Effect of sodium taurolithocholate on bile flow and bile acid excretion (original) (raw)
Related papers
Digestive Diseases and Sciences, 1994
Taurohyodeoxycholic acid is a natural 6et-hydroxylated bile acid with an apparent hydrophilicity intermediate between those of tauroursodeoxycholic and taurocholic acids. We investigated in the rat the hepatobiliary metabolism, choleretic properties, and biliary maximum secretory rate (SRmax) of taurohyodeoxycholic in comparison with these two bile salts. Each compound was infused intravenously, at a rate increased in a stepwise manner from 100 to 300 nmol/min/100 g body wt, in bile salt-depleted bile fistula rats. The three bile salts appeared rapidly starting with the infusion and increased to represent more than 95% of the total bile salts. No apparent biliary metabolites were formed. All the bile salts caused a dose-dependent increase in bile flow and biliary lipid output. The absolute increase in bile flow was lower in rats infused with taurohyodeoxycholic acid, yet the volume of bile formed per nanomole of secreted bile salt was 13.8 nl for taurohyodeoxycholic, 6.4 nl for tauroursodeoxycholic acid, and 10.9 nl for taurocholic. The SRm~, , values were 1080, 3240, and 960 nmol/min/100 g, respectively. At all infusion rates, taurohyodeoxycholic acid caused a greater (P < 0.001) secretion of biliary lecithin compared to the other bile salts. There were no significant differences in the biliary secretion of cholesterol and proteins. Electron microscopy showed the recruitment of vesicles and lamellar bodies around and within bile canaliculi. In conclusion, taurohyodeoxycholic promotes a biliary lecithin secretion greater than expected from physicochemical predictions, representing a novel secretory property with potential pharmacological relevance.
The effect of taurine depletion with guanidinoethanesulfonate on bile acid metabolism in the rat
Life Sciences, 1985
~dministration of guanidinoethanesulfonate (GES) to male rats for 5 weeks resulted in a 90% decrease in the hepatic taurine concentration. This depletion of hepatic taurine was associated with a 570% increase in the concentration of glycine-conjugated bile acids, a 30 % decrease in the concentration of taurine-conjugated bile acids, and an increase in the ratio of glycine-to taurine-conjugated bile acids from 0.046 to 0.45. The total concentration of bile salts in the bile and the turnover of cholic acid were not affected by administration of GE~ The data indicate that the taurine-depleted rat conserves taurine to some extent by using glycine instead of taurine for bile salt synthesis but not by decreasing the daily fractional turnover of bile acids.
Taurine increases bile acid pool size and reduces bile saturation index in the hamster
Journal of lipid research, 1987
There is evidence that increased availability of taurine enhances the proportion of taurine-conjugated bile acids in bile. To explore the possibility that taurine treatment could also influence hepatic cholesterol and bile acid metabolism, we fed female hamsters for 1 week and measured both the biliary lipid content and the microsomal level of the rate-limiting enzymes of cholesterol and bile acid synthesis. In these animals the cholesterol 7 alpha-hydroxylase activity was significantly greater in respect to controls (P less than 0.05). The total HMG-CoA reductase activity, as well as that of the active form, was similarly increased. The stimulation of 7 alpha-hydroxycholesterol synthesis was associated with an expansion of the bile acid pool size in taurine-fed animals. Taurine feeding was observed to induce an increase in bile flow as well as in the rate of excretion of bile acids, whereas the secretion rate of cholesterol in bile was decreased. As a consequence, the saturation in...
Tauroursodeoxycholic acid for treatment of primary biliary cirrhosis
Digestive Diseases and Sciences, 1996
Tauroursodeoxycholic acid, a highly hydrophilic bile acid, may be of therapeutic value for chronic cholestatic liver diseases. We performed a dose-response study on 24 patients with primary biliary cirrhosis who were randomly assigned to receive 500, 1000, or 1500 mg daily of tauroursodeoxycholic acid for six months. Biliary enrichment with ursodeox)'cholic acid ranged from 15% to 48% and was not related with the dose. Serum liver enzyme levels decreased significantly after the first month of treatment with all the three doses. No significant difference among the three doses was found, although further reduction over time occurred with 1000 and 1500 mg daily. Plasma total and HDL cholesterol significantly decreased in patients administered the two higher doses. Diarrhea was the only side effect. In conclusion, a dose of about 10 m~kg body wt/day of tauroursodeoxycholic acid should be used for long-term studies in patients with primary biliary cirrhosis.
Liver International, 2007
Background: Cholangiopathies impair the balance between proliferation and apoptosis of cholangiocytes leading to the disappearance of bile ducts and liver failure. Taurocholic acid (TC) is essential for cholangiocyte proliferative and functional response to cholestasis. Bile acids and neurotransmitters co-operatively regulate the biological response of the biliary epithelium to cholestasis. Adrenergic denervation of the liver during cholestasis results in the damage of bile ducts. Aim: To verify whether TC feeding prevents the damage of the biliary tree induced by adrenergic denervation in the course of cholestasis. Methods: Rats subjected to bile duct ligation (BDL) and to adrenergic denervation were fed a TC-enriched diet, in the absence or presence of daily administration of the phosphatidylinositol-3-kinase (PI3K) inhibitor wortmannin for 1 week. Results: TC prevented the induction of cholangiocyte apoptosis induced by adrenergic denervation. TC also restored cholangiocyte proliferation and functional activity, reduced after adrenergic denervation. TC prevented AKT dephosphorylation induced by adrenergic denervation. The cytoprotective effects of TC were abolished by the simultaneous administration of wortmannin. Summary/conclusions: TC administration prevents the damage of the biliary tree induced by the adrenergic denervation of the liver. These novel findings open novel perspectives in the understanding of the potential of bile acids especially in post-transplant liver disease.
Comparative Biochemistry and Physiology Part A: Physiology, 1996
Dose-response curves for taurocholate and tauroursodeoxycholate were performed in rat and rabbit livers to get more insight into species differences in the hepatic bile acid uptake. The bile acids showed saturation kinetics in both animals, the V,,, in rat being higher than in rabbit and the K, being lower in the rat than in the rabbit for both the bile acids, with no significant difference in the hepatic cells morphometric parameters. Therefore, it is possible that differences in the kinetic parameters are related to the number and, to a lesser extent, to the affinity of the transporters on the sinusoidal plasma membranes. COMP BIOCHEM PHYSIC),. 113A:2:157-164. 1996.
Metabolism of Taurolithocholic Acid in the Hamster
Journal of Biological Chemistry, 1967
Sodium taurolithocholate-24J*C was infused intravenously into bile fistula hamsters and one rat. More than 95% of the administered l*C was recovered in bile. The bile of the rat contained a variety of metabolites comparable to those lmown to occur after lithocholic acid administration. Only one metabolite, taurochenodeoxycholate-l*C, was identified in hamster bile.
World Journal of Gastroenterology, 2006
AIM: To investigate the effects of taurolithocholate (TLC) on the canalicular motility in isolated rat hepatocyte couplets (IRHC). METHODS: TLC was added to IRHC at concentrations of 10 and 50 μmol/L, respectively. In each group, five time-lapse movies containing 3 representative bile canaliculi were taken under phase-contrast microscopy for 12 h. The number of bile canalicular contractions and the intervals between consecutive canalicular contractions were calculated. Furthermore, the effects of TLC on IRHC were examined by transmission electron microscopy.