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The present study was designed to evaluate whether HepaRG cells can also be useful for studying drug\u2010mediated inhibition of canalicular and\/or sinusoidal hepatic efflux of bile acids, which constitutes a major mechanism of drug\u2010induced liver toxicity. For this purpose, HepaRG cells, initially loaded with the bile acid taurocholate (TC), were reincubated in TC\u2010free transport assay medium, in the presence or absence of calcium or drugs, before analysis of TC retention. This method allowed us to objectivize and quantitatively measure biliary and sinusoidal efflux of TC from HepaRG cells, through distinguishing cellular and canalicular compartments. In particular, time\u2010course analysis of the TC\u2010free reincubation period of HepaRG cells, that is, the efflux period, indicated that a 20\u00a0min\u2010efflux period allowed reaching biliary and sinusoidal excretion indexes for TC around 80% and 60%, respectively. Addition of the prototypical cholestatic drugs bosentan, cyclosporin A, glibenclamide, or troglitazone during the TC\u2010free efflux phase period was demonstrated to markedly inhibit canalicular and sinusoidal secretion of TC, whereas, by contrast, incubation with the noncholestatic compounds salicylic acid or flumazenil was without effect. Such data therefore support the use of human HepaRG cells for in vitro predicting drug\u2010induced liver toxicity (DILI) due to the inhibition of hepatic bile acid secretion, using a biphasic TC loading\/efflux assay.<\/jats:p>","DOI":"10.1002\/bdd.2333","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T03:54:35Z","timestamp":1664942075000},"page":"265-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Inhibition of canalicular and sinusoidal taurocholate efflux by cholestatic drugs in human hepatoma HepaRG cells"],"prefix":"10.1002","volume":"43","author":[{"given":"Marc","family":"Le V\u00e9e","sequence":"first","affiliation":[{"name":"Univ Rennes INSERM EHESP IRSET (Institut de recherche en sant\u00e9, environnement et travail)\u2014UMR_S 1085  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Moreau","sequence":"additional","affiliation":[{"name":"Centre de Pharmacocin\u00e9tique Technologie Servier Orl\u00e9ans France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Jouan","sequence":"additional","affiliation":[{"name":"Univ Rennes INSERM EHESP IRSET (Institut de recherche en sant\u00e9, environnement et travail)\u2014UMR_S 1085  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Denizot","sequence":"additional","affiliation":[{"name":"Centre de Pharmacocin\u00e9tique Technologie Servier Orl\u00e9ans France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Parmentier","sequence":"additional","affiliation":[{"name":"Centre de Pharmacocin\u00e9tique Technologie Servier Orl\u00e9ans France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-4255","authenticated-orcid":false,"given":"Olivier","family":"Fardel","sequence":"additional","affiliation":[{"name":"Univ Rennes, CHU Rennes, INSERM, EHESP, IRSET (Institut de recherche en sant\u00e9, environnement et travail)\u2014UMR_S 1085  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2012.685159"},{"issue":"10","key":"e_1_2_8_3_1","first-page":"1277","article-title":"P\u2010glycoprotein\u2010mediated in vitro biliary excretion in sandwich\u2010cultured rat hepatocytes","volume":"29","author":"Annaert P. 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