Effect of taurodehydrocholic acid on the hepatic expression of abcg5 and abcg8 and biliary parameters in the fistula rat

Abstract

Introduction: Biliary secretion of phospholipids and cholesterol is mainly dependent on bile-salt secretion although the exact mechanisms involved are not clearly defined. Aims: This study was to investigate the effect of oral administration of taurodehydrocholic acid (TDHC) on cholesterol metabolism. Materials and methods: TDHC was administered orally at a concentration of 10mM twice a day to rats for 7 days in order to mimic the in vivo situation in gallstone patients on bile salt therapy. Bile duct was cannulated and bile was collected for 30 mins on ice and subjected to analysis for total cholesterol, total bilirubin, alkaline phosphatase (ALP) and Gamma glutamyl transferase (GGT). Liver samples were subjected to real time PCR and the gene expression of the adenosine triphosphate-binding cassette transporter heterodimer Abcg5/g8 was determined. Results: TDHC significantly increased the expression of Abcg5 whilst the level of Abcg8 was significantly decreased. No changes in biliary cholesterol, ALP and GGT were observed, however the total bilirubin was significantly increased in the bile of TDHC administered rats. Conclusions: Increased expression of Abcg5 may be one mechanism by which TDHC stimulates the secretion of biliary cholesterol.