Side chain structure determines unique physiologic and therapeutic properties of norUrsodeoxycholic acid in Mdr2-/-mice

Hepatology

Volumn 49, Issue 6, 2009, Pages 1972-1981

  Halilbasic, Emina ^a   Fiorotto, Romina ^b   Fickert, Peter ^a   Marschall, Hanns Ulrich ^c   Moustafa, Tarek ^a   Spirli, Carlo ^b   Fuchsbichler, Andrea ^a   Gumhold, Judith ^a   Silbert, Dagmar ^a   Zatloukal, Kurt ^a   Langner, Cord ^a   Maitra, Uday ^d   Denk, Helmut ^a   Hofmann, Alan F ^e   Strazzabosco, Mario ^b,f,g   Trauner, Michael ^a  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^d INDIAN INSTITUTE OF SCIENCE   (India)

^e UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^f OSPEDALI RIUNITI   (Italy)

^g UNIVERSITY OF MILANO BICOCCA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

24 NORURSODEOXYCHOLIC ACID; ALANINE AMINOTRANSFERASE; ALKALINE PHOSPHATASE; ALPHA SMOOTH MUSCLE ACTIN; BICARBONATE; BILE ACID; CHOLERETIC AGENT; CYTOCHROME P450 2B; CYTOCHROME P450 2B10; CYTOKERATIN 19; DINORURSODEOXYCHOLIC ACID; GLUTATHIONE; HYDROXYPROLINE; MESSENGER RNA; MULTIDRUG RESISTANCE PROTEIN 4; SULFOTRANSFERASE; SULFOTRANSFERASE 2A1; TAURONORURSODEOXYCHOLIC ACID; TAUROURSODEOXYCHOLIC ACID; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID DERIVATIVE;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALKALINE PHOSPHATASE BLOOD LEVEL; AMIDATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE ACID BLOOD LEVEL; BILE COMPOSITION; BILE FLOW; BILE SECRETION; BILIARY TRACT FIBROSIS; CHOLESTATIC LIVER INJURY; CONTROLLED STUDY; DETOXIFICATION; DIET SUPPLEMENTATION; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; HYDROPHILICITY; LIVER FIBROSIS; LIVER HISTOLOGY; LIVER INJURY; LIVER PROTECTION; MALE; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SCLEROSING CHOLANGITIS; STRUCTURE ACTIVITY RELATION;

ANIMALS; CHOLESTASIS, INTRAHEPATIC; MALE; MICE; URSODEOXYCHOLIC ACID;

EID: 68049143345     PISSN: 02709139     EISSN: None     Source Type: Journal    
DOI: 10.1002/hep.22891     Document Type: Article

References (29)

1. Ishibashi H, Komori A, Shimoda S, Gershwin ME. Guidelines for therapy of autoimmune liver disease. Semin Liver Dis 2007;27:214-226.
2. Lazaridis KN, Strazzabosco M, Larusso NF. The cholangiopathies: disorders of biliary epithelia. Gastroenterology 2004;127:1565-1577.
3. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Weiglein AH, Lammert F, et al. Ursodeoxycholic acid aggravates bile infarcts in bile ductligated and Mdr2 knockout mice via disruption of cholangioles. Gastroenterology 2002;123:1238-1251.
4. Fickert P, Fuchsbichler A, Wagner M, Zollner G, Kaser A, Tilg H, et al. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 2004;127:261-274.
5. Trauner M, Fickert P, Wagner M. MDR3 (ABCB4) defects: A paradigm for the genetics of adult cholestatic syndromes. Semin Liver Dis 2007;27: 77-98.
6. Melum E, Boberg KM, Franke A, Bergquist A, Hampe J, Schreiber S, et al. Variation in the MDR3 gene influences disease progression in PSC patients and disease susceptibility in epistatic interaction with polymorphism in OST-alpha gene. HEPATOLOGY 2007;46:265A.
7. Ziol M, Barbu V, Rosmorduc O, Frassati-Biaggi A, Barget N, Hermelin B, et al. ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults. Gastroenterology 2008;135:131-141.
8. Fickert P, Wagner M, Marschall HU, Fuchsbichler A, Zollner G, Tsybrovskyy O, 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.
9. Hofmann AF, Zakko SF, Lira M, Clerici C, Hagey LR, Lambert KK, et al. Novel biotransformation and physiological properties of norursodeoxy-cholic acid in humans. HEPATOLOGY 2005;42:1391-1398.
10. Yoon YB, Hagey LR, Hofmann AF, Gurantz D, Michelotti EL, Steinbach JH. Effect of side-chain 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.
11. Strazzabosco M, Sakisaka S, Hayakawa T, Boyer JL. Effect of UDCA on intracellular and biliary pH in isolated rat hepatocyte couplets and perfused livers. Am J Physiol 1991;260:G58-G69.
12. Fiorotto R, Spirli C, Fabris L, Cadamuro M, Okolicsanyi L, Strazzabosco M. Ursodeoxycholic acid stimulates cholangiocyte fluid secretion in mice via CFTR-dependent ATP secretion. Gastroenterology 2007;133:1603-1613.
13. Snouwaert JN, Brigman KK, Latour AM, Malouf NN, Boucher RC, Smithies O, et al. An animal model for cystic fibrosis made by gene targeting. Science 1992;257:1083-1088.
14. Schteingart CD, Hofmann AF. Synthesis of 24-nor-5 beta-cholan-23-oic acid derivatives: A convenient and efficient one-carbon degradation of the side chain of natural bile acids. J Lipid Res 1988;29:1387-1395.
15. Tserng KY, Hachey DL, Klein PD. An improved procedure for the synthesis of glycine and taurine conjugates of bile acids. J Lipid Res 1977;18: 404-407.
16. Huffman JW, Sobti RR. Synthetic approaches to steroidal alkaloids II (1). Preparation and reactions of 12-oxo-dinorcholanic acids. Steroids 1970; 16:755-770.
17. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Pojer C, Zenz R, et al. Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology 2001;121:170-183.
18. Spirli C, Nathanson MH, Fiorotto R, Duner E, Denson LA, Sanz JM, et al. Proinflammatory cytokines inhibit secretion in rat bile duct epithelium. Gastroenterology 2001;121:156-169.
19. Spirli C, Fabris L, Duner E, Fiorotto R, Ballardini G, Roskams T, et al. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes. Gastroenterology 2003;124:737-753.
20. Mennone A, Alvaro D, Cho W, Boyer JL. Isolation of small polarized bile duct units. Proc Natl Acad Sci U S A 1995;92:6527-6531.
21. Wagner M, Fickert P, Zollner G, Fuchsbichler A, Silbert D, Tsybrovskyy O, t al. Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology 2003;125:825-838.
22. Fickert P, Stoger U, Fuchsbichler A, Moustafa T, Marschall HU, Weiglein AH, et al. A new xenobiotic-induced mouse model of sclerosing cholangitis and biliary fibrosis. Am J Pathol 2007;171:525-536.
23. Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, et al. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology 1997;113:255-264.
24. Jamall IS, Finelli VN, Que Hee SS. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem 1981; 112:70-75.
25. Alpini G, Glaser S, Baiocchi L, Francis H, Xia X, Lesage G. Secretin activation of the apical Na+-dependent bile acid transporter is associated with cholehepatic shunting in rats. HEPATOLOGY 2005;41:1037-1045.
26. Sanchez-Munoz D, Castellano-Megias VM, Romero-Gomez M. Expression of bcl-2 in ductular proliferation is related to periportal hepatic stellate cell activation and fibrosis progression in patients with autoimmune cholestasis. Dig Liver Dis 2007;39:262-266.
27. Clouston AD, Powell EE, Walsh MJ, Richardson MM, Demetris AJ, Jonsson JR. Fibrosis correlates with a ductular reaction in hepatitis C: Roles of impaired replication, progenitor cells and steatosis. HEPATOLOGY 2005; 41:809-818.
28. Zollner G, Marschall HU, Wagner M, Trauner M. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: Pathogenetic and therapeutic considerations. Mol Pharm 2006;3:231-251.
29. Yeh HZ, Schteingart CD, Hagey LR, Ton-Nu HT, Bolder U, Gavrilkina MA, et al. Effect of side chain length on biotransformation, hepatic transport, and choleretic properties of chenodeoxycholyl homologues in the rodent: studies with dinorchenodeoxycholic acid, norchenodeoxycholic acid, and chenodeoxycholic acid. HEPATOLOGY 1997;26:374-385.