Potential of nor-ursodeoxycholic acid in cholestatic and metabolic disorders

Digestive Diseases

Volumn 33, Issue 3, 2015, Pages 433-439

  Trauner, Michael ^a   Halilbasic, Emina ^a   Claudel, Thierry ^a   Steinacher, Daniel ^a   Fuchs, Claudia ^a   Moustafa, Tarek ^b   Pollheimer, Marion ^c   Krones, Elisabeth ^c   Kienbacher, Christian ^a   Traussnigg, Stefan ^a   Kazemi Shirazi, Lili ^a   Munda, Petra ^a   Hofer, Harald ^a   Fickert, Peter ^c   Paumgartner, Gustav ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITY OF GRAZ   (Austria)

^c MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

Atherosclerosis; Bicarbonate umbrella; Nonalcoholic fatty liver disease; Primary biliary cirrhosis; Primary sclerosing cholangitis

Indexed keywords

NORURSODEOXYCHOLIC ACID; 24-NORURSODEOXYCHOLIC ACID; URSODEOXYCHOLIC ACID;

AUTOPHAGY; BILE DUCT CARCINOMA; BILE DUCT DISEASE; CHOLESTASIS; CONFERENCE PAPER; HUMAN; INFLAMMATORY BOWEL DISEASE; LIVER DISEASE; LIVER INJURY; METABOLIC DISORDER; METABOLISM; MULTICENTER STUDY (TOPIC); NONALCOHOLIC FATTY LIVER; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIMARY BILIARY CIRRHOSIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SCLEROSING CHOLANGITIS; TRANSGENIC MOUSE; ANALOGS AND DERIVATIVES; ANIMAL; BILE DUCT DISEASES; DRUG EFFECTS; LIVER DISEASES; METABOLIC DISEASES; SIGNAL TRANSDUCTION;

ANIMALS; BILE DUCT DISEASES; HUMANS; LIVER DISEASES; METABOLIC DISEASES; SIGNAL TRANSDUCTION; URSODEOXYCHOLIC ACID;

EID: 84930582859     PISSN: 02572753     EISSN: 14219875     Source Type: Journal    
DOI: 10.1159/000371904     Document Type: Conference Paper

References (39)

1. Hofmann AF, Zakko SF, Lira M, et al: Novel biotransformation and physiological properties of norursodeoxycholic acid in humans. Hepatology 2005; 42: 1391-1398.
2. Yoon YB, Hagey LR, Hofmann AF, Gurantz D, Michelotti EL, Steinbach JH: Effect of sidechain shortening on the physiologic properties of bile acids: hepatic transport and effect on biliary secretion of 23-nor-ursodeoxycholate in rodents. Gastroenterology 1986; 90: 837-852.
3. Fickert P, Wagner M, Marschall HU, et al: 24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 2006; 130: 465-481.
4. Beuers U, Hohenester S, de Buy Wenniger LJ, Kremer AE, Jansen PL, Elferink RP: The biliary HCO(3)(-) umbrella: A unifying hypothesis on pathogenetic and therapeutic aspects of fibrosing cholangiopathies. Hepatology 2010; 52: 1489-1496.
5. Halilbasic E, Fiorotto R, Fickert P, et al: Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2-/-mice. Hepatology 2009; 49: 1972-1981.
6. Moustafa T, Fickert P, Magnes C, et al: Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury. Gastroenterology 2012; 142: 140-151 e12.
7. Sato H, Macchiarulo A, Thomas C, et al: Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies. J Med Chem 2008; 51: 1831-1841.
8. Garcia-Rodriguez JL, Barbier-Torres L, Fernandez-Alvarez S, et al: SIRT1 controls liver regeneration by regulating bile acid metabolism through farnesoid X receptor and mammalian target of rapamycin signaling. Hepatology 2014; 59: 1972-1983.
9. Halilbasic E, Baghdasaryan A, Trauner M: Nuclear receptors as drug targets in cholestatic liver diseases. Clin Liver Dis 2013; 17: 161-189.
10. Hofmann AF: Current concepts of biliary secretion. Dig Dis Sci 1989; 34: 16S-20S.
11. Cohen BI, Hofmann AF, Mosbach EH, et al: Differing effects of nor-ursodeoxycholic or ursodeoxycholic acid on hepatic histology and bile acid metabolism in the rabbit. Gastroenterology 1986; 91: 189-197.
12. Bolder U, Trang NV, Hagey LR, et al: Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats. Gastroenterology 1999; 117: 962-971.
13. Leuschner M, Holtmeier J, Ackermann H, Leuschner U: The influence of sulindac on patients with primary biliary cirrhosis that responds incompletely to ursodeoxycholic acid: A pilot study. Eur J Gastroenterol Hepatol 2002; 14: 1369-1376.
14. Fickert P, Pollheimer MJ, Silbert D, et al: Differential effects of norUDCA and UDCA in obstructive cholestasis in mice. J Hepatol 2013; 58: 1201-1208.
15. Moustafa T, Halilbasic E, Fickert P, et al: Side chain modified bile acids modulate endoplasmic reticulum stress in Mdr2-/-mice in vivo and bile duct epithelial cells in vitro. J Hepatol 2008; 48:S54-S55.
16. Halilbasic E, Claudel T, Bachhofner N, Kapusta C, Trauner M: Norursodeoxycholic acid modulates LPS-induced inflammatory response by interfering with NF?B signalling pathway. J Hepatol 2012; 56:S140.
17. Denk GU, Maitz S, Wimmer R, et al: Conjugation is essential for the anticholestatic effect of NorUrsodeoxycholic acid in taurolithocholic acid-induced cholestasis in rat liver. Hepatology 2010; 52: 1758-1768.
18. Lindor KD, Therneau TM, Jorgensen RA, Malinchoc M, Dickson ER: Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis. Gastroenterology 1996; 110: 1515-1518.
19. Pares A, Caballeria L, Rodes J: Excellent longterm survival in patients with primary biliary cirrhosis and biochemical response to ursodeoxycholic acid. Gastroenterology 2006; 130: 715-720.
20. European Association for the Study of the Liver: EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009; 51: 237-267.
21. Baghdasaryan A, Jha P, Muller M, et al: Inhibition of intestinal bile acid absorption by ASBT inhibitor A4250 protects against bile acid-mediated cholestatic liver injury in mice. J Hepatol 2014; 60:S57.
22. Sombetzki M, Fuchs CD, Fickert P, et al: 24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis. J Hepatol 2014, 2015;62:871-878.
23. Trauner M, Fickert P, Halilbasic E, Moustafa T: Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases. Wien Med Wochenschr 2008; 158: 542-548.
24. Fiorotto R, Scirpo R, Trauner M, et al: Loss of CFTR affects biliary epithelium innate immunity and causes TLR4-NF-B-mediated inflammatory response in mice. Gastroenterology 2011; 141: 1498-1508.
25. Krones E, Pollheimer MJ, Deutschmann A, et al: norUDCA ameliorates cholemic nephropathy in long term common bile duct ligated mice. J Hepatol 2013; 58:S43.
26. Leuschner UF, Lindenthal B, Herrmann G, et al: High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: A doubleblind, randomized, placebo-controlled trial. Hepatology 2010; 52: 472-479.
27. Lindor KD, Kowdley KV, Heathcote EJ, et al: Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology 2004; 39: 770-778.
28. Ratziu V, de Ledinghen V, Oberti F, et al: A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis. J Hepatol 2011; 54: 1011-1019.
29. Mueller M, Thorell A, Claudel T, Jha P, Koefeler H, Lackner C, Hoesel B, Fauler G, Stojakovic T, Einarsson C, Marschall H-U, Trauner M: Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J Hepatol 2015, Epub ahead of print.
30. Mudaliar S, Henry RR, Sanyal AJ, et al: Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type diabetes and nonalcoholic fatty liver disease. Gastroenterology 2013; 145: 574-582. e1.
31. Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al: Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): A multicentre, randomised, placebo-controlled trial. Lancet 2014, Epub ahead of print.
32. Fickert P, Moustafa T, Trauner M: Primary sclerosing cholangitis-the arteriosclerosis of the bile duct? Lipids Health Dis 2007; 6: 3.
33. Fickert P, Moustafa T, Fuchsbichler A, Claudel T, Halilbasic E, Zatloukal K, Denk H, Trauner M: Differential effects of norUDCA and UDCA in the treatment of fatty liver and arteriosclerosis in western chow-fed ApoE knock out mice. J Hepatol 2008; 48(suppl 2):S42.
34. Trauner M, Claudel T, Fickert P, Moustafa T, Wagner M: Bile acids as regulators of hepatic lipid and glucose metabolism. Dig Dis 2010; 28: 220-224.
35. Beraza N, Ofner-Ziegenfuss L, Ehedego H, Boekschoten M, Bischoff SC, Mueller M, Trauner M, Trautwein C: Nor-ursodeoxycholic acid reverses hepatocyte-specific NEMO-dependent steatohepatitis. Gut 2011; 60: 387-396.
36. Lonardo A, Ballestri S, Targher G, Loria P: Diagnosis and management of cardiovascular risk in nonalcoholic fatty liver disease. Expert Rev Gastroenterol Hepatol 2014; 20: 1-22.
37. Teckman J, Fickert P, Trauner M: Autophagy is induced by the bile acid norUDCA, which may be a potential therapy for alpha-1-antitrypsin deficiency Hepatology 2013; 58: 257A-257A.
38. Trauner M, Halilbasic E, Kazemi-Shirazi L, Kienbacher C, Staufer K, Traussnigg S, Hofer H: Therapeutic role of bile acids and nuclear receptor agonists in fibrosing cholangiopathies. Dig Dis 2014; 32: 631-636.
39. Trauner M, Halilbasic E, Baghdasaryan A, Moustafa T, Krones E, Fickert P, Hofer H, Penner E: Primary sclerosing cholangitis: new approaches to diagnosis, surveillance and treatment. Dig Dis 2012; 30(suppl 1):39-47.