62 +/- 5%), ursodeoxycholic acid (8 +/- 5%), and 7-ketolithocholic acid (30 +/- 5%). All three bile acids became labeled to the same specific activity within 30 min after [3H]cholesterol was injected into bile fistula guinea pigs. When a mixture of [3H]ursodeoxycholic acid and [14C]chenodeoxycholic acid was infused into another bile fistula guinea pig, little 3H could be detected in either chenodeoxycholic acid or 7-ketolithocholic acid. But, 14C was efficiently incorporated into ursodeoxycholic and 7-ketolithocholic acids. Monohydroxylated bile acids make up 51% and ursodeoxycholic acid 38% of fecal bile acids. After 3 weeks of antibiotic therapy, lithocholic acid was reduced to 6% of the total, but ursodeoxycholic acid (5-11%) and 7-ketolithocholic (15-21%) acid persisted in bile. Lathosterol constituted 19% of skin sterols and was detected in the feces of an antibiotic-fed animal. After one bile fistula guinea pig suffered a partial biliary obstruction, ursodeoxycholic and 7-ketolithocholic acids increased to 46% and 22% of total bile acids, respectively. These results demonstrate that chenodeoxycholic acid, ursodeoxycholic acid, and 7-ketolithocholic acid can all be made in the liver of the guinea pig.

Highlights

* * lic acid (62 5%), ursodeoxycholic acid (8 5%), and 7* ketolithocholic acid (30 5%)
After 3 weeks of antibiotic therapy the relative concentration of the lithocholic acids fell to 6 % of total fecal bile acids while chenodiol, ursodiol, and 7-ketolithocholic acid increased to 15%, 68%, and 11%, respectively
Ursodiol, and 7-ketolithocholic acid became labeled to the same extent when [3H]cholesterol was injected into bile fistula guinea pigs (Fig. 2)

Summary

MATERIALS AND METHODS

Radioactive compounds [24-‘‘C]Chenodeoxycholic acid (52 mCi/mmol), [14123H]ursodeoxycholic acid (37 Ci/mmol), and [1,2-3H]cholesterol (50 CVmmol) were purchased from NEN Research Products, Boston, MA. The ability of the liver of the guinea pig to convert cholesterol to chenodiol, ursodiol, and 7-ketolithocholic acid was evaluated by injecting 5.9 pCi of [3H]cholesterol into thej_ug_ular vein of three animals (two control and one antibiotic-fed) immediately after cannulating the bile duct. We investigated the possibility that chenodiol might be transformed to ursodiol and 7-keto1ithocho1ic acid and that ursodiol could be converted to chenodiol and 7-ketolithoc~o~aicid hepatically by injecting 4.5 p c i ["C]chenodiol plus 8.0 pCi [3H]ursodiol into an animal immediately after preparing the bile fistula. In both experiments, bile was collected hourly and the specific activities of each of the three bile acids were measured. All animal experiments were approved by the Animal Research Committees of the VA Medical Center, East Orange, NJ and the New Jersey Medical School, Newark, NJ

RESULTS

Findings

DISCUSSION