The effects of cholic acid and eight related cholanic acid analogs on bile flow and biliary excretion of bile salts and cholesterol were studied in rabbits. Bile acids were infused intravenously in anesthetized rabbits. In all except hyodeoxycholic or lithocholic acid treated animals increases in bile flow were recorded within 10 minutes during infusion of bile acid-The increase in bile f1ow associated with an increase in bile salt level in bile after cholic acid infusion was observed, however, there were little changes in biliary, cholesterol levels. Bile salt level in bile was not associated with bile flow after chenodeoxycholic acid infusion but the cholesterol level in bile was significantly increased. Ursodeoxycholic acid similarly increased cholesterol but to a lesser extent. Keto-forms of chenodeoxycholic acid were without action. These results indicate that both cholic and chenodeoxycholic acids have the capacity to alter specific biliary excretion of bile components, the former on bile salts and the latter on cholesterol-a precursor of bile acids in bile.
Animal ; Bile/analysis ; Bile/secretion* ; Bile Acids and Salts/administration & dosage ; Bile Acids and Salts/metabolism ; Bile Acids and Salts/pharmacology* ; Bilirubin/analysis ; Cholesterol/analysis ; Cholesterol/metabolism* ; Cholic Acids/analogs & derivatives ; Cholic Acids/analysis ; Female ; Liver/metabolism ; Male ; Rabbits

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.
Tumor Markers, Biological/analysis ; Middle Aged ; Male ; Humans ; Gallbladder Neoplasms/metabolism ; Female ; Cholic Acids/*analysis/metabolism ; Cholelithiasis/metabolism ; Biliary Tract Neoplasms/*chemistry/metabolism ; Aged, 80 and over ; Aged ; Adult ; Adolescent

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin < or = 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.
Tumor Markers, Biological/analysis ; Middle Aged ; Male ; Humans ; Gallbladder Neoplasms/metabolism ; Female ; Cholic Acids/*analysis/metabolism ; Cholelithiasis/metabolism ; Biliary Tract Neoplasms/*chemistry/metabolism ; Aged, 80 and over ; Aged ; Adult ; Adolescent

Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. Obvious liver injuries could be observed in mice after administrated with ET and DB. Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB. Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed. DB proved to be one of the toxic components in Dioscorea bulbifera L. Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01). Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST. It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury. This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.
Animals ; Bile Acids and Salts ; metabolism ; Chemical and Drug Induced Liver Injury ; metabolism ; Cholic Acid ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Dioscorea ; toxicity ; Drugs, Chinese Herbal ; isolation & purification ; toxicity ; Heterocyclic Compounds, 4 or More Rings ; isolation & purification ; toxicity ; Least-Squares Analysis ; Male ; Mice ; Mice, Inbred ICR ; Plants, Medicinal ; toxicity ; Principal Component Analysis ; Rhizome ; toxicity ; Tandem Mass Spectrometry ; methods ; Taurochenodeoxycholic Acid ; metabolism ; Taurocholic Acid ; metabolism ; Taurodeoxycholic Acid ; metabolism