{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:18:14Z","timestamp":1783570694532,"version":"3.55.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T00:00:00Z","timestamp":1547078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"European Community through the Innovative Medicines Initiative Joint Undertaking","award":["115336"],"award-info":[{"award-number":["115336"]}]},{"name":"European Union\u2019s Seventh Framework Programme","award":["FP7\/2007\u20132013"],"award-info":[{"award-number":["FP7\/2007\u20132013"]}]},{"name":"MIP-DILI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"DOI":"10.1093\/toxsci\/kfz009","type":"journal-article","created":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T15:11:05Z","timestamp":1546614665000},"page":"474-485","source":"Crossref","is-referenced-by-count":14,"title":["Predictive Value of Cellular Accumulation of Hydrophobic Bile Acids As a Marker of Cholestatic Drug Potential"],"prefix":"10.1093","volume":"168","author":[{"given":"Audrey","family":"Burban","sequence":"first","affiliation":[{"name":"INSERM U1241, Numecan, Rennes, France"},{"name":"University of Rennes 1, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Sharanek","sequence":"additional","affiliation":[{"name":"INSERM U1241, Numecan, Rennes, France"},{"name":"University of Rennes 1, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydie","family":"Humbert","sequence":"additional","affiliation":[{"name":"ERL INSERM U1157\/UMR7203, Faculty of Medicine Pierre et Marie Curie Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Eguether","sequence":"additional","affiliation":[{"name":"ERL INSERM U1157\/UMR7203, Faculty of Medicine Pierre et Marie Curie Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Guguen-Guillouzo","sequence":"additional","affiliation":[{"name":"INSERM U1241, Numecan, Rennes, France"},{"name":"University of Rennes 1, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Rainteau","sequence":"additional","affiliation":[{"name":"ERL INSERM U1157\/UMR7203, Faculty of Medicine Pierre et Marie Curie Saint Antoine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Guillouzo","sequence":"additional","affiliation":[{"name":"INSERM U1241, Numecan, Rennes, France"},{"name":"University of Rennes 1, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,10]]},"reference":[{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1620\/tjem.185.227","article-title":"Hepatic and serum bile acid compositions in patients with biliary atresia: A microanalysis using gas chromatography-mass spectrometry with negative ion chemical ionization detection","volume":"185","author":"Abukawa","year":"1998","journal-title":"Tohoku J. Exp. Med."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/bdd.293","article-title":"A study of streptomycin blood level information of patients undergoing hemodialysis","volume":"23","author":"Akaho","year":"2002","journal-title":"Biopharm. Drug Dispos."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B3","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1002\/hep.26160","article-title":"Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells","volume":"57","author":"Antherieu","year":"2013","journal-title":"Hepatology"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B4","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/hep.27088","article-title":"Role of protein kinase C isoforms in bile formation and cholestasis","volume":"60","author":"Anwer","year":"2014","journal-title":"Hepatology"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B5","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.freeradbiomed.2017.11.017","article-title":"Endoplasmic reticulum stress precedes oxidative stress in antibiotic-induced cholestasis and cytotoxicity in human hepatocytes","volume":"115","author":"Burban","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B6","doi-asserted-by":"crossref","first-page":"1815.","DOI":"10.1038\/s41598-017-01171-y","article-title":"Penicillinase-resistant antibiotics induce non-immune-mediated cholestasis through HSP27 activation associated with PKC\/P38 and PI3K\/AKT signaling pathways","volume":"7","author":"Burban","year":"2017","journal-title":"Sci. Rep."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B7","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1124\/dmd.116.071373","article-title":"Early alterations of bile canaliculi dynamics and the rho kinase\/myosin light chain kinase pathway are characteristics of drug-induced intrahepatic cholestasis","volume":"44","author":"Burbank","year":"2016","journal-title":"Drug Metab. Dispos."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B8","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/toxsci\/kfx062","article-title":"Mechanistic Insights in cytotoxic and cholestatic potential of the endothelial receptor antagonists using HepaRG cells","volume":"157","author":"Burbank","year":"2017","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B9","doi-asserted-by":"crossref","first-page":"e90780.","DOI":"10.1172\/jci.insight.90780","article-title":"Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response","volume":"2","author":"Cai","year":"2017","journal-title":"JCI Insight"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B10","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1042\/CS20050302","article-title":"Bile acid profiles by capillary electrophoresis in intrahepatic cholestasis of pregnancy","volume":"110","author":"Castano","year":"2006","journal-title":"Clin. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B11","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/hep.21536","article-title":"Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor","volume":"45","author":"Cerec","year":"2007","journal-title":"Hepatology"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B12","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/toxsci\/kfx284","article-title":"Measures of BSEP inhibition in vitro are not useful predictors of DILI","volume":"162","author":"Chan","year":"2018","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B13","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1194\/jlr.R900010-JLR200","article-title":"Bile acids: Regulation of synthesis","volume":"50","author":"Chiang","year":"2009","journal-title":"J. Lipid Res."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B14","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1124\/dmd.111.040758","article-title":"In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans","volume":"40","author":"Dawson","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B15","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1067\/mcp.2001.114667","article-title":"The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: A potential mechanism for hepatic adverse reactions","volume":"69","author":"Fattinger","year":"2001","journal-title":"Clin. Pharmacol. Ther."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0009-8981(96)06305-X","article-title":"Hepatic levels of bile acids in end-stage chronic cholestatic liver disease","volume":"251","author":"Fischer","year":"1996","journal-title":"Clin. Chim. Acta"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2165\/00003088-199732020-00002","article-title":"The clinical pharmacokinetics of levofloxacin","volume":"32","author":"Fish","year":"1997","journal-title":"Clin. Pharmacokinet."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B18","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1136\/hrt.2003.029470","article-title":"Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension","volume":"91","author":"Fukumoto","year":"2005","journal-title":"Heart"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B19","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1194\/jlr.D028803","article-title":"Targeted profiling of circulating and hepatic bile acids in human, mouse, and rat using a UPLC-MRM-MS-validated method","volume":"53","author":"Garcia-Canaveras","year":"2012","journal-title":"J. Lipid Res."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B20","doi-asserted-by":"crossref","first-page":"e0199370.","DOI":"10.1371\/journal.pone.0199370","article-title":"In healthy volunteers, taking flucloxacillin with food does not compromise effective plasma concentrations in most circumstances","volume":"13","author":"Gardiner","year":"2018","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B21","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s002280050350","article-title":"Comparative pharmacokinetics of dirithromycin and erythromycin in normal volunteers with special regard to accumulation in polymorphonuclear leukocytes and in saliva","volume":"53","author":"Geerdes-Fenge","year":"1997","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B22","first-page":"309","volume-title":"Stem Cells in Toxicology and Teratology","author":"Guillouzo","year":"2018"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B23","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.cmet.2017.03.007","article-title":"Farnesoid X receptor regulation of the NLRP3 inflammasome underlies cholestasis-associated sepsis","volume":"25","author":"Hao","year":"2017","journal-title":"Cell Metab."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B24","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1081\/DMR-200033475","article-title":"Detoxification of lithocholic acid, a toxic bile acid: Relevance to drug hepatotoxicity","volume":"36","author":"Hofmann","year":"2004","journal-title":"Drug Metab. Rev."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B25","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jchromb.2012.05.015","article-title":"Bile acid profiling in human biological samples: Comparison of extraction procedures and application to normal and cholestatic patients","volume":"899","author":"Humbert","year":"2012","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B26","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S0016-5085(19)32475-8","article-title":"Scanning electron microscopy of the rat liver. Studies of the effect of taurolithocholate and other models of cholestasis","volume":"69","author":"Layden","year":"1975","journal-title":"Gastroenterology"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1258\/acb.2008.008130","article-title":"Lithocholic acid as a biomarker of intrahepatic cholestasis of pregnancy during ursodeoxycholic acid treatment","volume":"46","author":"Lucangioli","year":"2009","journal-title":"Ann. Clin. Biochem."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B28","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1152\/physrev.00061.2009","article-title":"Hepatocyte death: A clear and present danger","volume":"90","author":"Malhi","year":"2010","journal-title":"Physiol. Rev."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B29","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.cbi.2015.08.016","article-title":"Oxidative stress markers, secondary bile acids and sulfated bile acids classify the clinical liver injury type: Promising diagnostic biomarkers for cholestasis","volume":"255","author":"Masubuchi","year":"2016","journal-title":"Chem. Biol. Interact."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B30","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3748\/wjg.15.804","article-title":"Bile acids: Chemistry, physiology, and pathophysiology","volume":"15","author":"Monte","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B31","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/toxsci\/kfq269","article-title":"Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development","volume":"118","author":"Morgan","year":"2010","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B32","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/00042737-199603000-00015","article-title":"Cyclosporine A-mediated cholestasis in patients with chronic hepatitis after heart transplantation","volume":"8","author":"Myara","year":"1996","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.tiv.2016.03.008","article-title":"Drug-induced cholestasis risk assessment in sandwich-cultured human hepatocytes","volume":"34","author":"Oorts","year":"2016","journal-title":"Toxicol. In Vitro"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B34","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/toxsci\/kft197","article-title":"Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP\/ABCB11)","volume":"136","author":"Pedersen","year":"2013","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B35","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3109\/07853890009011758","article-title":"Bile acids and progesterone metabolites in intrahepatic cholestasis of pregnancy","volume":"32","author":"Reyes","year":"2000","journal-title":"Ann. Med."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B36","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1016\/j.jchromb.2009.09.038","article-title":"Rapid quantification of bile acids and their conjugates in serum by liquid chromatography-tandem mass spectrometry","volume":"877","author":"Scherer","year":"2009","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B37","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/toxsci\/kfu122","article-title":"Different dose-dependent mechanisms are involved in early cyclosporine A-induced cholestatic effects in HepaRG cells","volume":"141","author":"Sharanek","year":"2014","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B38","doi-asserted-by":"crossref","first-page":"24709.","DOI":"10.1038\/srep24709","article-title":"Rho-kinase\/myosin light chain kinase pathway plays a key role in the impairment of bile canaliculi dynamics induced by cholestatic drugs","volume":"6","author":"Sharanek","year":"2016","journal-title":"Sci. Rep."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B39","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/toxsci\/kfv155","article-title":"Cellular accumulation and toxic effects of bile acids in cyclosporine A-treated HepaRG hepatocytes","volume":"147","author":"Sharanek","year":"2015","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B40","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1124\/dmd.117.077420","article-title":"Progressive and preferential cellular accumulation of hydrophobic bile acids induced by cholestatic drugs is associated with inhibition of their amidation and sulfation","volume":"45","author":"Sharanek","year":"2017","journal-title":"Drug Metab. Dispos."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B41","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1002\/phar.2078","article-title":"Serious liver injury associated with macitentan: A case report","volume":"38","author":"Tran","year":"2018","journal-title":"Pharmacotherapy"},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B42","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ajg.2009.633","article-title":"Longitudinal profiles of 15 serum bile acids in patients with intrahepatic cholestasis of pregnancy","volume":"105","author":"Tribe","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B43","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.dld.2011.10.025","article-title":"Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: A pilot study","volume":"44","author":"Trottier","year":"2012","journal-title":"Dig. Liver Dis."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B44","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/toxsci\/kft177","article-title":"Development of an adverse outcome pathway from drug-mediated bile salt export pump inhibition to cholestatic liver injury","volume":"136","author":"Vinken","year":"2013","journal-title":"Toxicol. Sci."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B45","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/jac\/29.6.649","article-title":"The in-vitro activity of two new quinolones: Rufloxacin and MF 961","volume":"29","author":"Wise","year":"1992","journal-title":"J. Antimicrob. Chemother."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B46","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.taap.2015.01.015","article-title":"Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis","volume":"283","author":"Woolbright","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"key\n\t\t\t\t2019032711394927700_kfz009-B47","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1517\/14728222.2016.1103735","article-title":"Therapeutic targets for cholestatic liver injury","volume":"20","author":"Woolbright","year":"2016","journal-title":"Expert Opin. Ther. Targets"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/168\/2\/474\/28230128\/kfz009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T10:50:50Z","timestamp":1573642250000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/168\/2\/474\/5285936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,10]]},"references-count":47,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,1,10]]},"published-print":{"date-parts":[[2019,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfz009","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734840981.793559402","asserted-by":"object"}]},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,4]]},"published":{"date-parts":[[2019,1,10]]}}}