Unknown

Dataset Information

0

Effect of bile duct ligation on bile acid composition in mouse serum and liver.


ABSTRACT: Cholestatic liver diseases can be caused by genetic defects, drug toxicities, hepatobiliary malignancies or obstruction of the biliary tract. Cholestasis leads to accumulation of bile acids (BAs) in hepatocytes. Direct toxicity of BAs is currently the most accepted hypothesis for cholestatic liver injury. However, information on which bile acids are actually accumulating during cholestasis is limited.To assess the BA composition in liver and serum after bile duct ligation (BDL) in male C57Bl/6 mice between 6 h and 14 days and evaluate toxicity of the most abundant BAs.Bile acid concentrations increased in liver (27-fold) and serum (1400-fold) within 6 h after surgery and remained elevated up to 14 days. BAs in livers of BDL mice became more hydrophilic than sham controls, mainly because of increased 6?-hydroxylation and taurine conjugation. Among the eight unconjugated and 16 conjugated BAs identified in serum and liver, only taurocholic acid (TCA), ?-muricholic acid (?MCA) and T?MCA were substantially elevated representing >95% of these BAs over the entire time course. Although glycochenodeoxycholic acid and other conjugated BAs increased in BDL animals, the changes were several orders of magnitude lower compared with TCA, ?MCA and T?MCA. A mixture of these BAs did not cause apoptosis or necrosis, but induced inflammatory gene expression in cultured murine hepatocytes.The concentrations of cytotoxic BAs are insufficient to cause hepatocellular injury. In contrast, TCA, ?MCA and T?MCA are able to induce pro-inflammatory mediators in hepatocytes. Thus, BAs act as inflammagens and not as cytotoxic mediators after BDL in mice.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC3263524 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Effect of bile duct ligation on bile acid composition in mouse serum and liver.

Zhang Youcai Y   Hong Ji-Young JY   Rockwell Cheryl E CE   Copple Bryan L BL   Jaeschke Hartmut H   Klaassen Curtis D CD  

Liver international : official journal of the International Association for the Study of the Liver 20111017 1


<h4>Background</h4>Cholestatic liver diseases can be caused by genetic defects, drug toxicities, hepatobiliary malignancies or obstruction of the biliary tract. Cholestasis leads to accumulation of bile acids (BAs) in hepatocytes. Direct toxicity of BAs is currently the most accepted hypothesis for cholestatic liver injury. However, information on which bile acids are actually accumulating during cholestasis is limited.<h4>Aim</h4>To assess the BA composition in liver and serum after bile duct l  ...[more]

Similar Datasets

| S-EPMC6843439 | biostudies-literature
| S-EPMC7458465 | biostudies-literature
2022-05-24 | GSE182049 | GEO
| S-EPMC6057294 | biostudies-literature
| S-EPMC4222180 | biostudies-literature
| S-EPMC3186282 | biostudies-literature
2003-12-13 | GSE898 | GEO
| S-EPMC9930340 | biostudies-literature
| S-EPMC2956779 | biostudies-literature
2009-01-13 | E-GEOD-13747 | biostudies-arrayexpress