{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:49:24Z","timestamp":1793674164349,"version":"4.5.1"},"reference-count":128,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["MCIN\/AEI\/10.13039\/501100011033 by PID2022-136433OB \u2013C22"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033 by PID2022-136433OB \u2013C22"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["CNS2022-135425"],"award-info":[{"award-number":["CNS2022-135425"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023561","name":"Ministerio de Universidades","doi-asserted-by":"publisher","award":["FPU19\/02240"],"award-info":[{"award-number":["FPU19\/02240"]}],"id":[{"id":"10.13039\/501100023561","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/00223"],"award-info":[{"award-number":["PI21\/00223"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universitat de Valencia"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Drug-induced cholestasis is one of the major mechanisms implicated in drug-induced hepatotoxicity that poses a serious problem in terms of patient morbidity and mortality, healthcare system expenses and efficacy of newly developed drugs. Impaired bile acid homeostasis due to transporter alterations, hepatocellular injury or canalicular abnormalities is the most characteristic feature of cholestasis. Given the complexity of cholestasis and the different underlying mechanisms, new models and technologies that span a variety of biological processes are needed to accurately predict drugs\u2019 cholestatic potential. This review outlines the main triggering mechanisms of drug-induced cholestasis and summarizes the currently available in vitro systems and techniques that attempt to forecast and provide mechanistic details of cholestasis caused by drugs.<\/jats:p>","DOI":"10.1007\/s00204-025-04016-0","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T22:54:46Z","timestamp":1741647286000},"page":"2243-2260","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury"],"prefix":"10.1007","volume":"99","author":[{"given":"Enrique","family":"Timor-L\u00f3pez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-0874","authenticated-orcid":false,"given":"Laia","family":"Tolosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2532-790X","authenticated-orcid":false,"given":"M. Teresa","family":"Donato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"issue":"6","key":"4016_CR1","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/clpt.2011.58","volume":"89","author":"GP Aithal","year":"2011","unstructured":"Aithal GP, Watkins PB, Andrade RJ et al (2011) Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther 89(6):806\u2013815. https:\/\/doi.org\/10.1038\/clpt.2011.58","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"4016_CR2","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.ajpath.2010.11.026","volume":"178","author":"K Allen","year":"2011","unstructured":"Allen K, Jaeschke H, Copple BL (2011) Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. Am J Pathol 178(1):175\u2013186. https:\/\/doi.org\/10.1016\/j.ajpath.2010.11.026","journal-title":"Am J Pathol"},{"issue":"10","key":"4016_CR3","first-page":"1277","volume":"29","author":"PP Annaert","year":"2001","unstructured":"Annaert PP, Turncliff RZ, Booth CL, Thakker DR, Brouwer KL (2001) P-glycoprotein-mediated in vitro biliary excretion in sandwich-cultured rat hepatocytes. Drug Metab Dispos 29(10):1277\u20131283","journal-title":"Drug Metab Dispos"},{"issue":"2","key":"4016_CR4","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1124\/dmd.109.028407","volume":"38","author":"JH Ansede","year":"2010","unstructured":"Ansede JH, Smith WR, Perry CH (2010) An in vitro assay to assess transporter-based cholestatic hepatotoxicity using sandwich-cultured rat hepatocytes. Drug Metab Dispos 38(2):276\u2013280. https:\/\/doi.org\/10.1124\/dmd.109.028407","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"4016_CR5","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1002\/hep.26160","volume":"57","author":"S Antherieu","year":"2013","unstructured":"Antherieu S, Bachour-El Azzi P, Dumont J et al (2013) Oxidative stress plays a major role in chlorpromazine-induced cholestasis in human HepaRG cells. Hepatology 57(4):1518\u20131529. https:\/\/doi.org\/10.1002\/hep.26160","journal-title":"Hepatology"},{"issue":"1","key":"4016_CR6","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1093\/toxsci\/kfv041","volume":"145","author":"P Bachour-El Azzi","year":"2015","unstructured":"Bachour-El Azzi P, Sharanek A, Burban A et al (2015) Comparative localization and functional activity of the main hepatobiliary transporters in HepaRG cells and primary human hepatocytes. Toxicol Sci 145(1):157\u2013168. https:\/\/doi.org\/10.1093\/toxsci\/kfv041","journal-title":"Toxicol Sci"},{"issue":"2","key":"4016_CR7","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3109\/00498254.2014.955831","volume":"45","author":"L Badolo","year":"2015","unstructured":"Badolo L, Jensen B, Sall C, Norinder U, Kallunki P, Montanari D (2015) Evaluation of 309 molecules as inducers of CYP3A4, CYP2B6, CYP1A2, OATP1B1, OCT1, MDR1, MRP2, MRP3 and BCRP in cryopreserved human hepatocytes in sandwich culture. Xenobiotica 45(2):177\u2013187. https:\/\/doi.org\/10.3109\/00498254.2014.955831","journal-title":"Xenobiotica"},{"issue":"8","key":"4016_CR8","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.2741\/3416","volume":"14","author":"N Ballatori","year":"2009","unstructured":"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 (Landmark Ed) 14(8):2829\u20132844. https:\/\/doi.org\/10.2741\/3416","journal-title":"Front Biosci (Landmark Ed)"},{"issue":"1","key":"4016_CR9","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1093\/toxsci\/kfv159","volume":"148","author":"JA Barber","year":"2015","unstructured":"Barber JA, Stahl SH, Summers C et al (2015) Quantification of drug-induced inhibition of canalicular Cholyl-l-Lysyl-fluorescein excretion from hepatocytes by high content cell imaging. Toxicol Sci 148(1):48\u201359. https:\/\/doi.org\/10.1093\/toxsci\/kfv159","journal-title":"Toxicol Sci"},{"issue":"9","key":"4016_CR10","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1124\/dmd.105.009118","volume":"34","author":"YA Bi","year":"2006","unstructured":"Bi YA, Kazolias D, Duignan DB (2006) Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport. Drug Metab Dispos 34(9):1658\u20131665. https:\/\/doi.org\/10.1124\/dmd.105.009118","journal-title":"Drug Metab Dispos"},{"issue":"3","key":"4016_CR11","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1002\/cphy.c120027","volume":"3","author":"JL Boyer","year":"2013","unstructured":"Boyer JL (2013) Bile formation and secretion. Compr Physiol 3(3):1035\u20131078. https:\/\/doi.org\/10.1002\/cphy.c120027","journal-title":"Compr Physiol"},{"key":"4016_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109728","volume":"351","author":"T Brecklinghaus","year":"2022","unstructured":"Brecklinghaus T, Albrecht W, Kappenberg F et al (2022) The hepatocyte export carrier inhibition assay improves the separation of hepatotoxic from non-hepatotoxic compounds. Chem Biol Interact 351:109728. https:\/\/doi.org\/10.1016\/j.cbi.2021.109728","journal-title":"Chem Biol Interact"},{"issue":"2","key":"4016_CR13","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1093\/toxsci\/kfz009","volume":"168","author":"A Burban","year":"2019","unstructured":"Burban A, Sharanek A, Humbert L et al (2019) Predictive value of cellular accumulation of hydrophobic bile acids as a marker of cholestatic drug potential. Toxicol Sci 168(2):474\u2013485. https:\/\/doi.org\/10.1093\/toxsci\/kfz009","journal-title":"Toxicol Sci"},{"issue":"2","key":"4016_CR14","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/toxsci\/kfx284","volume":"162","author":"R Chan","year":"2018","unstructured":"Chan R, Benet LZ (2018) Measures of bsep inhibition in vitro are not useful predictors of DILI. Toxicol Sci 162(2):499\u2013508. https:\/\/doi.org\/10.1093\/toxsci\/kfx284","journal-title":"Toxicol Sci"},{"issue":"2","key":"4016_CR15","doi-asserted-by":"publisher","first-page":"2866","DOI":"10.1080\/21655979.2021.2024970","volume":"13","author":"J Chen","year":"2022","unstructured":"Chen J, Wu H, Tang X, Chen L (2022) 4-Phenylbutyrate protects against rifampin-induced liver injury via regulating MRP2 ubiquitination through inhibiting endoplasmic reticulum stress. Bioengineered 13(2):2866\u20132877. https:\/\/doi.org\/10.1080\/21655979.2021.2024970","journal-title":"Bioengineered"},{"key":"4016_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2019.114666","volume":"379","author":"M Cuykx","year":"2019","unstructured":"Cuykx M, Beirnaert C, Rodrigues RM, Laukens K, Vanhaecke T, Covaci A (2019) Untargeted liquid chromatography-mass spectrometry metabolomics to assess drug-induced cholestatic features in HepaRG(R) cells. Toxicol Appl Pharmacol 379:114666. https:\/\/doi.org\/10.1016\/j.taap.2019.114666","journal-title":"Toxicol Appl Pharmacol"},{"key":"4016_CR17","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.toxlet.2022.06.004","volume":"365","author":"VMP de Bruijn","year":"2022","unstructured":"de Bruijn VMP, Wang Z, Bakker W, Zheng W, Spee B, Bouwmeester H (2022) Hepatic bile acid synthesis and secretion: comparison of in vitro methods. Toxicol Lett 365:46\u201360. https:\/\/doi.org\/10.1016\/j.toxlet.2022.06.004","journal-title":"Toxicol Lett"},{"issue":"4","key":"4016_CR18","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1517\/17425255.2014.884069","volume":"10","author":"M De Lima Toccafondo Vieira","year":"2014","unstructured":"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(4):581\u2013597. https:\/\/doi.org\/10.1517\/17425255.2014.884069","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"11","key":"4016_CR19","doi-asserted-by":"publisher","first-page":"5018","DOI":"10.1002\/jps.22694","volume":"100","author":"T De Bruyn","year":"2011","unstructured":"De Bruyn T, Fattah S, Stieger B, Augustijns P, Annaert P (2011) Sodium fluorescein is a probe substrate for hepatic drug transport mediated by OATP1B1 and OATP1B3. J Pharm Sci 100(11):5018\u20135030. https:\/\/doi.org\/10.1002\/jps.22694","journal-title":"J Pharm Sci"},{"issue":"3","key":"4016_CR20","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1152\/physrev.00035.2005","volume":"86","author":"RG Deeley","year":"2006","unstructured":"Deeley RG, Westlake C, Cole SP (2006) Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Physiol Rev 86(3):849\u2013899. https:\/\/doi.org\/10.1152\/physrev.00035.2005","journal-title":"Physiol Rev"},{"issue":"6","key":"4016_CR21","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1080\/10408444.2019.1635081","volume":"49","author":"N Deferm","year":"2019","unstructured":"Deferm N, De Vocht T, Qi B et al (2019a) Current insights in the complexities underlying drug-induced cholestasis. Crit Rev Toxicol 49(6):520\u2013548. https:\/\/doi.org\/10.1080\/10408444.2019.1635081","journal-title":"Crit Rev Toxicol"},{"key":"4016_CR22","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/978-1-4939-9420-5_22","volume":"1981","author":"N Deferm","year":"2019","unstructured":"Deferm N, Richert L, Van Brantegem P et al (2019b) Detection of drug-induced cholestasis potential in sandwich-cultured human hepatocytes. Methods Mol Biol 1981:335\u2013350. https:\/\/doi.org\/10.1007\/978-1-4939-9420-5_22","journal-title":"Methods Mol Biol"},{"issue":"4","key":"4016_CR23","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.jhep.2003.12.001","volume":"40","author":"GU Denk","year":"2004","unstructured":"Denk GU, Soroka CJ, Takeyama Y, Chen WS, 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(4):585\u2013591. https:\/\/doi.org\/10.1016\/j.jhep.2003.12.001","journal-title":"J Hepatol"},{"key":"4016_CR24","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.toxlet.2016.10.008","volume":"263","author":"MT Donato","year":"2016","unstructured":"Donato MT, Lopez-Riera M, Castell JV, Gomez-Lechon 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\u201367. https:\/\/doi.org\/10.1016\/j.toxlet.2016.10.008","journal-title":"Toxicol Lett"},{"issue":"6","key":"4016_CR25","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.jhep.2019.02.014","volume":"70","author":"European Association for the Study of the Liver. Electronic address eee, Clinical Practice Guideline Panel C, Panel m, representative EGB","year":"2019","unstructured":"European Association for the Study of the Liver. Electronic address eee, Clinical Practice Guideline Panel C, Panel m, representative EGB (2019) EASL clinical practice guidelines: drug-induced liver injury. J Hepatol 70(6):1222\u20131261. https:\/\/doi.org\/10.1016\/j.jhep.2019.02.014","journal-title":"J Hepatol"},{"issue":"4","key":"4016_CR26","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.jhep.2021.06.021","volume":"75","author":"JC Fernandez-Checa","year":"2021","unstructured":"Fernandez-Checa JC, Bagnaninchi P, Ye H et al (2021) Advanced preclinical models for evaluation of drug-induced liver injury\u2014consensus statement by the European Drug-Induced Liver Injury Network [PRO-EURO-DILI-NET]. J Hepatol 75(4):935\u2013959. https:\/\/doi.org\/10.1016\/j.jhep.2021.06.021","journal-title":"J Hepatol"},{"issue":"4","key":"4016_CR27","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1152\/ajpgi.00468.2002","volume":"284","author":"M Fuchs","year":"2003","unstructured":"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(4):551\u2013557. https:\/\/doi.org\/10.1152\/ajpgi.00468.2002","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"3","key":"4016_CR28","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1124\/dmd.113.054189","volume":"42","author":"B Garzel","year":"2014","unstructured":"Garzel B, Yang H, Zhang L, Huang SM, Polli JE, Wang H (2014) The role of bile salt export pump gene repression in drug-induced cholestatic liver toxicity. Drug Metab Dispos 42(3):318\u2013322. https:\/\/doi.org\/10.1124\/dmd.113.054189","journal-title":"Drug Metab Dispos"},{"issue":"16","key":"4016_CR29","doi-asserted-by":"publisher","first-page":"10046","DOI":"10.1074\/jbc.273.16.10046","volume":"273","author":"T Gerloff","year":"1998","unstructured":"Gerloff T, Stieger B, Hagenbuch B et al (1998) The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 273(16):10046\u201310050. https:\/\/doi.org\/10.1074\/jbc.273.16.10046","journal-title":"J Biol Chem"},{"issue":"2","key":"4016_CR30","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.jhep.2023.10.035","volume":"80","author":"A Ghallab","year":"2024","unstructured":"Ghallab A, Gonzalez D, Strangberg E et al (2024) Inhibition of the renal apical sodium dependent bile acid transporter prevents cholemic nephropathy in mice with obstructive cholestasis. J Hepatol 80(2):268\u2013281. https:\/\/doi.org\/10.1016\/j.jhep.2023.10.035","journal-title":"J Hepatol"},{"issue":"5","key":"4016_CR31","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1007\/s00204-019-02437-2","volume":"93","author":"E Gijbels","year":"2019","unstructured":"Gijbels E, Vilas-Boas V, Deferm N et al (2019) Mechanisms and in vitro models of drug-induced cholestasis. Arch Toxicol 93(5):1169\u20131186. https:\/\/doi.org\/10.1007\/s00204-019-02437-2","journal-title":"Arch Toxicol"},{"key":"4016_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.dib.2020.106156","volume":"32","author":"E Gijbels","year":"2020","unstructured":"Gijbels E, Devisscher L, Vinken M (2020a) Dataset on transcriptomic profiling of cholestatic liver injury in an in vitro and in vivo animal model. Data Brief 32:106156. https:\/\/doi.org\/10.1016\/j.dib.2020.106156","journal-title":"Data Brief"},{"issue":"4","key":"4016_CR33","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1007\/s00204-020-02691-9","volume":"94","author":"E Gijbels","year":"2020","unstructured":"Gijbels E, Vilas-Boas V, Annaert P, Vanhaecke T, Devisscher L, Vinken M (2020b) Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol 94(4):1151\u20131172. https:\/\/doi.org\/10.1007\/s00204-020-02691-9","journal-title":"Arch Toxicol"},{"key":"4016_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112165","volume":"152","author":"E Gijbels","year":"2021","unstructured":"Gijbels E, Devisscher L, Vinken M (2021) Testing in vitro tools for the prediction of cholestatic liver injury induced by non-pharmaceutical chemicals. Food Chem Toxicol 152:112165. https:\/\/doi.org\/10.1016\/j.fct.2021.112165","journal-title":"Food Chem Toxicol"},{"issue":"3","key":"4016_CR35","doi-asserted-by":"publisher","first-page":"G499","DOI":"10.1152\/ajpgi.00318.2003","volume":"286","author":"JS Gujral","year":"2004","unstructured":"Gujral JS, Liu J, Farhood A, Hinson JA, Jaeschke H (2004) Functional importance of ICAM-1 in the mechanism of neutrophil-induced liver injury in bile duct-ligated mice. Am J Physiol Gastrointest Liver Physiol 286(3):G499-507. https:\/\/doi.org\/10.1152\/ajpgi.00318.2003","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"1","key":"4016_CR36","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/toxsci\/kft021","volume":"133","author":"P Gunness","year":"2013","unstructured":"Gunness P, Mueller D, Shevchenko V, Heinzle E, Ingelman-Sundberg M, Noor F (2013) 3D organotypic cultures of human HepaRG cells: a tool for in vitro toxicity studies. Toxicol Sci 133(1):67\u201378. https:\/\/doi.org\/10.1093\/toxsci\/kft021","journal-title":"Toxicol Sci"},{"issue":"5","key":"4016_CR37","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1007\/s00424-003-1130-z","volume":"447","author":"B Hagenbuch","year":"2004","unstructured":"Hagenbuch B, Dawson P (2004) The sodium bile salt cotransport family SLC10. Pflugers Arch 447(5):566\u2013570. https:\/\/doi.org\/10.1007\/s00424-003-1130-z","journal-title":"Pflugers Arch"},{"issue":"1","key":"4016_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0005-2736(02)00633-8","volume":"1609","author":"B Hagenbuch","year":"2003","unstructured":"Hagenbuch B, Meier PJ (2003) The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta 1609(1):1\u201318. https:\/\/doi.org\/10.1016\/s0005-2736(02)00633-8","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"4016_CR39","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.stemcr.2020.12.008","volume":"16","author":"H Hayashi","year":"2021","unstructured":"Hayashi H, Osaka S, Sakabe K et al (2021) Modeling human bile acid transport and synthesis in stem cell-derived hepatocytes with a patient-specific mutation. Stem Cell Reports 16(2):309\u2013323. https:\/\/doi.org\/10.1016\/j.stemcr.2020.12.008","journal-title":"Stem Cell Reports"},{"key":"4016_CR40","doi-asserted-by":"publisher","first-page":"35434","DOI":"10.1038\/srep35434","volume":"6","author":"DF Hendriks","year":"2016","unstructured":"Hendriks DF, 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. https:\/\/doi.org\/10.1038\/srep35434","journal-title":"Sci Rep"},{"issue":"7","key":"4016_CR41","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1023\/b:pham.0000033018.97745.0d","volume":"21","author":"KA Hoffmaster","year":"2004","unstructured":"Hoffmaster KA, Turncliff RZ, LeCluyse EL, Kim RB, Meier PJ, Brouwer KL (2004) P-glycoprotein expression, localization, and function in sandwich-cultured primary rat and human hepatocytes: relevance to the hepatobiliary disposition of a model opioid peptide. Pharm Res 21(7):1294\u20131302. https:\/\/doi.org\/10.1023\/b:pham.0000033018.97745.0d","journal-title":"Pharm Res"},{"issue":"1","key":"4016_CR42","doi-asserted-by":"publisher","first-page":"16","DOI":"10.2133\/dmpk.18.16","volume":"18","author":"M Horikawa","year":"2003","unstructured":"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\u201322. https:\/\/doi.org\/10.2133\/dmpk.18.16","journal-title":"Drug Metab Pharmacokinet"},{"key":"4016_CR43","doi-asserted-by":"publisher","first-page":"1022809","DOI":"10.3389\/fphar.2022.1022809","volume":"13","author":"W Hou","year":"2022","unstructured":"Hou W, Nsengimana B, Yan C, Nashan B, Han S (2022) Involvement of endoplasmic reticulum stress in rifampicin-induced liver injury. Front Pharmacol 13:1022809. https:\/\/doi.org\/10.3389\/fphar.2022.1022809","journal-title":"Front Pharmacol"},{"issue":"6","key":"4016_CR44","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1152\/ajpgi.00568.2005","volume":"290","author":"H Jaeschke","year":"2006","unstructured":"Jaeschke H (2006) Mechanisms of liver injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions. Am J Physiol Gastrointest Liver Physiol 290(6):1083\u20131088. https:\/\/doi.org\/10.1152\/ajpgi.00568.2005","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"2","key":"4016_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.22037\/ijpr.2020.113362.14254","volume":"20","author":"F Jazaeri","year":"2021","unstructured":"Jazaeri F, Sheibani M, Nezamoleslami S, Moezi L, Dehpour AR (2021) Current models for predicting drug-induced cholestasis: the role of hepatobiliary transport system. Iran J Pharm Res 20(2):1\u201321. https:\/\/doi.org\/10.22037\/ijpr.2020.113362.14254","journal-title":"Iran J Pharm Res"},{"key":"4016_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.04.018","volume":"154","author":"A Jetter","year":"2020","unstructured":"Jetter A, Kullak-Ublick GA (2020) Drugs and hepatic transporters: a review. Pharmacol Res 154:104234. https:\/\/doi.org\/10.1016\/j.phrs.2019.04.018","journal-title":"Pharmacol Res"},{"issue":"11","key":"4016_CR47","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1007\/s00204-023-03583-4","volume":"97","author":"J Jiang","year":"2023","unstructured":"Jiang J, van Ertvelde J, Ertaylan G et al (2023) Unraveling the mechanisms underlying drug-induced cholestatic liver injury: identifying key genes using machine learning techniques on human in vitro data sets. Arch Toxicol 97(11):2969\u20132981. https:\/\/doi.org\/10.1007\/s00204-023-03583-4","journal-title":"Arch Toxicol"},{"issue":"7","key":"4016_CR48","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1124\/dmd.107.020016","volume":"36","author":"KP Kanebratt","year":"2008","unstructured":"Kanebratt KP, Andersson TB (2008) Evaluation of HepaRG cells as an in vitro model for human drug metabolism studies. Drug Metab Dispos 36(7):1444\u20131452. https:\/\/doi.org\/10.1124\/dmd.107.020016","journal-title":"Drug Metab Dispos"},{"issue":"2","key":"4016_CR49","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/toxsci\/kfi020","volume":"83","author":"DC Kemp","year":"2005","unstructured":"Kemp DC, Zamek-Gliszczynski MJ, Brouwer KL (2005) Xenobiotics inhibit hepatic uptake and biliary excretion of taurocholate in rat hepatocytes. Toxicol Sci 83(2):207\u2013214. https:\/\/doi.org\/10.1093\/toxsci\/kfi020","journal-title":"Toxicol Sci"},{"issue":"5","key":"4016_CR50","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1002\/cpt.1222","volume":"104","author":"JG Kenna","year":"2018","unstructured":"Kenna JG, Taskar KS, Battista C et al (2018) Can bile salt export pump inhibition testing in drug discovery and development reduce liver injury risk? An International transporter consortium perspective. Clin Pharmacol Ther 104(5):916\u2013932. https:\/\/doi.org\/10.1002\/cpt.1222","journal-title":"Clin Pharmacol Ther"},{"key":"4016_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2024.106598","volume":"172","author":"P Kettel","year":"2024","unstructured":"Kettel P, Karagoz GE (2024) Endoplasmic reticulum: monitoring and maintaining protein and membrane homeostasis in the endoplasmic reticulum by the unfolded protein response. Int J Biochem Cell Biol 172:106598. https:\/\/doi.org\/10.1016\/j.biocel.2024.106598","journal-title":"Int J Biochem Cell Biol"},{"issue":"10","key":"4016_CR52","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1124\/dmd.108.021410","volume":"36","author":"S Kitamura","year":"2008","unstructured":"Kitamura S, Maeda K, Wang Y, Sugiyama Y (2008) Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos 36(10):2014\u20132023. https:\/\/doi.org\/10.1124\/dmd.108.021410","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"4016_CR53","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1124\/dmd.113.054304","volume":"42","author":"K Kock","year":"2014","unstructured":"Kock K, Ferslew BC, Netterberg I et al (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 42(4):665\u2013674. https:\/\/doi.org\/10.1124\/dmd.113.054304","journal-title":"Drug Metab Dispos"},{"issue":"1","key":"4016_CR54","doi-asserted-by":"publisher","first-page":"47","DOI":"10.2131\/jts.48.47","volume":"48","author":"T Koga","year":"2023","unstructured":"Koga T, Takeuchi K, Umehara K (2023) Establishment of an in vitro cholestasis risk assessment system using two-dimensional cultured HepaRG cells and 12 bile acids. J Toxicol Sci 48(1):47\u201356. https:\/\/doi.org\/10.2131\/jts.48.47","journal-title":"J Toxicol Sci"},{"issue":"1","key":"4016_CR55","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1093\/toxsci\/kfg217","volume":"76","author":"VE Kostrubsky","year":"2003","unstructured":"Kostrubsky VE, Strom SC, Hanson J et al (2003) Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats. Toxicol Sci 76(1):220\u2013228. https:\/\/doi.org\/10.1093\/toxsci\/kfg217","journal-title":"Toxicol Sci"},{"issue":"1","key":"4016_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/toxsci\/kfab069","volume":"183","author":"T Kralj","year":"2021","unstructured":"Kralj T, Brouwer KLR, Creek DJ (2021) Analytical and omics-based advances in the study of drug-induced liver injury. Toxicol Sci 183(1):1\u201313. https:\/\/doi.org\/10.1093\/toxsci\/kfab069","journal-title":"Toxicol Sci"},{"key":"4016_CR57","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.bcp.2018.06.026","volume":"155","author":"AJ Kvist","year":"2018","unstructured":"Kvist AJ, Kanebratt KP, Walentinsson A et al (2018) Critical differences in drug metabolic properties of human hepatic cellular models, including primary human hepatocytes, stem cell derived hepatocytes, and hepatoma cell lines. Biochem Pharmacol 155:124\u2013140. https:\/\/doi.org\/10.1016\/j.bcp.2018.06.026","journal-title":"Biochem Pharmacol"},{"issue":"6","key":"4016_CR58","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1016\/j.tiv.2013.07.003","volume":"27","author":"M Le Vee","year":"2013","unstructured":"Le Vee M, Noel G, Jouan E, Stieger B, Fardel O (2013) Polarized expression of drug transporters in differentiated human hepatoma HepaRG cells. Toxicol in Vitro 27(6):1979\u20131986. https:\/\/doi.org\/10.1016\/j.tiv.2013.07.003","journal-title":"Toxicol in Vitro"},{"issue":"6","key":"4016_CR59","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1002\/bdd.2333","volume":"43","author":"M Le Vee","year":"2022","unstructured":"Le Vee M, Moreau A, Jouan E, Denizot C, Parmentier Y, Fardel O (2022) Inhibition of canalicular and sinusoidal taurocholate efflux by cholestatic drugs in human hepatoma HepaRG cells. Biopharm Drug Dispos 43(6):265\u2013271. https:\/\/doi.org\/10.1002\/bdd.2333","journal-title":"Biopharm Drug Dispos"},{"issue":"2","key":"4016_CR60","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/s0887-2333(99)00096-x","volume":"14","author":"EL LeCluyse","year":"2000","unstructured":"LeCluyse EL, Fix JA, Audus KL, Hochman JH (2000) Regeneration and maintenance of bile canalicular networks in collagen-sandwiched hepatocytes. Toxicol in Vitro 14(2):117\u2013132. https:\/\/doi.org\/10.1016\/s0887-2333(99)00096-x","journal-title":"Toxicol in Vitro"},{"key":"4016_CR61","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.freeradbiomed.2013.07.038","volume":"65","author":"KK Lee","year":"2013","unstructured":"Lee KK, Fujimoto K, Zhang C et al (2013) Isoniazid-induced cell death is precipitated by underlying mitochondrial complex I dysfunction in mouse hepatocytes. Free Radic Biol Med 65:584\u2013594. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2013.07.038","journal-title":"Free Radic Biol Med"},{"issue":"9\u201310","key":"4016_CR62","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s10495-020-01627-z","volume":"25","author":"YS Lee","year":"2020","unstructured":"Lee YS, Kalimuthu K, Park YS et al (2020) BAX-dependent mitochondrial pathway mediates the crosstalk between ferroptosis and apoptosis. Apoptosis 25(9\u201310):625\u2013631. https:\/\/doi.org\/10.1007\/s10495-020-01627-z","journal-title":"Apoptosis"},{"issue":"3","key":"4016_CR63","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1124\/jpet.106.119073","volume":"321","author":"EM Leslie","year":"2007","unstructured":"Leslie EM, Watkins PB, Kim RB, Brouwer KL (2007) Differential inhibition of rat and human Na+-dependent taurocholate cotransporting polypeptide (NTCP\/SLC10A1)by bosentan: a mechanism for species differences in hepatotoxicity. J Pharmacol Exp Ther 321(3):1170\u20131178. https:\/\/doi.org\/10.1124\/jpet.106.119073","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"4016_CR64","doi-asserted-by":"publisher","first-page":"40","DOI":"10.14218\/JCTH.2018.00052","volume":"7","author":"F Li","year":"2019","unstructured":"Li F, Zhou J, Li Y, Sun K, Chen J (2019) Mitochondrial damage and Drp1 overexpression in rifampicin- and isoniazid-induced liver injury cell model. J Clin Transl Hepatol 7(1):40\u201345. https:\/\/doi.org\/10.14218\/JCTH.2018.00052","journal-title":"J Clin Transl Hepatol"},{"issue":"4","key":"4016_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2022.100446","volume":"4","author":"CZ Li","year":"2022","unstructured":"Li CZ, Ogawa H, Ng SS et al (2022) Human iPSC-derived hepatocyte system models cholestasis with tight junction protein 2 deficiency. JHEP Rep 4(4):100446. https:\/\/doi.org\/10.1016\/j.jhepr.2022.100446","journal-title":"JHEP Rep"},{"issue":"1","key":"4016_CR66","doi-asserted-by":"publisher","first-page":"G12","DOI":"10.1152\/ajpgi.1999.277.1.G12","volume":"277","author":"X Liu","year":"1999","unstructured":"Liu X, LeCluyse EL, Brouwer KR et al (1999) Biliary excretion in primary rat hepatocytes cultured in a collagen-sandwich configuration. Am J Physiol 277(1):G12-21. https:\/\/doi.org\/10.1152\/ajpgi.1999.277.1.G12","journal-title":"Am J Physiol"},{"issue":"1","key":"4016_CR67","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/toxsci\/kfv117","volume":"147","author":"J Lu","year":"2015","unstructured":"Lu J, Einhorn S, Venkatarangan L et al (2015) Morphological and functional characterization and assessment of iPSC-derived hepatocytes for in vitro toxicity testing. Toxicol Sci 147(1):39\u201354. https:\/\/doi.org\/10.1093\/toxsci\/kfv117","journal-title":"Toxicol Sci"},{"issue":"6","key":"4016_CR68","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1021\/mp0700357","volume":"4","author":"TL Marion","year":"2007","unstructured":"Marion TL, Leslie EM, Brouwer KL (2007) Use of sandwich-cultured hepatocytes to evaluate impaired bile acid transport as a mechanism of drug-induced hepatotoxicity. Mol Pharm 4(6):911\u2013918. https:\/\/doi.org\/10.1021\/mp0700357","journal-title":"Mol Pharm"},{"issue":"1","key":"4016_CR69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.taap.2012.02.002","volume":"261","author":"TL Marion","year":"2012","unstructured":"Marion TL, Perry CH, St Claire RL, Brouwer KL (2012) Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes. Toxicol Appl Pharmacol 261(1):1\u20139. https:\/\/doi.org\/10.1016\/j.taap.2012.02.002","journal-title":"Toxicol Appl Pharmacol"},{"issue":"5","key":"4016_CR70","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1124\/mol.107.041459","volume":"73","author":"S Matsushima","year":"2008","unstructured":"Matsushima S, Maeda K, Hayashi H et al (2008) Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol 73(5):1474\u20131483. https:\/\/doi.org\/10.1124\/mol.107.041459","journal-title":"Mol Pharmacol"},{"key":"4016_CR71","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1146\/annurev.physiol.64.082201.100300","volume":"64","author":"PJ Meier","year":"2002","unstructured":"Meier PJ, Stieger B (2002) Bile salt transporters. Annu Rev Physiol 64:635\u2013661. https:\/\/doi.org\/10.1146\/annurev.physiol.64.082201.100300","journal-title":"Annu Rev Physiol"},{"key":"4016_CR72","doi-asserted-by":"publisher","DOI":"10.3390\/cells11030537","author":"A Messina","year":"2022","unstructured":"Messina A, Luce E, Benzoubir N et al (2022) Evidence of adult features and functions of hepatocytes differentiated from human induced pluripotent stem cells and self-organized as organoids. Cells. https:\/\/doi.org\/10.3390\/cells11030537","journal-title":"Cells"},{"issue":"1","key":"4016_CR73","doi-asserted-by":"publisher","first-page":"G159","DOI":"10.1152\/ajpgi.00360.2003","volume":"288","author":"S Mita","year":"2005","unstructured":"Mita S, Suzuki H, Akita H et al (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(1):G159\u2013G167. https:\/\/doi.org\/10.1152\/ajpgi.00360.2003","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"3","key":"4016_CR74","doi-asserted-by":"publisher","first-page":"G550","DOI":"10.1152\/ajpgi.00364.2005","volume":"290","author":"S Mita","year":"2006","unstructured":"Mita S, Suzuki H, Akita H et al (2006) Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep. Am J Physiol Gastrointest Liver Physiol 290(3):G550\u2013G556. https:\/\/doi.org\/10.1152\/ajpgi.00364.2005","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"2","key":"4016_CR75","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1093\/toxsci\/kfq269","volume":"118","author":"RE Morgan","year":"2010","unstructured":"Morgan RE, Trauner M, van Staden CJ et al (2010) Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci 118(2):485\u2013500. https:\/\/doi.org\/10.1093\/toxsci\/kfq269","journal-title":"Toxicol Sci"},{"issue":"1","key":"4016_CR76","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1093\/toxsci\/kft176","volume":"136","author":"RE Morgan","year":"2013","unstructured":"Morgan RE, van Staden CJ, Chen Y et al (2013) A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci 136(1):216\u2013241. https:\/\/doi.org\/10.1093\/toxsci\/kft176","journal-title":"Toxicol Sci"},{"issue":"14","key":"4016_CR77","doi-asserted-by":"publisher","first-page":"8151","DOI":"10.1111\/jcmm.15474","volume":"24","author":"W Mu","year":"2020","unstructured":"Mu W, Cheng X, Zhang X et al (2020) Hinokiflavone induces apoptosis via activating mitochondrial ROS\/JNK\/caspase pathway and inhibiting NF-kappaB activity in hepatocellular carcinoma. J Cell Mol Med 24(14):8151\u20138165. https:\/\/doi.org\/10.1111\/jcmm.15474","journal-title":"J Cell Mol Med"},{"issue":"1","key":"4016_CR78","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.tiv.2013.06.024","volume":"28","author":"D Mueller","year":"2014","unstructured":"Mueller D, Kramer L, Hoffmann E, Klein S, Noor F (2014) 3D organotypic HepaRG cultures as in vitro model for acute and repeated dose toxicity studies. Toxicol in Vitro 28(1):104\u2013112. https:\/\/doi.org\/10.1016\/j.tiv.2013.06.024","journal-title":"Toxicol in Vitro"},{"key":"4016_CR79","doi-asserted-by":"publisher","first-page":"38694","DOI":"10.1038\/srep38694","volume":"6","author":"X Ni","year":"2016","unstructured":"Ni X, Gao Y, Wu Z et al (2016) Functional human induced hepatocytes (hiHeps) with bile acid synthesis and transport capacities: a novel in vitro cholestatic model. Sci Rep 6:38694. https:\/\/doi.org\/10.1038\/srep38694","journal-title":"Sci Rep"},{"key":"4016_CR80","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.ejps.2018.01.007","volume":"115","author":"S Notenboom","year":"2018","unstructured":"Notenboom S, Weigand KM, Proost JH et al (2018) Development of a mechanistic biokinetic model for hepatic bile acid handling to predict possible cholestatic effects of drugs. Eur J Pharm Sci 115:175\u2013184. https:\/\/doi.org\/10.1016\/j.ejps.2018.01.007","journal-title":"Eur J Pharm Sci"},{"issue":"1","key":"4016_CR81","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.cbi.2004.09.003","volume":"150","author":"PJ O\u2019Brien","year":"2004","unstructured":"O\u2019Brien PJ, Chan K, Silber PM (2004) Human and animal hepatocytes in vitro with extrapolation in vivo. Chem Biol Interact 150(1):97\u2013114. https:\/\/doi.org\/10.1016\/j.cbi.2004.09.003","journal-title":"Chem Biol Interact"},{"issue":"3\u20134","key":"4016_CR82","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.bbrc.2011.11.032","volume":"416","author":"E Ogimura","year":"2011","unstructured":"Ogimura E, Sekine S, Horie T (2011) Bile salt export pump inhibitors are associated with bile acid-dependent drug-induced toxicity in sandwich-cultured hepatocytes. Biochem Biophys Res Commun 416(3\u20134):313\u2013317. https:\/\/doi.org\/10.1016\/j.bbrc.2011.11.032","journal-title":"Biochem Biophys Res Commun"},{"key":"4016_CR83","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.vascn.2015.03.002","volume":"73","author":"M Oorts","year":"2015","unstructured":"Oorts M, Richert L, Annaert P (2015) Drug-induced cholestasis detection in cryopreserved rat hepatocytes in sandwich culture. J Pharmacol Toxicol Methods 73:63\u201371. https:\/\/doi.org\/10.1016\/j.vascn.2015.03.002","journal-title":"J Pharmacol Toxicol Methods"},{"issue":"8","key":"4016_CR84","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1007\/s00204-017-1930-0","volume":"91","author":"C Parmentier","year":"2017","unstructured":"Parmentier C, Couttet P, Wolf A et al (2017) Evaluation of transcriptomic signature as a valuable tool to study drug-induced cholestasis in primary human hepatocytes. Arch Toxicol 91(8):2879\u20132893. https:\/\/doi.org\/10.1007\/s00204-017-1930-0","journal-title":"Arch Toxicol"},{"issue":"4","key":"4016_CR85","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/hep.21359","volume":"44","author":"C Pauli-Magnus","year":"2006","unstructured":"Pauli-Magnus C, Meier PJ (2006) Hepatobiliary transporters and drug-induced cholestasis. Hepatology 44(4):778\u2013787. https:\/\/doi.org\/10.1002\/hep.21359","journal-title":"Hepatology"},{"issue":"2","key":"4016_CR86","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1093\/toxsci\/kft197","volume":"136","author":"JM Pedersen","year":"2013","unstructured":"Pedersen JM, Matsson P, Bergstrom CA et al (2013) Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP\/ABCB11). Toxicol Sci 136(2):328\u2013343. https:\/\/doi.org\/10.1093\/toxsci\/kft197","journal-title":"Toxicol Sci"},{"key":"4016_CR87","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112664","volume":"158","author":"PD Petrov","year":"2021","unstructured":"Petrov PD, Soluyanova P, Sanchez-Campos S, Castell JV, Jover R (2021) Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol 158:112664. https:\/\/doi.org\/10.1016\/j.fct.2021.112664","journal-title":"Food Chem Toxicol"},{"issue":"8","key":"4016_CR88","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1248\/bpb.b18-00028","volume":"41","author":"X Qu","year":"2018","unstructured":"Qu X, Zhang Y, Zhang S et al (2018) Dysregulation of BSEP and MRP2 may play an important role in isoniazid-induced liver injury via the SIRT1\/FXR pathway in rats and HepG2 cells. Biol Pharm Bull 41(8):1211\u20131218. https:\/\/doi.org\/10.1248\/bpb.b18-00028","journal-title":"Biol Pharm Bull"},{"issue":"5","key":"4016_CR89","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1007\/s00204-014-1215-9","volume":"88","author":"SC Ramaiahgari","year":"2014","unstructured":"Ramaiahgari SC, den Braver MW, Herpers B et al (2014) A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies. Arch Toxicol 88(5):1083\u20131095. https:\/\/doi.org\/10.1007\/s00204-014-1215-9","journal-title":"Arch Toxicol"},{"issue":"1","key":"4016_CR90","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1093\/toxsci\/kfx194","volume":"160","author":"SC Ramaiahgari","year":"2017","unstructured":"Ramaiahgari SC, Waidyanatha S, Dixon D, DeVito MJ, Paules RS, Ferguson SS (2017) Three-dimensional (3D) HepaRG spheroid model with physiologically relevant xenobiotic metabolism competence and hepatocyte functionality for liver toxicity screening. Toxicol Sci 160(1):189\u2013190. https:\/\/doi.org\/10.1093\/toxsci\/kfx194","journal-title":"Toxicol Sci"},{"issue":"4","key":"4016_CR91","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1053\/j.gastro.2020.06.010","volume":"159","author":"MNB Ramli","year":"2020","unstructured":"Ramli MNB, Lim YS, Koe CT et al (2020) Human pluripotent stem cell-derived organoids as models of liver disease. Gastroenterology 159(4):1471-1486.e12. https:\/\/doi.org\/10.1053\/j.gastro.2020.06.010","journal-title":"Gastroenterology"},{"issue":"6","key":"4016_CR92","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1007\/s00204-018-2214-z","volume":"92","author":"RM Rodrigues","year":"2018","unstructured":"Rodrigues RM, Kollipara L, Chaudhari U et al (2018) Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol 92(6):1939\u20131952. https:\/\/doi.org\/10.1007\/s00204-018-2214-z","journal-title":"Arch Toxicol"},{"issue":"1","key":"4016_CR93","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s00204-021-03178-x","volume":"96","author":"S Rose","year":"2022","unstructured":"Rose S, Cuvellier M, Ezan F et al (2022) DMSO-free highly differentiated HepaRG spheroids for chronic toxicity, liver functions and genotoxicity studies. Arch Toxicol 96(1):243\u2013258. https:\/\/doi.org\/10.1007\/s00204-021-03178-x","journal-title":"Arch Toxicol"},{"issue":"8","key":"4016_CR94","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1021\/acs.chemrestox.6b00121","volume":"29","author":"M Sachar","year":"2016","unstructured":"Sachar M, Li F, Liu K, Wang P, Lu J, Ma X (2016) Chronic treatment with isoniazid causes protoporphyrin IX accumulation in mouse liver. Chem Res Toxicol 29(8):1293\u20131297. https:\/\/doi.org\/10.1021\/acs.chemrestox.6b00121","journal-title":"Chem Res Toxicol"},{"issue":"8","key":"4016_CR95","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1248\/bpb.b19-00249","volume":"42","author":"S Sanoh","year":"2019","unstructured":"Sanoh S, Tamura Y, Fujino C et al (2019) Changes in bile acid concentrations after administration of ketoconazole or rifampicin to chimeric mice with humanized liver. Biol Pharm Bull 42(8):1366\u20131375. https:\/\/doi.org\/10.1248\/bpb.b19-00249","journal-title":"Biol Pharm Bull"},{"issue":"3","key":"4016_CR96","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.clinre.2015.12.017","volume":"40","author":"HS Schadt","year":"2016","unstructured":"Schadt HS, Wolf A, Pognan F, Chibout SD, Merz M, Kullak-Ublick GA (2016) Bile acids in drug induced liver injury: Key players and surrogate markers. Clin Res Hepatol Gastroenterol 40(3):257\u2013266. https:\/\/doi.org\/10.1016\/j.clinre.2015.12.017","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"1","key":"4016_CR97","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1093\/toxsci\/kfu122","volume":"141","author":"A Sharanek","year":"2014","unstructured":"Sharanek A, Azzi PB, Al-Attrache H et al (2014) Different dose-dependent mechanisms are involved in early cyclosporine a-induced cholestatic effects in hepaRG cells. Toxicol Sci 141(1):244\u2013253. https:\/\/doi.org\/10.1093\/toxsci\/kfu122","journal-title":"Toxicol Sci"},{"issue":"2","key":"4016_CR98","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1093\/toxsci\/kfv155","volume":"147","author":"A Sharanek","year":"2015","unstructured":"Sharanek A, Burban A, Humbert L et al (2015) Cellular accumulation and toxic effects of bile acids in cyclosporine a-treated HepaRG hepatocytes. Toxicol Sci 147(2):573\u2013587. https:\/\/doi.org\/10.1093\/toxsci\/kfv155","journal-title":"Toxicol Sci"},{"key":"4016_CR99","doi-asserted-by":"publisher","first-page":"24709","DOI":"10.1038\/srep24709","volume":"6","author":"A Sharanek","year":"2016","unstructured":"Sharanek A, Burban A, Burbank M et al (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. https:\/\/doi.org\/10.1038\/srep24709","journal-title":"Sci Rep"},{"issue":"12","key":"4016_CR100","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1124\/dmd.117.077420","volume":"45","author":"A Sharanek","year":"2017","unstructured":"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(12):1292\u20131303. https:\/\/doi.org\/10.1124\/dmd.117.077420","journal-title":"Drug Metab Dispos"},{"issue":"3","key":"4016_CR101","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1053\/j.gastro.2020.10.002","volume":"160","author":"T Shinozawa","year":"2021","unstructured":"Shinozawa T, Kimura M, Cai Y et al (2021) High-fidelity drug-induced liver injury screen using human pluripotent stem cell-derived organoids. Gastroenterology 160(3):831-846.e10. https:\/\/doi.org\/10.1053\/j.gastro.2020.10.002","journal-title":"Gastroenterology"},{"issue":"10","key":"4016_CR102","doi-asserted-by":"publisher","first-page":"3403","DOI":"10.1007\/s00204-017-1960-7","volume":"91","author":"V Starokozhko","year":"2017","unstructured":"Starokozhko V, Greupink R, van de Broek P et al (2017) Rat precision-cut liver slices predict drug-induced cholestatic injury. Arch Toxicol 91(10):3403\u20133413. https:\/\/doi.org\/10.1007\/s00204-017-1960-7","journal-title":"Arch Toxicol"},{"issue":"4","key":"4016_CR103","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1517\/17425255.2011.557067","volume":"7","author":"B Stieger","year":"2011","unstructured":"Stieger B, Geier A (2011) Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis. Expert Opin Drug Metab Toxicol 7(4):411\u2013425. https:\/\/doi.org\/10.1517\/17425255.2011.557067","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"2","key":"4016_CR104","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/s0016-5085(00)70224-1","volume":"118","author":"B Stieger","year":"2000","unstructured":"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(2):422\u2013430. https:\/\/doi.org\/10.1016\/s0016-5085(00)70224-1","journal-title":"Gastroenterology"},{"issue":"4","key":"4016_CR105","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1016\/j.xphs.2016.01.013","volume":"105","author":"T Susukida","year":"2016","unstructured":"Susukida T, Sekine S, Nozaki M et al (2016) Establishment of a drug-induced, bile acid-dependent hepatotoxicity model using HepaRG cells. J Pharm Sci 105(4):1550\u20131560. https:\/\/doi.org\/10.1016\/j.xphs.2016.01.013","journal-title":"J Pharm Sci"},{"key":"4016_CR106","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1755-8794-6-39","volume":"6","author":"E Szalowska","year":"2013","unstructured":"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. https:\/\/doi.org\/10.1186\/1755-8794-6-39","journal-title":"BMC Med Genomics"},{"issue":"14","key":"4016_CR107","doi-asserted-by":"publisher","first-page":"13953","DOI":"10.1074\/jbc.M312170200","volume":"279","author":"E Szczesna-Skorupa","year":"2004","unstructured":"Szczesna-Skorupa E, Chen CD, Liu H, Kemper B (2004) Gene expression changes associated with the endoplasmic reticulum stress response induced by microsomal cytochrome p450 overproduction. J Biol Chem 279(14):13953\u201313961. https:\/\/doi.org\/10.1074\/jbc.M312170200","journal-title":"J Biol Chem"},{"issue":"2","key":"4016_CR108","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1152\/physrev.00027.2002","volume":"83","author":"M Trauner","year":"2003","unstructured":"Trauner M, Boyer JL (2003) Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 83(2):633\u2013671. https:\/\/doi.org\/10.1152\/physrev.00027.2002","journal-title":"Physiol Rev"},{"issue":"5","key":"4016_CR109","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.bcp.2013.06.029","volume":"86","author":"M Ulvestad","year":"2013","unstructured":"Ulvestad M, Nordell P, Asplund A et al (2013) Drug metabolizing enzyme and transporter protein profiles of hepatocytes derived from human embryonic and induced pluripotent stem cells. Biochem Pharmacol 86(5):691\u2013702. https:\/\/doi.org\/10.1016\/j.bcp.2013.06.029","journal-title":"Biochem Pharmacol"},{"issue":"3","key":"4016_CR110","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.tiv.2014.12.016","volume":"29","author":"WF Van den Hof","year":"2015","unstructured":"Van den Hof WF, Ruiz-Aracama A, Van Summeren A et al (2015) Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol in Vitro 29(3):489\u2013501. https:\/\/doi.org\/10.1016\/j.tiv.2014.12.016","journal-title":"Toxicol in Vitro"},{"key":"4016_CR111","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.tiv.2017.07.024","volume":"44","author":"W Van den Hof","year":"2017","unstructured":"Van den Hof W, Coonen MLJ, van Herwijnen M et al (2017) Validation of gene expression profiles from cholestatic hepatotoxicants in vitro against human in vivo cholestasis. Toxicol in Vitro 44:322\u2013329. https:\/\/doi.org\/10.1016\/j.tiv.2017.07.024","journal-title":"Toxicol in Vitro"},{"issue":"23","key":"4016_CR112","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/0471140856.tx2305s54","volume":"23","author":"CJ van Staden","year":"2012","unstructured":"van Staden CJ, Morgan RE, Ramachandran B, Chen Y, Lee PH, Hamadeh HK (2012) Membrane vesicle ABC transporter assays for drug safety assessment. Curr Protoc Toxicol Chapter 23(23):5. https:\/\/doi.org\/10.1002\/0471140856.tx2305s54","journal-title":"Curr Protoc Toxicol Chapter"},{"issue":"3","key":"4016_CR113","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1021\/acs.chemrestox.5b00491","volume":"29","author":"S Vatakuti","year":"2016","unstructured":"Vatakuti S, Pennings JL, Gore E, Olinga P, Groothuis GM (2016) Classification of cholestatic and necrotic hepatotoxicants using transcriptomics on human precision-cut liver slices. Chem Res Toxicol 29(3):342\u2013351. https:\/\/doi.org\/10.1021\/acs.chemrestox.5b00491","journal-title":"Chem Res Toxicol"},{"issue":"3","key":"4016_CR114","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1007\/s00204-016-1778-8","volume":"91","author":"S Vatakuti","year":"2017","unstructured":"Vatakuti S, Olinga P, Pennings JLA, Groothuis GMM (2017) Validation of precision-cut liver slices to study drug-induced cholestasis: a transcriptomics approach. Arch Toxicol 91(3):1401\u20131412. https:\/\/doi.org\/10.1007\/s00204-016-1778-8","journal-title":"Arch Toxicol"},{"key":"4016_CR115","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011005","author":"V Vilas-Boas","year":"2021","unstructured":"Vilas-Boas V, Gijbels E, Leroy K et al (2021) Primary human hepatocyte spheroids as tools to study the hepatotoxic potential of non-pharmaceutical chemicals. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms222011005","journal-title":"Int J Mol Sci"},{"key":"4016_CR116","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2022.153256","volume":"476","author":"Y Wen","year":"2022","unstructured":"Wen Y, Zhang G, Wu X (2022) The role of the farnesoid X receptor in quadruple anti-tuberculosis drug-induced liver injury. Toxicology 476:153256. https:\/\/doi.org\/10.1016\/j.tox.2022.153256","journal-title":"Toxicology"},{"issue":"12","key":"4016_CR117","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1021\/acs.chemrestox.6b00337","volume":"29","author":"JE Wolters","year":"2016","unstructured":"Wolters JE, van Herwijnen MH, Theunissen DH et al (2016) Integrative \u201c-omics\u201d analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol 29(12):2164\u20132174. https:\/\/doi.org\/10.1021\/acs.chemrestox.6b00337","journal-title":"Chem Res Toxicol"},{"issue":"3","key":"4016_CR118","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3727\/105221619X15614873062730","volume":"19","author":"BL Woolbright","year":"2019","unstructured":"Woolbright BL, Jaeschke H (2019) Inflammation and cell death during cholestasis: the evolving role of bile acids. Gene Expr 19(3):215\u2013228. https:\/\/doi.org\/10.3727\/105221619X15614873062730","journal-title":"Gene Expr"},{"issue":"2","key":"4016_CR119","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1111\/bcpt.12449","volume":"118","author":"BL Woolbright","year":"2016","unstructured":"Woolbright BL, McGill MR, Yan H, Jaeschke H (2016) Bile acid-induced toxicity in HepaRG cells recapitulates the response in primary human hepatocytes. Basic Clin Pharmacol Toxicol 118(2):160\u2013167. https:\/\/doi.org\/10.1111\/bcpt.12449","journal-title":"Basic Clin Pharmacol Toxicol"},{"issue":"1","key":"4016_CR120","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1080\/13880209.2022.2110128","volume":"60","author":"Q Wu","year":"2022","unstructured":"Wu Q, Duan Z, Huang L, Li Z (2022) Kuhuang injection exerts a protective effect by activating PPAR-gamma in an in vitro model of chlorpromazine-induced cholestatic liver injury constructed by tissue engineering. Pharm Biol 60(1):1679\u20131689. https:\/\/doi.org\/10.1080\/13880209.2022.2110128","journal-title":"Pharm Biol"},{"issue":"1","key":"4016_CR121","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41401-019-0266-0","volume":"41","author":"BY Xu","year":"2020","unstructured":"Xu BY, Tang XD, Chen J, Wu HB, Chen WS, Chen L (2020) Rifampicin induces clathrin-dependent endocytosis and ubiquitin-proteasome degradation of MRP2 via oxidative stress-activated PKC-ERK\/JNK\/p38 and PI3K signaling pathways in HepG2 cells. Acta Pharmacol Sin 41(1):56\u201364. https:\/\/doi.org\/10.1038\/s41401-019-0266-0","journal-title":"Acta Pharmacol Sin"},{"issue":"2","key":"4016_CR122","doi-asserted-by":"publisher","first-page":"214","DOI":"10.2133\/dmpk.25.214","volume":"25","author":"K Yamaguchi","year":"2010","unstructured":"Yamaguchi K, Murai T, Yabuuchi H, Hui SP, Kurosawa T (2010) Measurement of bile salt export pump transport activities using a fluorescent bile acid derivative. Drug Metab Pharmacokinet 25(2):214\u2013219. https:\/\/doi.org\/10.2133\/dmpk.25.214","journal-title":"Drug Metab Pharmacokinet"},{"issue":"7","key":"4016_CR123","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1124\/dmd.105.008938","volume":"34","author":"W Yamashiro","year":"2006","unstructured":"Yamashiro W, Maeda K, Hirouchi M, Adachi Y, Hu Z, Sugiyama Y (2006) Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab Dispos 34(7):1247\u20131254. https:\/\/doi.org\/10.1124\/dmd.105.008938","journal-title":"Drug Metab Dispos"},{"key":"4016_CR124","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3389\/fphar.2017.00753","volume":"8","author":"T Zhang","year":"2017","unstructured":"Zhang T, Ikejima T, Li L et al (2017) Impairment of mitochondrial biogenesis and dynamics involved in isoniazid-induced apoptosis of HepG2 cells was alleviated by p38 MAPK pathway. Front Pharmacol 8:753. https:\/\/doi.org\/10.3389\/fphar.2017.00753","journal-title":"Front Pharmacol"},{"issue":"4","key":"4016_CR125","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1080\/10408444.2020.1756219","volume":"50","author":"X Zhang","year":"2020","unstructured":"Zhang X, Jiang T, Chen D, Wang Q, Zhang LW (2020a) Three-dimensional liver models: state of the art and their application for hepatotoxicity evaluation. Crit Rev Toxicol 50(4):279\u2013309. https:\/\/doi.org\/10.1080\/10408444.2020.1756219","journal-title":"Crit Rev Toxicol"},{"key":"4016_CR126","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106634","volume":"85","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Qu X, Gao H et al (2020b) Quercetin attenuates NLRP3 inflammasome activation and apoptosis to protect INH-induced liver injury via regulating SIRT1 pathway. Int Immunopharmacol 85:106634. https:\/\/doi.org\/10.1016\/j.intimp.2020.106634","journal-title":"Int Immunopharmacol"},{"issue":"12","key":"4016_CR127","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1124\/dmd.120.000139","volume":"48","author":"J Zhu","year":"2020","unstructured":"Zhu J, Lu J, Tung HC et al (2020) Cell type-specific roles of CD38 in the interactions of isoniazid with NAD(+) in the liver. Drug Metab Dispos 48(12):1372\u20131379. https:\/\/doi.org\/10.1124\/dmd.120.000139","journal-title":"Drug Metab Dispos"},{"key":"4016_CR128","doi-asserted-by":"publisher","first-page":"1037814","DOI":"10.3389\/fphar.2022.1037814","volume":"13","author":"X Zhuang","year":"2022","unstructured":"Zhuang X, Li L, Liu T et al (2022) Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: a review. Front Pharmacol 13:1037814. https:\/\/doi.org\/10.3389\/fphar.2022.1037814","journal-title":"Front Pharmacol"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-025-04016-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00204-025-04016-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-025-04016-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T23:03:09Z","timestamp":1758582189000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00204-025-04016-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,11]]},"references-count":128,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["4016"],"URL":"https:\/\/doi.org\/10.1007\/s00204-025-04016-0","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,11]]},"assertion":[{"value":"9 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}