Cellular accumulation and toxic effects of bile acids in cyclosporine a-treated hepaRG hepatocytes

Toxicological Sciences

Volumn 147, Issue 2, 2015, Pages 573-587

  Sharanek, Ahmad ^a,b   Burban, Audrey ^a,b   Humbert, Lydie ^c   Bachour El Azzi, Pamela ^a,b   Felix Gomes, Neuza ^c   Rainteau, Dominique ^c   Guillouzo, Andre ^a,b,d,e  

^a Univ Rennes   (France)

^b UNIVERSITÉ DE RENNES 1   (France)

^c SORBONNE UNIVERSITÉ   (France)

^d HÔPITAL SAINT ANTOINE   (France)

^e CNRS   (France)

Author keywords

Cholestasis; Drug induced liver injury; Human hepatocytes; Lithocholic acid; Primary bile acids

Indexed keywords

BILE ACID; CYCLOSPORIN A; CYTOCHROME; SODIUM BILE ACID COTRANSPORTER; CHOLESTANETRIOL 26 MONOOXYGENASE; CHOLESTEROL 7ALPHA MONOOXYGENASE; CYCLOSPORIN; CYP27A1 PROTEIN, HUMAN; CYP7A1 PROTEIN, HUMAN; STEROID 12ALPHA MONOOXYGENASE;

ARTICLE; BILE ACID SYNTHESIS; CHOLESTASIS; CONTROLLED STUDY; CYTOTOXICITY; DOSE RESPONSE; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER CELL; PROTEIN EXPRESSION; CELL LINE; CHEMISTRY; DRUG EFFECTS; GENE EXPRESSION; METABOLISM; WESTERN BLOTTING;

BILE ACIDS AND SALTS; BLOTTING, WESTERN; CELL LINE; CHOLESTANETRIOL 26-MONOOXYGENASE; CHOLESTEROL 7-ALPHA-HYDROXYLASE; CYCLOSPORINE; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION; HEPATOCYTES; HUMANS; STEROID 12-ALPHA-HYDROXYLASE;

EID: 84943800923     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfv155     Document Type: Article

References (48)

1. Alnouti, Y. (2009). Bile acid sulfation: A pathway of bile acid elimination and detoxification. Toxicol. Sci. 108, 225-246.
2. Amundsen, R., Asberg, A., Ohm, I.K., and Christensen, H. (2012). Cyclosporine A- and tacrolimus-mediated inhibition of CYP3A4 and CYP3A5 in vitro. Drug Metab. Dispos. 40, 655-661.
3. Aninat, C., Piton, A., Glaise, D., Le Charpentier, T., Langouet, S., Morel, F., Guguen-Guillouzo, C., and Guillouzo, A. (2006). Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells. Drug Metab. Dispos. 34, 75-83.
4. Antherieu, S., Bachour-El Azzi, P., Dumont, J., Abdel-Razzak, Z., Guguen-Guillouzo, C., Fromenty, B., Robin, M.A., and Guillouzo, A. (2013). Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells. Hepatology 57, 1518-1529.
5. Antherieu, S., Chesne, C., Li, R., Camus, S., Lahoz, A., Picazo, L., Turpeinen, M., Tolonen, A., Uusitalo, J., Guguen-Guillouzo, C., et al. (2010). Stable expression, activity, and inducibility of cytochromes P450 in differentiated HepaRG cells. Drug Metab. Dispos. 38, 516-525.
6. Axelson, M., Ellis, E., Mork, B., Garmark, K., Abrahamsson, A., Bjorkhem, I., Ericzon, B.G., and Einarsson, C. (2000). Bile acid synthesis in cultured human hepatocytes: Support for an alternative biosynthetic pathway to cholic acid. Hepatology 31, 1305-1312.
7. Axelson, M., Mork, B., and Everson, G.T. (1991). Bile acid synthesis in cultured human hepatoblastoma cells. J. Biol. Chem. 266, 17770-17777.
8. Bachour-El Azzi, P., Sharanek, A., Burban, A., Li, R., Guevel, R.L., Abdel-Razzak, Z., Stieger, B., Guguen-Guillouzo, C., and Guillouzo, A. (2015). Comparative localization and functional activity of the main hepatobiliary transporters in HepaRG Cells and primary human hepatocytes. Toxicol. Sci. 145, 157-168.
9. Bjornsson, E.S., and Jonasson J.G. (2013). Drug-induced cholestasis. Clin. Liver Dis. 17, 191-209.
10. Boyer, J.L. (2013). Bile formation and secretion. Compr. Physiol. 3, 1035-1078.
11. Cerec, V., Glaise, D., Garnier, D., Morosan, S., Turlin, B., Drenou, B., Gripon, P., Kremsdorf, D., Guguen-Guillouzo, C., and. Corlu, A.;1. (2007). Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor. Hepatology 45, 957-967.
12. Chiang, J.Y. (2009). Bile acids: Regulation of synthesis. J. Lipid Res. 50, 1955-1966.
13. Dawson, P.A., Lan, T., and Rao, A. (2009). Bile acid transporters. J. Lipid Res. 50, 2340-2357.
14. Einarsson, C., Ellis, E., Abrahamsson, A., Ericzon, B.G., Bjorkhem, I., and Axelson, M. (2000). Bile acid formation in primary human hepatocytes. World J. Gastroenterol. 6, 522-525.
15. Ellis, E., Axelson, M., Abrahamsson, A., Eggertsen, G., Thorne, A., Nowak, G., Ericzon, B.G., Bjorkhem, I., and Einarsson, C. (2003). Feedback regulation of bile acid synthesis in primary human hepatocytes: Evidence that CDCA is the strongest inhibitor. Hepatology 38, 930-938.
16. Ellis, E.C., and Nilsson, L.M. (2010). The use of human hepatocytes to investigate bile acid synthesis. Methods Mol. Biol. 640, 417-430.
17. Ellis, E., Goodwin, B., Abrahamsson, A., Liddle, C., Mode, A., Rudling, M., Bjorkhem, I., and Einarsson, C. (1998). Bile acid synthesis in primary cultures of rat and human hepatocytes. Hepatology 27, 615-620.
18. Everson, G.T., and Polokoff, M.A. (1986). HepG2. A human hepatoblastoma cell line exhibiting defects in bile acid synthesis and conjugation. J. Biol. Chem. 261, 2197-2201.
19. Grattagliano, I., Bonfrate, L., Diogo, C.V., Wang, H.H., Wang, D.Q., and Portincasa, P. (2009). Biochemical mechanisms in drug-induced liver injury: Certainties and doubts. World J. Gastroenterol. 15, 4865-4876.
20. Guguen-Guillouzo, C., and Guillouzo, A. (2010). General review on in vitro hepatocyte models and their applications. Methods Mol. Biol. 640, 1-40.
21. Guguen-Guillouzo, C., Campion, J.P., Brissot, P., Glaise, D., Launois, B., Bourel, M., and Guillouzo, A. (1982). High yield preparation of isolated human adult hepatocytes by enzymatic perfusion of the liver. Cell Biol. Int. Rep. 6, 625-628.
22. Hirohashi, T., Suzuki, H., Takikawa, H., and Sugiyama, Y. (2000). ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). J. Biol. Chem. 275, 2905-2910.
23. Hoekstra, R., Nibourg, G.A., van der Hoeven, T.V., Plomer, G., Seppen, J., Ackermans, M.T., Camus, S., Kulik, W., van Gulik, T.M., Elferink, R.P., et al. (2013). Phase 1 and phase 2 drug metabolism and bile acid production of HepaRG cells in a bioartificial liver in absence of dimethyl sulfoxide. Drug Metab. Dispos. 41, 562-567.
24. Hofmann, A.F. (2004). Detoxification of lithocholic acid, a toxic bile acid: Relevance to drug hepatotoxicity. Drug Metab. Rev. 36, 703-722.
25. Humbert, L., Maubert, M.A., Wolf, C., Duboc, H., Mahe, M., Farabos, D., Seksik, P., Mallet, J.M., Trugnan, G., Masliah, J., et al. (2012). Bile acid profiling in human biological samples: Comparison of extraction procedures and application to normal and cholestatic patients. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 899, 135-145.
26. Josse, R., Aninat, C., Glaise, D., Dumont, J., Fessard, V., Morel, F., Poul, J.M., Guguen-Guillouzo, C., and Guillouzo, A. (2008). Long-term functional stability of human HepaRG hepatocytes and use for chronic toxicity and genotoxicity studies. Drug Metab. Dispos. 36, 1111-1118.
27. Kullak-Ublick, G.A., Stieger, B., and Meier, P.J. (2004). Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 126, 322-342.
28. Lee, W.M. (2003). Drug-induced hepatotoxicity. N. Engl. J. Med. 349, 474-485.
29. Liu, J., Lu, H., Lu, Y.F., Lei, X., Cui, J.Y., Ellis, E., Strom, S.C., and Klaassen, C.D. (2014). Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol. Sci. 141, 538-546.
30. Lucangioli, S.E., Castano, G., Contin, M.D., and Tripodi, V.P. (2009). Lithocholic acid as a biomarker of intrahepatic cholestasis of pregnancy during ursodeoxycholic acid treatment. Ann. Clin. Biochem. 46, 44-49.
31. Marion, T.L., Perry, C.H., St Claire, R.L., III, and Brouwer, K.L. (2012). Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes. Toxicol. Appl. Pharmacol. 261, 1-9.
32. Monte, M.J., Badia, M.D., Serrano, M.A., Sacristan, M.P., Cassio, D., and Marin, J.J. (2001). Predominance of human versus rat phenotype in the metabolic pathways for bile acid synthesis by hybrid WIF-B9 cells. Biochim. Biophys. Acta 1534, 45-55.
33. Morgan, R.E., van Staden, C.J., Chen, Y., Kalyanaraman, N., Kalanzi, J., Dunn, R.T., II, Afshari, C.A., and Hamadeh, H.K. (2013). A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol. Sci. 136, 216-241.
34. Mudaliar S., Henry R. R., Sanyal A. J., Morrow L., Marschall H. U., Kipnes M., Adorini L., Sciacca C.I., Clopton P., Castelloe E., et al. (2013). Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 145,574-582.
35. Myara, A., Cadranel, J.F., Dorent, R., Lunel, F., Bouvier, E., Gerhardt, M., Bernard, B., Ghoussoub, J.J., Cabrol, A., Gandjbakhch, I., et al. (1996). Cyclosporin A-mediated cholestasis in patients with chronic hepatitis after heart transplantation. Eur. J. Gastroenterol. Hepatol. 8, 267-271.
36. Pauli-Magnus, C., Stieger, B., Meier, Y., Kullak-Ublick, G.A., and Meier, P.J. (2005). Enterohepatic transport of bile salts and genetics of cholestasis. J. Hepatol. 43, 342-357.
37. Princen, H.M., Meijer, P., Wolthers, B.G., Vonk, R.J., and Kuipers, F. (1991). Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis. Biochem. J. 275, 501-505.
38. Pikuleva I. A., and Waterman M. R. (2013). Cytochromes P450: Roles in diseases. J. Biol. Chem. 288, 17091-17098.
39. Rogue, A., Lambert, C., Spire, C., Claude, N., and Guillouzo, A. (2012). Interindividual variability in gene expression profiles in human hepatocytes and comparison with HepaRG cells. Drug Metab. Dispos. 40, 151-158.
40. Sharanek, A., Azzi, P.B., Al-Attrache, H., Savary, C.C., Humbert, L., Rainteau, D., Guguen-Guillouzo, C., and Guillouzo, A. (2014). Different dose-dependent mechanisms are involved in early cyclosporine a-induced cholestatic effects in hepaRG cells. Toxicol Sci. 141, 244-253.
41. Sohlenius-Sternbeck, A.K. (2006). Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicol. In Vitro 20, 1582-1586.
42. Stieger, B., Meier, Y., and Meier, P.J. (2007). The bile salt export pump. Pflugers Arch. 453, 611-620.
43. Trauner, M., and Boyer, J.L. (2003). Bile salt transporters: Molecular characterization, function, and regulation. Physiol. Rev. 83, 633-671.
44. Wagner, M., Zollner, G., and Trauner, M. (2009). New molecular insights into the mechanisms of cholestasis. J. Hepatol. 51, 565-580.
45. Woolbright, B.L., Dorko, K., Antoine, D.J., Clarke, J.I., Gholami, P., Li, F., Kumer, S.C., Schmitt, T.M., Forster, J., Fan, F., et al. (2015). Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis. Toxicol. Appl. Pharmacol. 283, 168-177.
46. Xie, W., Radominska-Pandya, A., Shi, Y., Simon, C.M., Nelson, M.C., Ong, E.S., Waxman, D.J., and Evans, R.M. (2001). An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc. Natl. Acad. Sci. U. S. A. 98, 3375-3380.
47. Zelcer, N., Reid, G., Wielinga, P., Kuil, A., van der Heijden, I., Schuetz, J.D., and Borst, P. (2003). Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem. J. 371, 361-367.
48. Zollner, G., Marschall, H.U., Wagner, M., and Trauner, M. (2006). Role of nuclear receptors in the adaptive response to bile acids and cholestasis: Pathogenetic and therapeutic considerations. Mol. Pharm. 3, 231-251.