Current insights in the complexities underlying drug-induced cholestasis

References

• Aizawa Y, Ikemoto I, Kishimoto K, Wada T, Yamazaki H, Ohishi Y, Kiyota H, Furuta N, Suzuki H, Ueda M. 2003. Flutamide-induced hepatic dysfunction in relation to steady-state plasma concentrations of flutamide and its metabolites. Mol Cell Biochem. 252(1–2):149–156.
   PubMed Web of Science ®Google Scholar
• Akita H, Suzuki H, Ito K, Kinoshita S, Sato N, Takikawa H, Sugiyama Y. 2001. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump. Biochim Biophys Acta. 1511:7–16.
   PubMed Web of Science ®Google Scholar
• Aleo MD, Shah F, He K, Bonin PD, Rodrigues AD. 2017. Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) inhibition in predicting drug-induced liver injury using 125 Pharmaceuticals. Chem Res Toxicol. 30:1219–1229.
   PubMed Web of Science ®Google Scholar
• Alnouti Y. 2009. Bile Acid sulfation: a pathway of bile acid elimination and detoxification. Toxicol Sci off J Soc Toxicol. 108:225–246.
   PubMed Web of Science ®Google Scholar
• Alpini G, Glaser SS, Ueno Y, Rodgers R, Phinizy JL, Francis H, Baiocchi L, Holcomb LA, Caligiuri A, LeSage GD. 1999. Bile acid feeding induces cholangiocyte proliferation and secretion: evidence for bile acid-regulated ductal secretion. Gastroenterology. 116:179–186.
   PubMed Web of Science ®Google Scholar
• Alpini G, Ueno Y, Glaser SS, Marzioni M, Phinizy JL, Francis H, Lesage G. 2001. Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes. Hepatol Baltim Md. 34:868–876.
   PubMed Web of Science ®Google Scholar
• Alvarez M, Zabaleta S, Díaz de Otazu R, Galdos J, Bengoa R, García Campos F. 1993. [Droxicam and severe cholestasis]. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig. 84(4):276.
   PubMed Web of Science ®Google Scholar
• Alvaro D, Della Guardia P, Bini A, Gigliozzi A, Furfaro S, La Rosa T, Piat C, Capocaccia L. 1995. Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets. J Clin Invest. 96:665–675.
   PubMed Web of Science ®Google Scholar
• Ansede JH, Smith WR, Perry CH, St Claire RL, Brouwer KR. 2010. An in vitro assay to assess transporter-based cholestatic hepatotoxicity using sandwich-cultured rat hepatocytes. Drug Metab Dispos Biol Fate Chem. 38:276–280.
   PubMed Web of Science ®Google Scholar
• Anwer MS. 2014. Role of protein kinase C isoforms in bile formation and cholestasis. Hepatol Baltim Md. 60:1090–1097.
   PubMed Web of Science ®Google Scholar
• Axelson M, Sjövall J. 1990. Potential bile acid precursors in plasma–possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man. J Steroid Biochem. 36:631–640.
   PubMedGoogle Scholar
• Ballatori N, Li N, Fang F, Boyer JL, Christian WV, Hammond CL. 2009. OST alpha-OST beta: a key membrane transporter of bile acids and conjugated steroids. Front Biosci. 14:2829–2844.
   PubMed Web of Science ®Google Scholar
• Ballatori N, Truong AT. 1992. Glutathione as a primary osmotic driving force in hepatic bile formation. Am J Physiol. 263:G617–624.
   PubMed Web of Science ®Google Scholar
• Banales JM, Prieto J, Medina JF. 2006. Cholangiocyte anion exchange and biliary bicarbonate excretion. WJG. 12:3496–3511.
   PubMed Web of Science ®Google Scholar
• Barbier O, Duran-Sandoval D, Pineda-Torra I, Kosykh V, Fruchart J-C, Staels B. 2003. Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme. J Biol Chem. 278:32852–32860.
   PubMed Web of Science ®Google Scholar
• Bavli D, Prill S, Ezra E, Levy G, Cohen M, Vinken M, Vanfleteren J, Jaeger M, Nahmias Y. 2016. Real-time monitoring of metabolic function in liver-on-chip microdevices tracks the dynamics of mitochondrial dysfunction. Proc Natl Acad Sci USA. 113:E2231–2240.
   PubMed Web of Science ®Google Scholar
• Bell CC, Dankers ACA, Lauschke VM, Sison-Young R, Jenkins R, Rowe C, Goldring CE, Park K, Regan SL, Walker T, et al. 2018. Comparison of Hepatic 2D Sandwich Cultures and 3D Spheroids for long-term toxicity applications: a multicenter study. Toxicol Sci. 162:655–666.
   PubMed Web of Science ®Google Scholar
• Bell CC, Hendriks DFG, Moro SML, Ellis E, Walsh J, Renblom A, Fredriksson Puigvert L, Dankers ACA, Jacobs F, Snoeys J, et al. 2016. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci Rep. 6:25187.
   PubMed Web of Science ®Google Scholar
• Benedetti A, Strazzabosco M, Ng OC, Boyer JL. 1994. Regulation of activity and apical targeting of the Cl-/HCO3- exchanger in rat hepatocytes. Proc Natl Acad Sci USA. 91:792–796.
   PubMed Web of Science ®Google Scholar
• Benjamin SB, Ishak KG, Zimmerman HJ, Grushka A. 1981. Phenylbutazone liver injury: a clinical-pathologic survey of 23 cases and review of the literature. Hepatol Baltim Md. 1(3):255–263.
   PubMed Web of Science ®Google Scholar
• Bentata Pessayre M, Callard P, Delzant G. 1986. [Cholestatic and cytolytic hepatitis and acute kidney failure caused by pirprofen]. Ann Med Interne (Paris). 137(5):445.
   PubMedGoogle Scholar
• Beuers U, Bilzer M, Chittattu A, Kullak-Ublick GA, Keppler D, Paumgartner G, Dombrowski F. 2001. Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver. Hepatol Baltim Md. 33:1206–1216.
   PubMed Web of Science ®Google Scholar
• Blazquez AG, Briz O, Romero MR, Rosales R, Monte MJ, Vaquero J, Macias RIR, Cassio D, Marin J. 2012. Characterization of the role of ABCG2 as a bile acid transporter in liver and placenta. Mol Pharmacol. 81:273–283.
   PubMed Web of Science ®Google Scholar
• Bode KA, Donner MG, Leier I, Keppler D. 2002. Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Biochem Pharmacol. 64:151–158.
   PubMed Web of Science ®Google Scholar
• Bolder U, Trang NV, Hagey LR, Schteingart CD, Ton-Nu HT, Cerrè C, Elferink RP, Hofmann AF. 1999. Sulindac is excreted into bile by a canalicular bile salt pump and undergoes a cholehepatic circulation in rats. Gastroenterology. 117:962–971.
   PubMed Web of Science ®Google Scholar
• Boyer JL. 1978. Mechanisms of chlorpromazine cholestasis: hypersensitivity or toxic metabolite? Gastroenterology. 74(6):1331–1333.
   PubMed Web of Science ®Google Scholar
• Boyer JL. 2013. Bile formation and secretion. Compr Physiol. 3:1035–1078.
   PubMed Web of Science ®Google Scholar
• Boyer JL, Ng OC, Ananthanarayanan M, Hofmann AF, Schteingart CD, Hagenbuch B, Stieger B, Meier PJ. 1994. Expression and characterization of a functional rat liver Na + bile acid cotransport system in COS-7 cells. Am J Physiol. 266:G382–387.
   PubMedGoogle Scholar
• Boyer JL, Trauner M, Mennone A, Soroka CJ, Cai S-Y, Moustafa T, Zollner G, Lee JY, Ballatori N. 2006. Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents. Am J Physiol Gastrointest Liver Physiol. 290:G1124–1130.
   PubMed Web of Science ®Google Scholar
• Bremmelgaard A, Almé B. 1980. Analysis of plasma bile acid profiles in patients with liver diseases associated with cholestasis. Scand J Gastroenterol. 15:593–600.
   PubMed Web of Science ®Google Scholar
• Bull LN, van Eijk MJ, Pawlikowska L, DeYoung JA, Juijn JA, Liao M, Klomp LW, Lomri N, Berger R, Scharschmidt BF, et al. 1998. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet. 18:219–224.
   PubMed Web of Science ®Google Scholar
• Burbank MG, Burban A, Sharanek A, Weaver RJ, Guguen-Guillouzo C, Guillouzo A. 2016. Early alterations of bile canaliculi dynamics and the rho kinase/myosin light chain kinase pathway are characteristics of drug-induced intrahepatic cholestasis. Drug Metab Dispos Biol Fate Chem. 44:1780–1793.
   PubMed Web of Science ®Google Scholar
• Byrne JA, Strautnieks SS, Mieli-Vergani G, Higgins CF, Linton KJ, Thompson RJ. 2002. The human bile salt export pump: characterization of substrate specificity and identification of inhibitors. Gastroenterology. 123:1649–1658.
   PubMed Web of Science ®Google Scholar
• Cario E, Rünzi M, Becker EW, Gröger G, Ali A, Rehbehn K, Goebell H, Layer P. 1996. [Trimethoprim-sulfamethoxazole-induced cholestatic hepatitis. Clinico-immunological demonstration of its allergic origin]. Dtsch Med Wochenschr 1946. 121(5):129–132.
   PubMedGoogle Scholar
• Carlton VEH, Harris BZ, Puffenberger EG, Batta AK, Knisely AS, Robinson DL, Strauss KA, Shneider BL, Lim WA, Salen G, et al. 2003. Complex inheritance of familial hypercholanemia with associated mutations in TJP2 and BAAT. Nat Genet. 34:91–96.
   PubMed Web of Science ®Google Scholar
• Chai J, Cai S-Y, Liu X, Lian W, Chen S, Zhang L, Feng X, Cheng Y, He X, He Y, et al. 2015. Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. J Hepatol. 63:1440–1448.
   PubMed Web of Science ®Google Scholar
• Chatterjee S, Bijsmans I, van Mil SWC, Augustijns P, Annaert P. 2014. Toxicity and intracellular accumulation of bile acids in sandwich-cultured rat hepatocytes: role of glycine conjugates. Toxicol Vitro Int J Publ Assoc BIBRA. 28:218–230.
   PubMed Web of Science ®Google Scholar
• Chatterjee S, Richert L, Augustijns P, Annaert P. 2014. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis. Toxicol Appl Pharmacol. 274:124–136.
   PubMed Web of Science ®Google Scholar
• Chen M, Bisgin H, Tong L, Hong H, Fang H, Borlak J, Tong W. 2014. Toward predictive models for drug-induced liver injury in humans: are we there yet? Biomarkers Med. 8:201–213.
   PubMed Web of Science ®Google Scholar
• Chen M, Qu BX, Chen XL, Hu HH, Jiang HD, Yu LS, Zhou Q, Zeng S. 2016. Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15. Pharm. 71:337–339.
   Google Scholar
• Chen X, Zhang C, Wang H, Xu J, Duan Z-H, Zhang Y, Yu T, Wei W, Xu D-X, Xu J-M. 2009. Altered integrity and decreased expression of hepatocyte tight junctions in rifampicin-induced cholestasis in mice. Toxicol Appl Pharmacol. 240:26–36.
   PubMed Web of Science ®Google Scholar
• Chen J, Zhao K-N, Chen C. 2014. The role of CYP3A4 in the biotransformation of bile acids and therapeutic implication for cholestasis. Ann Transl Med. 2:7.
   PubMedGoogle Scholar
• Cheng Y, Prusoff WH. 1973. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 22:3099–3108.
   PubMed Web of Science ®Google Scholar
• Cherrington NJ, Hartley DP, Li N, Johnson DR, Klaassen CD. 2002. Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrp1, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats. J Pharmacol Exp Ther. 300:97–104.
   PubMed Web of Science ®Google Scholar
• Choi K, Pfund WP, Andersen ME, Thomas RS, Clewell HJ, LeCluyse EL. 2014. Development of 3D dynamic flow model of human liver and its application to prediction of metabolic clearance of 7-ethoxycoumarin. Tissue Eng Part C Methods. 20:641–651.
   PubMed Web of Science ®Google Scholar
• Choucha Snouber L, Bunescu A, Naudot M, Legallais C, Brochot C, Dumas ME, Elena-Herrmann B, Leclerc E. 2013. Metabolomics-on-a-chip of hepatotoxicity induced by anticancer drug flutamide and Its active metabolite hydroxyflutamide using HepG2/C3a microfluidic biochips. Toxicol Sci off J Soc Toxicol. 132:8–20.
   PubMed Web of Science ®Google Scholar
• Concepcion AR, Lopez M, Ardura-Fabregat A, Medina JF. 2013. Role of AE2 for pHi regulation in biliary epithelial cells. Front Physiol. 4:413.
   PubMed Web of Science ®Google Scholar
• Connolly AK, Price SC, Connelly JC, Hinton RH. 1988. Early changes in bile duct lining cells and hepatocytes in rats treated with alpha-naphthylisothiocyanate. Toxicol Appl Pharmacol. 93:208–219.
   PubMed Web of Science ®Google Scholar
• Cuperus FJC, Claudel T, Gautherot J, Halilbasic E, Trauner M. 2014. The role of canalicular ABC transporters in cholestasis. Drug Metab Dispos Biol Fate Chem. 42:546–560.
   PubMed Web of Science ®Google Scholar
• Davis RA, Kern F, Showalter R, Sutherland E, Sinensky M, Simon FR. 1978. Alterations of hepatic Na+,K+-atpase and bile flow by estrogen: effects on liver surface membrane lipid structure and function. Proc Natl Acad Sci USA. 75:4130–4134.
   PubMed Web of Science ®Google Scholar
• Davit-Spraul A, Fabre M, Branchereau S, Baussan C, Gonzales E, Stieger B, Bernard O, Jacquemin E. 2010. ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history. Hepatol Baltim Md. 51:1645–1655.
   PubMed Web of Science ®Google Scholar
• Dawson S, Stahl S, Paul N, Barber J, Kenna JG. 2012. In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans. Drug Metab Dispos Biol Fate Chem. 40:130–138.
   PubMed Web of Science ®Google Scholar
• De Bruyn T, Chatterjee S, Fattah S, Keemink J, Nicolaï J, Augustijns P, Annaert P. 2013. Sandwich-cultured hepatocytes: utility for in vitro exploration of hepatobiliary drug disposition and drug-induced hepatotoxicity. Expert Opin Drug Metab Toxicol. 9:589–616.
   PubMed Web of Science ®Google Scholar
• De Bruyn T, Sempels W, Snoeys J, Holmstock N, Chatterjee S, Stieger B, Augustijns P, Hofkens J, Mizuno H, Annaert P. 2014. Confocal imaging with a fluorescent bile acid analogue closely mimicking hepatic taurocholate disposition. J Pharm Sci. 103:1872–1881.
   PubMed Web of Science ®Google Scholar
• De Bruyn T, van Westen GJP, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP. 2013. Structure-based identification of OATP1B1/3 inhibitors. Mol Pharmacol. 83:1257–1267.
   PubMed Web of Science ®Google Scholar
• Deferm N, Richert L, Van Brantegem P, De Vocht T, Qi B, de Witte P, Bouillon T, Annaert P. 2019. Detection of drug-induced cholestasis potential in sandwich-cultured human hepatocytes. Methods Mol Biol Clifton NJ. 1981:335–350.
   PubMedGoogle Scholar
• de Lima Toccafondo Vieira M, Tagliati CA. 2014. Hepatobiliary transporters in drug-induced cholestasis: a perspective on the current identifying tools. Expert Opin Drug Metab Toxicol. 10:581–597.
   PubMed Web of Science ®Google Scholar
• Denk GU, Kleiss CP, Wimmer R, Vennegeerts T, Reiter FP, Schulz S, Zischka H, Rust C. 2012. Tauro-β-muricholic acid restricts bile acid-induced hepatocellular apoptosis by preserving the mitochondrial membrane potential. Biochem Biophys Res Commun. 424:758–764.
   PubMed Web of Science ®Google Scholar
• Denk GU, Soroka CJ, Takeyama Y, Chen W-S, Schuetz JD, Boyer JL. 2004. Multidrug resistance-associated protein 4 is up-regulated in liver but down-regulated in kidney in obstructive cholestasis in the rat. J Hepatol. 40:585–591.
   PubMed Web of Science ®Google Scholar
• Dertinger S, Dirschmid K, Vogel W, Drexel H. 1998. Immunosuppressive therapy for carbamazepine-induced hypersensitivity syndrome and hepatitis. J Hepatol. 28(2):356–357.
   PubMed Web of Science ®Google Scholar
• Donato MT, López-Riera M, Castell JV, Gómez-Lechón MJ, Jover R. 2016. Both cholestatic and steatotic drugs trigger extensive alterations in the mRNA level of biliary transporters in rat hepatocytes: Application to develop new predictive biomarkers for early drug development. Toxicol Lett. 263:58–67.
   PubMed Web of Science ®Google Scholar
• Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD. 1998. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA. 95:15665–15670.
   PubMed Web of Science ®Google Scholar
• Dunn JC, Yarmush ML, Koebe HG, Tompkins RG. 1989. Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. FASEB J off Publ Fed Am Soc Exp Biol. 3:174–177.
   PubMed Web of Science ®Google Scholar
• Dutczak WJ, Ballatori N. 1994. Transport of the glutathione-methylmercury complex across liver canalicular membranes on reduced glutathione carriers. J Biol Chem. 269:9746–9751.
   PubMed Web of Science ®Google Scholar
• Elferink MGL, Olinga P, van Leeuwen EM, Bauerschmidt S, Polman J, Schoonen WG, Heisterkamp SH, Groothuis G. 2011. Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 253:57–69.
   PubMed Web of Science ®Google Scholar
• Elias E, Iqbal S, Knutton S, Hickey A, Coleman R. 1983. Increased tight junction permeability: a possible mechanism of oestrogen cholestasis. Eur J Clin Invest. 13:383–390.
   PubMed Web of Science ®Google Scholar
• EMA 2012. European Medicines Agency: CPMP/EWP/560/95/Rev. 1 Corr. 2 – Guideline on the Investigation of Drug Interactions 2012. [accessed 2018 Aug 28]. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/07/WC500129606.pdf.
   Google Scholar
• Esteller A. 2008. Physiology of bile secretion. WJG. 14:5641–5649.
   PubMed Web of Science ®Google Scholar
• Everson GT, Polokoff MA. 1986. HepG2. A human hepatoblastoma cell line exhibiting defects in bile acid synthesis and conjugation. J Biol Chem. 261(5):2197–2201.
   PubMed Web of Science ®Google Scholar
• Fabre S, Loubet B, Aberlenc-Murat M, Gervais C, Arich C. 1982. [Cholestatic and cytolytic hepatitis induced by isaxonine]. Therapie. 37(6):671–674.
   PubMed Web of Science ®Google Scholar
• Farver DK, Lavin MN. 1999. Quinine-induced hepatotoxicity. Ann Pharmacother. 33(1):32–34.
   PubMed Web of Science ®Google Scholar
• Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, Meier PJ. 2001. The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: a potential mechanism for hepatic adverse reactions. Clin Pharmacol Ther. 69:223–231.
   PubMed Web of Science ®Google Scholar
• Ferrer A, Buenestado J, Reñé JM, Piñol MC. 1994. [Acute cholestatic hepatitis caused by droxicam]. Aten Primaria. 14(1):583.
   PubMedGoogle Scholar
• Fickert P, Fuchsbichler A, Wagner M, Zollner G, Kaser A, Tilg H, Krause R, Lammert F, Langner C, Zatloukal K, et al. 2004. Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology. 127:261–274.
   PubMed Web of Science ®Google Scholar
• Fok KC, Bell CJ, Read RB, Eckstein RP, Jones BE. 2013. Lumiracoxib-induced cholestatic liver injury. Intern Med J. 43(6):731–732.
   PubMed Web of Science ®Google Scholar
• Fröhling W, Stiehl A. 1976. Bile salt glucuronides: identification and quantitative analysis in the urine of patients with cholestasis. Eur J Clin Invest. 6:67–74.
   PubMed Web of Science ®Google Scholar
• Fu D, Wakabayashi Y, Ido Y, Lippincott-Schwartz J, Arias IM. 2010. Regulation of bile canalicular network formation and maintenance by AMP-activated protein kinase and LKB1. J Cell Sci. 123:3294–3302.
   PubMed Web of Science ®Google Scholar
• Fuchs M. 2003. Bile acid regulation of hepatic physiology: III. Regulation of bile acid synthesis: past progress and future challenges. Am J Physiol Gastrointest Liver Physiol. 284:G551–557.
   PubMed Web of Science ®Google Scholar
• Funk C, Ponelle C, Scheuermann G, Pantze M. 2001. Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: in vivo and in vitro interaction at the canalicular bile salt export pump (Bsep) in the rat. Mol Pharmacol. 59:627–635.
   PubMed Web of Science ®Google Scholar
• Garzel B, Yang H, Zhang L, Huang S-M, Polli JE, Wang H. 2014. The role of bile salt export pump gene repression in drug-induced cholestatic liver toxicity. Drug Metab Dispos. 42:318–322.
   PubMed Web of Science ®Google Scholar
• Geier A, Wagner M, Dietrich CG, Trauner M. 2007. Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration. Biochim Biophys Acta. 1773:283–308.
   PubMed Web of Science ®Google Scholar
• Gimpl G, Klein U, Reiländer H, Fahrenholz F. 1995. Expression of the human oxytocin receptor in baculovirus-infected insect cells: high-affinity binding is induced by a cholesterol-cyclodextrin complex. Biochemistry. 34:13794–13801.
   PubMed Web of Science ®Google Scholar
• Gissen P, Arias IM. 2015. Structural and functional hepatocyte polarity and liver disease. J Hepatol. 63:1023–1037.
   PubMed Web of Science ®Google Scholar
• González-Mariscal L, Tapia R, Chamorro D. 2008. Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta. 1778:729–756.
   PubMed Web of Science ®Google Scholar
• Groen A, Romero MR, Kunne C, Hoosdally SJ, Dixon PH, Wooding C, Williamson C, Seppen J, Van den Oever K, Mok KS, et al. 2011. Complementary functions of the flippase ATP8B1 and the floppase ABCB4 in maintaining canalicular membrane integrity. Gastroenterology141:1927–1937.e1.4.
   PubMed Web of Science ®Google Scholar
• Guo H-L, Hassan HM, Zhang Y, Dong S-Z, Ding P-P, Wang T, Sun L-X, Zhang L-Y, Jiang Z-Z. 2016. Pyrazinamide induced rat cholestatic liver injury through inhibition of fxr regulatory effect on bile acid synthesis and transport. Toxicol Sci. 152:417–428.
   PubMed Web of Science ®Google Scholar
• Hadj-Rabia S, Baala L, Vabres P, Hamel-Teillac D, Jacquemin E, Fabre M, Lyonnet S, De Prost Y, Munnich A, Hadchouel M, et al. 2004. Claudin-1 gene mutations in neonatal sclerosing cholangitis associated with ichthyosis: a tight junction disease. Gastroenterology. 127:1386–1390.
   PubMed Web of Science ®Google Scholar
• Hagenbuch B, Dawson P. 2004. The sodium bile salt cotransport family SLC10. Pflugers Arch. 447:566–570.
   PubMed Web of Science ®Google Scholar
• Hardison WG, Wood CA. 1978. Importance of bicarbonate in bile salt independent fraction of bile flow. Am J Physiol. 235:E158–164.
   PubMed Web of Science ®Google Scholar
• Hare DL, Horowitz JD. 1986. Verapamil hepatotoxicity: a hypersensitivity reaction. Am Heart J. 111(3):610–611.
   PubMed Web of Science ®Google Scholar
• Hashemi E, Till C, Ioannides C. 2000. Stability of cytochrome P450 proteins in cultured precision-cut rat liver slices. Toxicology. 149:51–61.
   PubMed Web of Science ®Google Scholar
• He K, Cai L, Shi Q, Liu H, Woolf TF. 2015. Inhibition of MDR3 Activity in Human Hepatocytes by Drugs Associated with Liver Injury. Chem Res Toxicol. 28(10):1987–1990.
   PubMed Web of Science ®Google Scholar
• Hegde M, Jindal R, Bhushan A, Bale SS, McCarty WJ, Golberg I, Usta OB, Yarmush ML. 2014. Dynamic interplay of flow and collagen stabilizes primary hepatocytes culture in a microfluidic platform. Lab Chip. 14:2033–2039.
   PubMed Web of Science ®Google Scholar
• Hendriks DFG, Fredriksson Puigvert L, Messner S, Mortiz W, Ingelman-Sundberg M. 2016. Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability. Sci Rep. 6:35434.
   PubMed Web of Science ®Google Scholar
• Ho RH, Leake BF, Roberts RL, Lee W, Kim RB. 2004. Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. J Biol Chem. 279:7213–7222.
   PubMed Web of Science ®Google Scholar
• Hofmann AF. 2004. Detoxification of lithocholic acid, a toxic bile acid: relevance to drug hepatotoxicity. Drug Metab Rev. 36:703–722.
   PubMed Web of Science ®Google Scholar
• Horikawa M, Kato Y, Tyson CA, Sugiyama Y. 2003. Potential cholestatic activity of various therapeutic agents assessed by bile canalicular membrane vesicles isolated from rats and humans. Drug Metab Pharmacokinet. 18(1):16–22.
   PubMedGoogle Scholar
• Horn S, Aglas F, Horina JH. 1999. Cholestasis and liver cell damage due to hypersensitivity to erythromycin stearate--recurrence following therapy with erythromycin succinate. Wien Klin Wochenschr. 111(2):76–77.
   PubMed Web of Science ®Google Scholar
• Hyogo H, Tazuma S, Kajiyama G. 2000. Biliary excretory function is regulated by canalicular membrane fluidity associated with phospholipid fatty acyl chains in the bilayer: implications for the pathophysiology of cholestasis. J Gastroenterol Hepatol. 15:887–894.
   PubMed Web of Science ®Google Scholar
• Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y. 2003. Breast cancer resistance protein exports sulfated estrogens but not free estrogens. Mol Pharmacol. 64:610–618.
   PubMed Web of Science ®Google Scholar
• Isotani E, Zhi G, Lau KS, Huang J, Mizuno Y, Persechini A, Geguchadze R, Kamm KE, Stull JT. 2004. Real-time evaluation of myosin light chain kinase activation in smooth muscle tissues from a transgenic calmodulin-biosensor mouse. Proc Natl Acad Sci USA. 101:6279–6284.
   PubMed Web of Science ®Google Scholar
• Iwanaga T, Nakakariya M, Yabuuchi H, Maeda T, Tamai I. 2007. Involvement of bile salt export pump in flutamide-induced cholestatic hepatitis. Biol Pharm Bull. 30(4):739–744.
   PubMed Web of Science ®Google Scholar
• Janvilisri T, Shahi S, Venter H, Balakrishnan L, van VH. 2005. Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 385:419–426.
   PubMed Web of Science ®Google Scholar
• Javitt NB. 1994. Bile acid synthesis from cholesterol: regulatory and auxiliary pathways. FASEB J. 8:1308–1311.
   PubMed Web of Science ®Google Scholar
• Jung D, Elferink MGL, Stellaard F, Groothuis G. 2007. Analysis of bile acid-induced regulation of FXR target genes in human liver slices. Liver Int. 27:137–144.
   PubMed Web of Science ®Google Scholar
• Kanebratt KP, Andersson TB. 2008. Evaluation of HepaRG cells as an in vitro model for human drug metabolism studies. Drug Metab Dispos Biol Fate Chem. 36:1444–1452.
   PubMed Web of Science ®Google Scholar
• Keeffe EB, Blankenship NM, Scharschmidt BF. 1980. Alteration of rat liver plasma membrane fluidity and ATPase activity by chlorpromazine hydrochloride and its metabolites. Gastroenterology. 79:222–231.
   PubMed Web of Science ®Google Scholar
• Keitel V, Burdelski M, Warskulat U, Kühlkamp T, Keppler D, Häussinger D, Kubitz R. 2005. Expression and localization of hepatobiliary transport proteins in progressive familial intrahepatic cholestasis. Hepatol Baltim Md. 41:1160–1172.
   PubMed Web of Science ®Google Scholar
• Kemp DC, Zamek-Gliszczynski MJ, Brouwer K. 2004. Xenobiotics inhibit hepatic uptake and biliary excretion of taurocholate in rat hepatocytes. Toxicol Sci off J Soc Toxicol. 83:207–214.
   PubMed Web of Science ®Google Scholar
• Kim L, Toh Y-C, Voldman J, Yu H. 2007. A practical guide to microfluidic perfusion culture of adherent mammalian cells. Lab Chip. 7:681–694.
   PubMed Web of Science ®Google Scholar
• Kis E, Ioja E, Rajnai Z, Jani M, Méhn D, Herédi-Szabó K, Krajcsi P. 2012. BSEP inhibition: in vitro screens to assess cholestatic potential of drugs. Toxicol Vitro Int J Publ Assoc BIBRA. 26:1294–1299.
   PubMed Web of Science ®Google Scholar
• Kis E, Rajnai Z, Ioja E, Herédi Szabó K, Nagy T, Méhn D, Krajcsi P. 2009. Mouse Bsep ATPase assay: a nonradioactive tool for assessment of the cholestatic potential of drugs. J Biomol Screen. 14:10–15.
   PubMed Web of Science ®Google Scholar
• Klomp LWJ, Vargas JC, van Mil SWC, Pawlikowska L, Strautnieks SS, van Eijk MJT, Juijn JA, Pabón-Peña C, Smith LB, DeYoung JA, et al. 2004. Characterization of mutations in ATP8B1 associated with hereditary cholestasis. Hepatol Baltim Md. 40:27–38.
   PubMed Web of Science ®Google Scholar
• Köck K, Ferslew BC, Netterberg I, Yang K, Urban TJ, Swaan PW, Stewart PW, Brouwer K. 2014. Risk factors for development of cholestatic drug-induced liver injury: inhibition of hepatic basolateral bile acid transporters multidrug resistance-associated proteins 3 and 4. Drug Metab Dispos Biol Fate Chem. 42:665–674.
   PubMed Web of Science ®Google Scholar
• Kojima H, Nies AT, König J, Hagmann W, Spring H, Uemura M, Fukui H, Keppler D. 2003. Changes in the expression and localization of hepatocellular transporters and radixin in primary biliary cirrhosis. J Hepatol. 39:693–702.
   PubMed Web of Science ®Google Scholar
• Kostrubsky VE, Strom SC, Hanson J, Urda E, Rose K, Burliegh J, Zocharski P, Cai H, Sinclair JF, Sahi J. 2003. Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats. Toxicol Sci off J Soc Toxicol. 76:220–228.
   PubMed Web of Science ®Google Scholar
• Kostrubsky SE, Strom SC, Kalgutkar AS, Kulkarni S, Atherton J, Mireles R, Feng B, Kubik R, Hanson J, Urda E, et al. 2006. Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. Toxicol Sci off J Soc Toxicol. 90:451–459.
   PubMed Web of Science ®Google Scholar
• Kruglov EA, Gautam S, Guerra MT, Nathanson MH. 2011. Type 2 inositol 1,4,5-trisphosphate receptor modulates bile salt export pump activity in rat hepatocytes. Hepatol Baltim Md. 54:1790–1799.
   PubMed Web of Science ®Google Scholar
• Kubitz R, Wettstein M, Warskulat U, Häussinger D. 1999. Regulation of the multidrug resistance protein 2 in the rat liver by lipopolysaccharide and dexamethasone. Gastroenterology. 116:401–410.
   PubMed Web of Science ®Google Scholar
• Landry J, Bernier D, Ouellet C, Goyette R, Marceau N. 1985. Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities. J Cell Biol. 101:914–923.
   PubMed Web of Science ®Google Scholar
• Larrey D, Biclet P, Razafimahaleo A, Degott C, Devergie B, Babany G, Mosnier JF, Scoazec JY, Feldmann G, Pessayre D. 1989. [Hepatitis probably caused by exifone (Adlone)]. Gastroenterol Clin Biol. 13(4):397–400.
   PubMedGoogle Scholar
• Lauterburg BH, Smith CV, Todd EL, Mitchell JR. 1985. Pharmacokinetics of the toxic hydrazino metabolites formed from isoniazid in humans. J Pharmacol Exp Ther. 235(3):566–570.
   PubMed Web of Science ®Google Scholar
• Lenzen R, Hruby VJ, Tavoloni N. 1990. mechanism of glucagon choleresis in guinea pigs. Am J Physiol. 259:G736–744.
   PubMedGoogle Scholar
• Li X, Zhong K, Guo Z, Zhong D, Chen X. 2015. Fasiglifam (TAK-875) inhibits hepatobiliary transporters: a possible factor contributing to fasiglifam-induced liver injury. Drug Metab Dispos Biol Fate Chem. 43:1751–1759.
   PubMed Web of Science ®Google Scholar
• Lim Y-P, Kuo S-C, Lai M-L, Huang J-D. 2009. Inhibition of CYP3A4 expression by ketoconazole is mediated by the disruption of pregnane X receptor, steroid receptor coactivator-1, and hepatocyte nuclear factor 4alpha interaction. Pharmacogenet Genomics. 19:11–24.
   PubMed Web of Science ®Google Scholar
• Lin C, Khetani SR. 2016. Advances in Engineered Liver Models for Investigating Drug-Induced Liver Injury. BioMed Res Int. 2016.
   Google Scholar
• López-Morante AJ, Sáez-Royuela F, Díez-Sánchez V, Martín-Lorente JL, Yuguero L, Ojeda C. 1993. Aspirin-induced cholestatic hepatitis. J Clin Gastroenterol. 16(3):270–272.
   PubMed Web of Science ®Google Scholar
• Mahdi ZM, Synal-Hermanns U, Yoker A, Locher KP, Stieger B. 2016. Role of multidrug resistance Protein 3 in antifungal-induced cholestasis. Mol Pharmacol. 90:23–34.
   PubMed Web of Science ®Google Scholar
• Mangelsdorf DJ, Evans RM. 1995. The RXR heterodimers and orphan receptors. Cell. 83:841–850.
   PubMed Web of Science ®Google Scholar
• Martin H, Sarsat J-P, de Waziers I, Housset C, Balladur P, Beaune P, Albaladejo V, Lerche-Langrand C. 2003. Induction of cytochrome P450 2B6 and 3A4 expression by phenobarbital and cyclophosphamide in cultured human liver slices. Pharm Res. 20:557–568.
   PubMed Web of Science ®Google Scholar
• Masyuk AI, LaRusso NF. 2006. Aquaporins in the hepatobiliary system. Hepatol Baltim Md. 43:S75–S81.
   PubMed Web of Science ®Google Scholar
• Megaraj V, Iida T, Jungsuwadee P, Hofmann AF, Vore M. 2010. Hepatobiliary disposition of 3alpha, 6alpha, 7alpha, 12alpha-tetrahydroxy-cholanoyl taurine: a substrate for multiple canalicular transporters. Drug Metab Dispos Biol Fate Chem. 38:1723–1730.
   PubMed Web of Science ®Google Scholar
• Meier Y, Pauli-Magnus C, Zanger UM, Klein K, Schaeffeler E, Nussler AK, Nussler N, Eichelbaum M, Meier PJ, Stieger B. 2006. Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatol Baltim Md. 44:62–74.
   PubMed Web of Science ®Google Scholar
• Meier PJ, Sztul ES, Reuben A, Boyer JL. 1984. Structural and functional polarity of canalicular and basolateral plasma membrane vesicles isolated in high yield from rat liver. J Cell Biol. 98:991–1000.
   PubMed Web of Science ®Google Scholar
• Mennone A, Soroka CJ, Harry KM, Boyer JL. 2010. Role of breast cancer resistance protein in the adaptive response to cholestasis. Drug Metab Dispos Biol Fate Chem. 38:1673–1678.
   PubMed Web of Science ®Google Scholar
• Metz J, Aoki A, Merlo M, Forssmann WG. 1977. Morphological alterations and functional changes of interhepatocellular junctions induced by bile duct ligation. Cell Tissue Res. 182:299–310.
   PubMed Web of Science ®Google Scholar
• van Midwoud PM, Merema MT, Verweij N, Groothuis GMM, Verpoorte E. 2011. Hydrogel embedding of precision-cut liver slices in a microfluidic device improves drug metabolic activity. Biotechnol Bioeng. 108:1404–1412.
   PubMed Web of Science ®Google Scholar
• Milkiewicz P, Chilton AP, Hubscher SG, Elias E. 2003. Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2). Gut. 52:300–303.
   PubMed Web of Science ®Google Scholar
• Mills JC, Stone NL, Erhardt J, Pittman RN. 1998. Apoptotic membrane blebbing is regulated by myosin light chain phosphorylation. J Cell Biol. 140:627–636.
   PubMed Web of Science ®Google Scholar
• Miszczuk GS, Barosso IR, Zucchetti AE, Boaglio AC, Pellegrino JM, Sánchez Pozzi EJ, Roma MG, Crocenzi FA. 2015. Sandwich-cultured rat hepatocytes as an in vitro model to study canalicular transport alterations in cholestasis. Arch Toxicol. 89:979–990.
   PubMed Web of Science ®Google Scholar
• Mita S, Suzuki H, Akita H, Hayashi H, Onuki R, Hofmann AF, Sugiyama Y. 2006. Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab Dispos Biol Fate Chem. 34:1575–1581.
   PubMed Web of Science ®Google Scholar
• Mita S, Suzuki H, Akita H, Stieger B, Meier PJ, Hofmann AF, Sugiyama Y. 2005. Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol. 288:G159–167.
   PubMed Web of Science ®Google Scholar
• Molina H, Azocar L, Ananthanarayanan M, Arrese M, Miquel JF. 2008. Localization of the Sodium-Taurocholate cotransporting polypeptide in membrane rafts and modulation of its activity by cholesterol in vitro. Biochim Biophys Acta. 1778:1283–1291.
   PubMed Web of Science ®Google Scholar
• Morgan RE, Trauner M, van Staden CJ, Lee PH, Ramachandran B, Eschenberg M, Afshari CA, Qualls CW, Lightfoot-Dunn R, Hamadeh HK. 2010. Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci off J Soc Toxicol. 118:485–500.
   PubMed Web of Science ®Google Scholar
• Morgan RE, van Staden CJ, Chen Y, Kalyanaraman N, Kalanzi J, Dunn RT, Afshari CA, Hamadeh HK. 2013. A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci off J Soc Toxicol. 136:216–241.
   PubMed Web of Science ®Google Scholar
• Morrow PL, Hardin NJ, Bonadies J. 1989. Hypersensitivity myocarditis and hepatitis associated with imipramine and its metabolite, desipramine. J Forensic Sci. 34(4):1016–1020.
   PubMed Web of Science ®Google Scholar
• Mottino AD, Cao J, Veggi LM, Crocenzi F, Roma MG, Vore M. 2002. Altered localization and activity of canalicular Mrp2 in estradiol-17beta-D-glucuronide-induced cholestasis. Hepatol Baltim Md. 35:1409–1419.
   PubMed Web of Science ®Google Scholar
• Müllenbach R, Bennett A, Tetlow N, Patel N, Hamilton G, Cheng F, Chambers J, Howard R, Taylor-Robinson SD, Williamson C. 2005. ATP8B1 mutations in British cases with intrahepatic cholestasis of pregnancy. Gut. 54:829–834.
   PubMed Web of Science ®Google Scholar
• Muzzey D, van Oudenaarden A. 2009. Quantitative time-lapse fluorescence microscopy in single cells. Annu Rev Cell Dev Biol. 25:301–327.
   PubMed Web of Science ®Google Scholar
• Nanau RM, Neuman MG. 2010. Ibuprofen-induced hypersensitivity syndrome. Transl Res J Lab Clin Med. 155(6):275–293.
   Google Scholar
• Nguyen KD, Sundaram V, Ayoub WS. 2014. Atypical causes of cholestasis. World J Gastroenterol. 20:9418–9426.
   PubMed Web of Science ®Google Scholar
• Nies AT, Gatmaitan Z, Arias IM. 1996. ATP-dependent phosphatidylcholine translocation in rat liver canalicular plasma membrane vesicles. J Lipid Res. 37:1125–1136.
   PubMed Web of Science ®Google Scholar
• Nies AT, Keppler D. 2007. The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Arch - Eur J Physiol. 453:643–659.
   PubMed Web of Science ®Google Scholar
• Noe J, Hagenbuch B, Meier PJ, St‐Pierre MV. 2001. Characterization of the mouse bile salt export pump overexpressed in the baculovirus system. Hepatology. 33:1223–1231.
   PubMed Web of Science ®Google Scholar
• Ogimura E, Nakagawa T, Deguchi J, Sekine S, Ito K, Bando K. 2017. Troglitazone inhibits bile acid amidation: a possible risk factor for liver injury. Toxicol Sci off J Soc Toxicol. 158:347–355.
   PubMed Web of Science ®Google Scholar
• Olinga P, Schuppan D. 2013. Precision-cut liver slices: a tool to model the liver ex vivo. J Hepatol. 58:1252–1253.
   PubMed Web of Science ®Google Scholar
• Olson H, Betton G, Robinson D, Thomas K, Monro A, Kolaja G, Lilly P, Sanders J, Sipes G, Bracken W, et al. 2000. Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul Toxicol Pharmacol RTP. 32:56–67.
   PubMed Web of Science ®Google Scholar
• Onakpoya IJ, Heneghan CJ, Aronson JK. 2016. Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. BMC Med. 14:10.
   PubMed Web of Science ®Google Scholar
• Oorts M, Baze A, Bachellier P, Heyd B, Zacharias T, Annaert P, Richert L. 2016. Drug-induced cholestasis risk assessment in sandwich-cultured human hepatocytes. Toxicol Vitro Int J Publ Assoc BIBRA. 34:179–186.
   PubMed Web of Science ®Google Scholar
• Oorts M, Richert L, Annaert P. Bosentan alters endo- and exogenous bile acid disposition in sandwich-cultured human hepatocytes.
   Google Scholar
• Oshio C, Phillips MJ. 1981. Contractility of bile canaliculi: implications for liver function. Science. 212:1041–1042.
   PubMed Web of Science ®Google Scholar
• Painter JN, Savander M, Ropponen A, Nupponen N, Riikonen S, Ylikorkala O, Lehesjoki A-E, Aittomäki K. 2005. Sequence variation in the ATP8B1 gene and intrahepatic cholestasis of pregnancy. Eur J Hum Genet. 13:435–439.
   PubMed Web of Science ®Google Scholar
• Parmentier C, Hendriks DFG, Heyd B, Bachellier P, Ingelman-Sundberg M, Richert L. 2018. Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent. Toxicol Lett. 295:187–194.
   PubMed Web of Science ®Google Scholar
• Pauli-Magnus C, Meier PJ. 2006. Hepatobiliary transporters and drug-induced cholestasis. Hepatol Baltim Md. 44:778–787.
   PubMed Web of Science ®Google Scholar
• Pauli-Magnus C, Meier PJ, Stieger B. 2010. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy. Semin Liver Dis. 30:147–159.
   PubMed Web of Science ®Google Scholar
• Paulusma CC, Folmer DE, Ho-Mok KS, de Waart DR, Hilarius PM, Verhoeven AJ, Oude Elferink R. 2007. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity. Hepatol Baltim Md. 47:268–278.
   Web of Science ®Google Scholar
• Paulusma CC, Kothe MJ, Bakker CT, Bosma PJ, van Bokhoven I, van Marle J, Bolder U, Tytgat GN, Oude Elferink RP. 2000. Zonal down-regulation and redistribution of the multidrug resistance protein 2 during bile duct ligation in rat liver. Hepatol Baltim Md. 31:684–693.
   PubMed Web of Science ®Google Scholar
• Paulusma CC, Waart DR, de Kunne C, Mok KS, Elferink R. 2009. Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem. 284:9947–9954.
   PubMed Web of Science ®Google Scholar
• Pedersen JM, Matsson P, Bergström CAS, Hoogstraate J, Norén A, LeCluyse EL, Artursson P. 2013. Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci Off J Soc Toxicol. 136(2):328–343.
   PubMed Web of Science ®Google Scholar
• Perwaiz S, Forrest D, Mignault D, Tuchweber B, Phillip MJ, Wang R, Ling V, Yousef IM. 2003. Appearance of atypical 3 alpha, 6 beta, 7 beta, 12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid in spgp knockout mice. J Lipid Res. 44:494–502.
   PubMed Web of Science ®Google Scholar
• Polgar O, Robey RW, Bates SE. 2008. ABCG2: structure, function and role in drug response. Expert Opin Drug Metab Toxicol. 4:1–15.
   PubMed Web of Science ®Google Scholar
• Pomiersky C, Blaich E. 1985. [Drug-induced hepatitis with cholestasis following therapy with chlormezanone]. Z Gastroenterol. 23(12):684–686.
   PubMed Web of Science ®Google Scholar
• Rabinovitz M, Van Thiel DH. 1992. Hepatotoxicity of nonsteroidal anti-inflammatory drugs. Am J Gastroenterol. 87(12):1696–1704.
   PubMed Web of Science ®Google Scholar
• Rashidi H, Alhaque S, Szkolnicka D, Flint O, Hay DC. 2016. Fluid shear stress modulation of hepatocyte-like cell function. Arch Toxicol. 90:1757–1761.
   PubMed Web of Science ®Google Scholar
• Ray TK, Skipski VP, Barclay M, Essner E, Archibald FM. 1969. lipid composition of rat liver plasma membranes. J Biol Chem. 244:5528–5536.
   PubMed Web of Science ®Google Scholar
• Renwick AB, Watts PS, Edwards RJ, Barton PT, Guyonnet I, Price RJ, Tredger JM, Pelkonen O, Boobis AR, Lake BG. 2000. Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos. 28:1202–1209.
   PubMed Web of Science ®Google Scholar
• Reshetnyak VI. 2006. Concept on the pathogenesis and treatment of primary biliary cirrhosis. WJG. 12:7250–7262.
   PubMed Web of Science ®Google Scholar
• Rigberg LA, Robinson MJ, Espiritu CR. 1976. Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow. JAMA. 235(4):409–410.
   PubMed Web of Science ®Google Scholar
• Rodrigues AD, Lai Y, Cvijic ME, Elkin LL, Zvyaga T, Soars MG. 2014. Drug-induced perturbations of the bile acid pool, cholestasis, and hepatotoxicity: mechanistic considerations beyond the direct inhibition of the bile salt export pump. Drug Metab Dispos Biol Fate Chem. 42:566–574.
   PubMed Web of Science ®Google Scholar
• Roma MG, Crocenzi FA, Mottino AD. 2008. Dynamic localization of hepatocellular transporters in health and disease. World J Gastroenterol. 14:6786–6801.
   PubMed Web of Science ®Google Scholar
• Rost D, Kartenbeck J, Keppler D. 1999. Changes in the localization of the rat canalicular conjugate export pump mrp2 in phalloidin-induced cholestasis. Hepatology. 29:814–821.
   PubMed Web of Science ®Google Scholar
• Saini SPS, Sonoda J, Xu L, Toma D, Uppal H, Mu Y, Ren S, Moore DD, Evans RM, Xie W. 2004. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol. 65:292–300.
   PubMed Web of Science ®Google Scholar
• Sambrotta M, Strautnieks S, Papouli E, Rushton P, Clark BE, Parry DA, Logan CV, Newbury LJ, Kamath BM, Ling S, et al. 2014. Mutations in TJP2 cause progressive cholestatic liver disease. Nat Genet. 46:326–328.
   PubMed Web of Science ®Google Scholar
• Sánchez Garrido A. 2007. [Omeprazole-induced acute cholestatic hepatitis]. Gastroenterol Hepatol. 30(1):54.
   PubMedGoogle Scholar
• Schachter D. 1984. Fluidity and function of hepatocyte plasma membranes. Hepatology Md. 4:140–151.
   PubMed Web of Science ®Google Scholar
• Schrenk D, Gant TW, Preisegger KH, Silverman JA, Marino PA, Thorgeirsson SS. 1993. Induction of multidrug resistance gene expression during cholestasis in rats and nonhuman primates. Hepatol Baltim Md. 17:854–860.
   PubMed Web of Science ®Google Scholar
• Schumacher R, Lobeck H. 1981. [Cholestatic hepatitis with tienilic acid]. Med Welt. 32(12):402–403.
   PubMedGoogle Scholar
• Setchell KD, Dumaswala R, Colombo C, Ronchi M. 1988. Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. J Biol Chem. 263:16637–16644.
   PubMed Web of Science ®Google Scholar
• Sharanek A, Burban A, Burbank M, Le Guevel R, Li R, Guillouzo A, Guguen-Guillouzo C. 2016. Rho-kinase/myosin light chain kinase pathway plays a key role in the impairment of bile canaliculi dynamics induced by cholestatic drugs. Sci Rep. 6:24709.
   PubMed Web of Science ®Google Scholar
• Sharanek A, Burban A, Humbert L, Bachour-El Azzi P, Felix-Gomes N, Rainteau D, Guillouzo A. 2015. Cellular Accumulation and Toxic Effects of Bile Acids in Cyclosporine A-Treated HepaRG Hepatocytes. Toxicol Sci Off J Soc Toxicol. 147(2):573–587.
   PubMed Web of Science ®Google Scholar
• Sharanek A, Burban A, Humbert L, Guguen-Guillouzo C, Rainteau D, Guillouzo A. 2017. Progressive and preferential cellular accumulation of hydrophobic bile acids induced by cholestatic drugs is associated with inhibition of their amidation and sulfation. Drug Metab Dispos. 45:1292–1303.
   PubMed Web of Science ®Google Scholar
• Shoda LKM, Woodhead JL, Siler SQ, Watkins PB, Howell BA. 2014. Linking physiology to toxicity using DILIsym®, a mechanistic mathematical model of drug-induced liver injury. Biopharm Drug Dispos. 35:33–49.
   PubMed Web of Science ®Google Scholar
• Shu N, Hu M, Liu C, Zhang M, Ling Z, Zhang J, Xu P, Zhong Z, Chen Y, Liu L, et al. 2016. Decreased exposure of atorvastatin in diabetic rats partly due to induction of hepatic Cyp3a and Oatp2. Xenobiotica Fate Foreign Compd Biol Syst. 46:875–881.
   PubMed Web of Science ®Google Scholar
• Slijepcevic D, Roscam Abbing RLP, Katafuchi T, Blank A, Donkers JM, van Hoppe S, de Waart DR, Tolenaars D, van der Meer JHM, Wildenberg M, et al. 2017. Hepatic uptake of conjugated bile acids is mediated by both sodium taurocholate cotransporting polypeptide and organic anion transporting polypeptides and modulated by intestinal sensing of plasma bile acid levels in mice. Hepatol Baltim Md. 66:1631–1643.
   PubMed Web of Science ®Google Scholar
• Smith DJ, Gordon ER. 1987. Membrane fluidity and cholestasis. J Hepatol. 5:362–365.
   PubMed Web of Science ®Google Scholar
• Smith KS, Smith PL, Heady TN, Trugman JM, Harman WD, Macdonald TL. 2003. In vitro metabolism of tolcapone to reactive intermediates: relevance to tolcapone liver toxicity. Chem Res Toxicol. 16(2):123–128.
   PubMed Web of Science ®Google Scholar
• Sookoian S, Castaño G, Burgueño A, Gianotti TF, Pirola CJ. 2008. Association of the multidrug-resistance-associated protein gene (ABCC2) variants with intrahepatic cholestasis of pregnancy. J Hepatol. 48:125–132.
   PubMed Web of Science ®Google Scholar
• Sormunen R, Eskelinen S, Lehto VP. 1993. Bile canaliculus formation in cultured HEPG2 cells. Lab Investig J Tech Methods Pathol. 68(6):652–662.
   PubMed Web of Science ®Google Scholar
• Soroka CJ, Lee JM, Azzaroli F, Boyer JL. 2001. Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver. Hepatol Baltim Md. 33:783–791.
   PubMed Web of Science ®Google Scholar
• Starokozhko V, Vatakuti S, Schievink B, Merema MT, Asplund A, Synnergren J, Aspegren A, Groothuis G. 2017. Maintenance of drug metabolism and transport functions in human precision-cut liver slices during prolonged incubation for 5 days. Arch Toxicol. 91:2079–2092.
   PubMed Web of Science ®Google Scholar
• Staudinger JL, Goodwin B, Jones SA, Hawkins-Brown D, MacKenzie KI, LaTour A, Liu Y, Klaassen CD, Brown KK, Reinhard J, et al. 2001. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci USA. 98:3369–3374.
   PubMed Web of Science ®Google Scholar
• Stedman C, Robertson G, Coulter S, Liddle C. 2004. Feed-forward regulation of bile acid detoxification by CYP3A4: studies in humanized transgenic mice. J Biol Chem. 279:11336–11343.
   PubMed Web of Science ®Google Scholar
• Stieger B, Fattinger K, Madon J, Kullak-Ublick GA, Meier PJ. 2000. Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver. Gastroenterology. 118:422–430.
   PubMed Web of Science ®Google Scholar
• Strazzabosco M, Boyer JL. 1996. Regulation of intracellular pH in the hepatocyte: mechanisms and physiological implications. J Hepatol. 24:631–644.
   PubMed Web of Science ®Google Scholar
• Sultan M, Rao A, Elpeleg O, Vaz FM, Abu-Libdeh B, Karpen SJ, Dawson PA. 2017. Organic solute transporter-β (SLC51B) deficiency in two brothers with congenital diarrhea and features of cholestasis. Hepatology. 68:590–598.
   Web of Science ®Google Scholar
• Susukida T, Sekine S, Nozaki M, Tokizono M, Oizumi K, Horie T, Ito K. 2016. Establishment of a drug-induced, bile acid-dependent hepatotoxicity model using HepaRG cells. J Pharm Sci. 105:1550–1560.
   PubMed Web of Science ®Google Scholar
• Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y. 2003. ABCG2 transports sulfated conjugates of steroids and xenobiotics. J Biol Chem. 278:22644–22649.
   PubMed Web of Science ®Google Scholar
• Swift B, Pfeifer ND, Brouwer K. 2010. Sandwich-cultured hepatocytes: an in vitro model to evaluate hepatobiliary transporter-based drug interactions and hepatotoxicity. Drug Metab Rev.42:446–471.
   PubMed Web of Science ®Google Scholar
• Szalowska E, Stoopen G, Groot MJ, Hendriksen PJ, Peijnenburg AA. 2013. Treatment of mouse liver slices with cholestatic hepatotoxicants results in down-regulation of Fxr and its target genes. BMC Med Genomics. 6:39.
   PubMed Web of Science ®Google Scholar
• Takano K, Kojima T, Sawada N, Himi T. 2014. Role of tight junctions in signal transduction: an update. Excli J. 13:1145–1162.
   PubMed Web of Science ®Google Scholar
• Takikawa H, Otsuka H, Beppu T, Seyama Y, Yamakawa T. 1983. Serum concentrations of bile acid glucuronides in hepatobiliary diseases. Digestion. 27:189–195.
   PubMed Web of Science ®Google Scholar
• Teng S, Piquette-Miller M. 2009. Hepatoprotective role of PXR activation and MRP3 in cholic acid-induced cholestasis. Br J Pharmacol. 151:367–376.
   Web of Science ®Google Scholar
• Terelius Y, Figler RA, Marukian S, Collado MS, Lawson MJ, Mackey AJ, Manka D, Qualls CW, Blackman BR, Wamhoff BR, et al. 2016. Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 255:31–44.
   PubMed Web of Science ®Google Scholar
• Trauner M, Arrese M, Soroka CJ, Ananthanarayanan M, Koeppel TA, Schlosser SF, Suchy FJ, Keppler D, Boyer JL. 1997. The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis. Gastroenterology. 113:255–264.
   PubMed Web of Science ®Google Scholar
• Trauner M, Boyer JL. 2003. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev. 83:633–671.
   PubMed Web of Science ®Google Scholar
• Trottier J, Verreault M, Grepper S, Monté D, Bélanger J, Kaeding J, Caron P, Inaba TT, Barbier O. 2006. Human UDP-glucuronosyltransferase (UGT)1A3 enzyme conjugates chenodeoxycholic acid in the liver. Hepatol Baltim Md. 44:1158–1170.
   PubMed Web of Science ®Google Scholar
• Urquhart BL, Tirona RG, Kim RB. 2007. Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol. 47:566–578.
   PubMed Web of Science ®Google Scholar
• Vatakuti S, Olinga P, Pennings JLA, Groothuis G. 2017. Validation of precision-cut liver slices to study drug-induced cholestasis: a transcriptomics approach. Arch Toxicol. 91:1401–1412.
   PubMed Web of Science ®Google Scholar
• Vatakuti S, Schoonen WGEJ, Elferink MLG, Groothuis GMM, Olinga P. 2015. Acute toxicity of CCl4 but not of paracetamol induces a transcriptomic signature of fibrosis in precision-cut liver slices. Toxicol in Vitro. 29:1012–1020.
   PubMed Web of Science ®Google Scholar
• van Tonder JJ, Steenkamp VS, Gulumian M. 2013. Pre-Clinical Assessment of the Potential Intrinsic Hepatotoxicity of Candidate Drugs. New Insights Toxic Drug Test. [accessed 2018 Jul 19]. https://www.intechopen.com/books/new-insights-into-toxicity-and-drug-testing/pre-clinical-assessment-of-the-potential-intrinsic-hepatotoxicity-of-candidate-drugs.
   Google Scholar
• Vaz FM, Ferdinandusse S. 2017. Bile acid analysis in human disorders of bile acid biosynthesis. Mol Aspects Med. 56:10–24.
   PubMed Web of Science ®Google Scholar
• Vinci B, Duret C, Klieber S, Gerbal-Chaloin S, Sa-Cunha A, Laporte S, Suc B, Maurel P, Ahluwalia A, Daujat-Chavanieu M. 2011. Modular bioreactor for primary human hepatocyte culture: medium flow stimulates expression and activity of detoxification genes. Biotechnol J. 6:554–564.
   PubMed Web of Science ®Google Scholar
• Wagner M, Trauner M. 2005. Transcriptional regulation of hepatobiliary transport systems in health and disease: implications for a rationale approach to the treatment of intrahepatic cholestasis. Ann Hepatol. 4:77–99.
   PubMedGoogle Scholar
• Wagner M, Zollner G, Trauner M. 2009. New molecular insights into the mechanisms of cholestasis. J Hepatol. 51:565–580.
   PubMed Web of Science ®Google Scholar
• Wagner M, Fickert P, Zollner G, Fuchsbichler A, Silbert D, Tsybrovskyy O, Zatloukal K, Guo GL, Schuetz JD, Gonzalez FJ, et al. 2003. Role of farnesoid X receptor in determining hepatic ABC transporter expression and liver injury in bile duct-ligated mice. Gastroenterology. 125:825–838.
   PubMed Web of Science ®Google Scholar
• Wang W, Seward DJ, Li L, Boyer JL, Ballatori N. 2001. Expression cloning of two genes that together mediate organic solute and steroid transport in the liver of a marine vertebrate. Proc Natl Acad Sci USA. 98:9431–9436.
   PubMed Web of Science ®Google Scholar
• Watanabe N, Takashimizu S, Kojima S, Kagawa T, Nishizaki Y, Mine T, Matsuzaki S. 2007. Clinical and pathological features of a prolonged type of acute intrahepatic cholestasis. Hepatol Res off J Jpn Soc Hepatol. 37:598–607.
   PubMed Web of Science ®Google Scholar
• Welch MA, Köck K, Urban TJ, Brouwer KLR, Swaan PW. 2015. Toward predicting drug-induced liver injury: parallel computational approaches to identify multidrug resistance protein 4 and bile salt export pump inhibitors. Drug Metab Dispos Biol Fate Chem. 43:725–734.
   PubMed Web of Science ®Google Scholar
• Wessler JD, Grip LT, Mendell J, Giugliano RP. 2013. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol. 61:2495–2502.
   PubMed Web of Science ®Google Scholar
• Whetton AD, Gordon LM, Houslay MD. 1983. Elevated membrane cholesterol concentrations inhibit glucagon-stimulated adenylate cyclase. Biochem J. 210:437–449.
   PubMed Web of Science ®Google Scholar
• Wolking S, Schaeffeler E, Lerche H, Schwab M, Nies AT. 2015. Impact of genetic polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on drug disposition and potential clinical implications: update of the literature. Clin Pharmacokinet. 54:709–735.
   PubMed Web of Science ®Google Scholar
• Woodhead JL, Watkins PB, Howell BA, Siler SQ, Shoda L. 2017. The role of quantitative systems pharmacology modeling in the prediction and explanation of idiosyncratic drug-induced liver injury. Drug Metab Pharmacokinet. 32:40–45.
   PubMed Web of Science ®Google Scholar
• Woolbright BL, Jaeschke H. 2015. Critical factors in the assessment of cholestatic liver injury in vitro. Methods Mol Biol Clifton NJ. 1250:363–376.
   PubMedGoogle Scholar
• Xie W, Radominska-Pandya A, Shi Y, Simon CM, Nelson MC, Ong ES, Waxman DJ, Evans RM. 2001. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci USA. 98:3375–3380.
   PubMed Web of Science ®Google Scholar
• Yang K, Köck K, Sedykh A, Tropsha A, Brouwer K. 2013. An updated review on drug-induced cholestasis: mechanisms and investigation of physicochemical properties and pharmacokinetic parameters. J Pharm Sci. 102:3037–3057.
   PubMed Web of Science ®Google Scholar
• Yang T, Mei H, Xu D, Zhou W, Zhu X, Sun L, Huang X, Wang X, Shu T, Liu J, et al. 2017. Early indications of ANIT-induced cholestatic liver injury: alteration of hepatocyte polarization and bile acid homeostasis. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 110:1–12.
   PubMed Web of Science ®Google Scholar
• Yasumiba S, Tazuma S, Ochi H, Chayama K, Kajiyama G. 2001. Cyclosporin A reduces canalicular membrane fluidity and regulates transporter function in rats. Biochem J. 354:591–596.
   PubMed Web of Science ®Google Scholar
• Yoneyama K. 2001. Three-dimensional visualization and physiologic evaluation of bile canaliculi in the rat liver slice by confocal laser scanning microscopy. Scanning. 23(6):359–365.
   PubMed Web of Science ®Google Scholar
• Yoshikado T, Takada T, Yamamoto T, Yamaji H, Ito K, Santa T, Yokota H, Yatomi Y, Yoshida H, Goto J, et al. 2011. Itraconazole-induced cholestasis: involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4. Mol Pharmacol. 79:241–250.
   PubMed Web of Science ®Google Scholar
• Zhao G, Xu D, Yuan Z, Jiang Z, Zhou W, Li Z, Yin M, Zhou Z, Zhang L, Wang T. 2017. 8-Methoxypsoralen disrupts MDR3-mediated phospholipids efflux and bile acid homeostasis and its relevance to hepatotoxicity. Toxicology. 386:40–48.
   PubMed Web of Science ®Google Scholar
• Zhou L, Pang X, Jiang J, Zhong D, Chen X. 2017. Nimesulide and 4’-Hydroxynimesulide as Bile Acid Transporters Inhibitors Are Contributory Factors for Drug-Induced Cholestasis. Drug Metab Dispos Biol Fate Chem. 45(5):441–448.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Hennenberg M, Trebicka J, Jochem K, Leifeld L, Biecker E, Sauerbruch T, Heller J. 2006. Intrahepatic upregulation of RhoA and Rho-kinase signalling contributes to increased hepatic vascular resistance in rats with secondary biliary cirrhosis. Gut. 55:1296–1305.
   PubMed Web of Science ®Google Scholar
• Zollner G, Fickert P, Silbert D, Fuchsbichler A, Marschall HU, Zatloukal K, Denk H, Trauner M. 2003. Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis. J Hepatol. 38:717–727.
   PubMed Web of Science ®Google Scholar
• Zollner G, Marschall H-U, Wagner M, Trauner M. 2006. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations. Mol Pharmaceutics. 3:231–251.
   PubMed Web of Science ®Google Scholar
• Zollner G, Wagner M, Trauner M. 2010. Nuclear receptors as drug targets in cholestasis and drug-induced hepatotoxicity. Pharmacol Ther. 126:228–243.
   PubMed Web of Science ®Google Scholar