Effect of taurohyodeoxycholic acid on biliary lipid secretion in humans.
This study aimed to determine the effect in humans of taurohyodeoxycholic acid, a 6alpha-hydroxylated bile acid with hydrophilic properties, on bile lipid secretion. Four cholecystectomized patients who had gallstones and an interrupted enterohepatic circulation were intraduodenally infused with taurohyodeoxycholic and tauroursodeoxycholic acids on separate occasions at a dose of 0.8 to 1 g/h for 3 hours. In hourly bile samples collected for 8 hours after the beginning of the infusion, biliary bile acid composition (by high-performance liquid chromatography), biliary lipid concentrations (by standard methods), and distribution of biliary carriers (by gel chromatography) were evaluated. Blood liver function tests were performed before and after the infusions. Taurohyodeoxycholic and tauroursodeoxycholic acids became the predominant biliary bile acids in all patients except for one infused with taurohyodeoxycholic acid. Taurohyodeoxycholic acid stimulated significantly greater (P < .05) cholesterol and phospholipid secretion per unit of secreted bile acid (0.098 and 0.451 micromol/micromol, respectively) compared with tauroursodeoxycholic acid (0.061 micromol/micromol for cholesterol and 0.275 micromol/micromol for phospholipids). The secretory ratio between phospholipid and cholesterol was significantly higher after infusion of taurohyodeoxycholic acid (3.88 micromol/micromol) compared with taroursodeoxycholic acid (3.09 micromol/micromol) (P < .05). Biliary enrichment with taurohyodeoxycholic acid was positively related with percent concentration of phospholipids but not with that of cholesterol. The opposite trend was observed in tauroursodeoxycholic acid-enriched biles. In both taurohyodeoxycholic acid- and tauroursodeoxycholic acid-rich bile, 80% to 90% of cholesterol was carried in a gel-chromatographic fraction corresponding to an apparent molecular weight of 80 to 200 kd. No alteration in liver function test results was observed after taurohyodeoxycholic acid infusion. In conclusion, taurohyodeoxycholic acid stimulates greater cholesterol and phospholipid secretion than tauroursodeoxycholic acid, but with a higher phospholipid/cholesterol secretory ratio. In bile enriched with both bile acids, biliary cholesterol is transported in non-micellar aggregates. Finally, in the conditions of our study, taurohyodeoxycholic acid was not hepatotoxic.
Loria
P
P
Dipartimento di Medicina Interna, Universita di Modena, Italy.
Bozzoli
M
M
Concari
M
M
Guicciardi
M E
ME
Carubbi
F
F
Bertolotti
M
M
Piani
D
D
Nistri
A
A
Angelico
M
M
Romani
M
M
Carulli
N
N
D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D001646:Bile / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D001647:Bile Acids and Salts / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008111:Liver Function Tests; D008297:Male; D013655:Taurochenodeoxycholic Acid / Q000378:metabolism / Q000494:pharmacology; D013657:Taurodeoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000637:Transaminases / Q000378:metabolism
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; C083510:taurohyodeoxycholic acid; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; C031655:ursodoxicoltaurine; D000637:Transaminases; D000469:Alkaline Phosphatase