Comparative formation of lithocholic acid from chenodeoxycholic and ursodeoxycholic acids in the colon.
The comparative rate of formation of lithocholic acid from chenodeoxycholic acid and its 7 beta epimer, ursodeoxycholic acid, was studied in human subjects and in a rhesus monkey. [24-14C]Chenodeoxycholic acid and [24-14C]ursodeoxycholic acid were incubated in vitro, under anaerobic conditions, in fecal samples from 7 control and 7 asymptomatic gallstone subjects. The incubations were carried out for 0, 0.5, 1, 4, and 12 h. In addition, the labeled precursors were instilled into the colon of 4 asymptomatic gallstone patients and a rhesus monkey in which a bile duct fistula had been created. Radioactive metabolites were analyzed by thin-layer chromatography in the in vitro fecal incubates and in the in vivo colonic aspirates, stool, and bile. The biotransformation of the unlabeled material was analyzed by gas-liquid chromatography in the in vitro incubates and in the in vivo fecal samples of the rhesus monkey. There was no statistical difference between chenodeoxycholic and ursodeoxycholic acids in their rate of biotransformation to lithocholic acid, when the total group of 14 subjects was compared. However, among these 14, a subgroup of 4 subjects (2 controls and 2 with gallstones) was identified in whom the rate of degradation to lithocholic acid was significantly faster for chenodeoxycholic than for ursodeoxycholic acid. Increases in the concentrations of the precursors led to a decrease in the rate, but not a change in the comparative pattern of lithocholic acid formation. At the lower concentrations, the conversion of both bile acids to lithocholic acid was almost complete after 12 h. In the in vivo studies, the formation of lithocholic acid from chenodeoxycholic and ursodeoxycholic acids was comparable both in the 4 human subjects and in the rhesus monkey. The results of this study indicate that, in most cases, the risk of liver damage from lithocholic acid formation should be similar for both epimers. However, there appears to be a small population in which this risk could be higher during chenodeoxycholic acid than during ursodeoxycholic acid treatment due to a more rapid formation of lithocholic acid.
D000328:Adult; D000368:Aged; D000693:Anaerobiosis; D000818:Animals; D001711:Biotransformation; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D002769:Cholelithiasis / Q000378:metabolism; D003106:Colon / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D005243:Feces / Q000032:analysis; D005260:Female; D006801:Humans; D008095:Lithocholic Acid / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000378:metabolism*
D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid