Recommended Conferences

Cancer-Treatment and Therapeutics

New York, USA
Related Subjects
 

Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health

Author(s): Dilger K, Hohenester S, Winkler-Budenhofer U, Bastiaansen BAJ, Schaap FG, Rust C, et al

Abstract

Background & Aims Ursodeoxycholic acid (UDCA) exerts anticholestatic, antifibrotic and antiproliferative effects in primary biliary cirrhosis (PBC) via mechanisms not yet fully understood. Its adequate biliary enrichment is considered mandatory for therapeutic efficacy. However, precise determination of biliary enrichment of UDCA is not possible in clinical practice. Therefore, we investigated (i) the relationship between biliary enrichment and plasma pharmacokinetics of UDCA, (ii) the effect of UDCA on plasma and biliary bile acid composition and conjugation patterns, and (iii) on the intestinal detoxification machinery in patients with PBC and healthy controls. Methods In 11 PBC patients and 11 matched healthy subjects, cystic bile and duodenal tissue were collected before and after 3 weeks of administration of UDCA (15 mg/kg/day). Extensive pharmacokinetic profiling of bile acids was performed. The effect of UDCA on the intestinal detoxification machinery was studied by quantitative PCR and Western blotting. Results The relative fraction of UDCA and its conjugates in plasma at trough level[x] correlated with their biliary enrichment[y] (r = 0.73, p = 0.0001, y = 3.65 + 0.49x). Taurine conjugates of the major hydrophobic bile acid, chenodeoxycholic acid, were more prominent in bile of PBC patients than in that of healthy controls. Biliary bile acid conjugation patterns normalized after treatment with UDCA. UDCA induced duodenal expression of key export pumps, BCRP and P-glycoprotein. Conclusions Biliary and trough plasma enrichment of UDCA are closely correlated in PBC and health. Taurine conjugation may represent an adaptive mechanism in PBC against chenodeoxycholic acid-mediated bile duct damage. UDCA may stabilize small intestinal detoxification by upregulation of efflux pumps.

Similar Articles

Gut microbiota role in dietary protein metabolism and health-related outcomes: The two sides of the coin

Author(s): Portune KJ, Beaumont M, Davila AM, Tomé D, Blachier F, Sanz Y

Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells

Author(s): Ignacio BJ, Olmo N, Perez-Ramos P, Santiago-Gómez A, Lecona E, Turnay J, et al

Intestinal bile acid physiology and pathophysiology

Author(s): Martínez-Augustin O, Sánchez de Medina F

Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis

Author(s): Martínez-Moya P, Romero-Calvo I, Requena P, Hernández-Chirlaque C, Aranda CJ, González R, et al

Bile acids as carcinogens in human gastrointestinal cancers

Author(s): Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garewal H

Bile acids regulate intestinal cell proliferation by modulating EGFR and FXR signaling

Author(s): Dossa AY, Escobar O, Golden J, Frey MR, Ford HF, Gayer CP

A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis

Author(s): Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, et al

Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function

Author(s): Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IP, et al

Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome

Author(s): Duboc H, Rainteau D, Rajca S, Humbert L, Farabos D, Maubert M, et al

Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases

Author(s): Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, et al