{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:48:58Z","timestamp":1793674138022,"version":"4.5.1"},"reference-count":67,"publisher":"SAGE Publications","issue":"7-8","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM122576"],"award-info":[{"award-number":["R35 GM122576"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:p>\n                    Drug-induced liver injury (DILI) remains a major concern in drug development from a patient safety perspective because it is the leading cause of acute liver failure. One mechanism of DILI is altered bile acid homeostasis and involves several hepatic bile acid transporters. Functional impairment of some hepatic bile acid transporters by drugs, disease, or genetic mutations may lead to toxic accumulation of bile acids within hepatocytes and increase DILI susceptibility. This review focuses on the role of hepatic bile acid transporters in DILI. Model systems, primarily\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and modeling tools, such as DILIsym, used in assessing transporter-mediated DILI are discussed. Due to species differences in bile acid homeostasis and drug-transporter interactions, key aspects and challenges associated with the use of preclinical animal models for DILI assessment are emphasized. Learnings are highlighted from three case studies of hepatotoxic drugs: troglitazone, tolvaptan, and tyrosine kinase inhibitors (dasatinib, pazopanib, and sorafenib). The development of advanced\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    models and novel biomarkers that can reliably predict DILI is critical and remains an important focus of ongoing investigations to minimize patient risk for liver-related adverse reactions associated with medication use.\n                  <\/jats:p>","DOI":"10.1177\/01926233231212255","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T05:46:58Z","timestamp":1700459218000},"page":"405-413","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity"],"prefix":"10.1177","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-1917","authenticated-orcid":false,"given":"Chitra","family":"Saran","sequence":"first","affiliation":[{"name":"Transporter Sciences, Pharmacokinetics, Dynamics, Metabolism, and Bioanalytics (PDMB), Merck &amp; Co., Inc., West Point, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim L. R.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R900012-JLR200."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2605."},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.04.001."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0105-0."},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kft176."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.9b00262."},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1222."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.119073."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfx284."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00539.2005."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120023."},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02804-4."},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.246033."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.08.002."},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707235."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2020.1779701."},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/01926233231171101."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1701."},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1699."},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1717."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1115."},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.66."},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.997."},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23147947."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00310.2017."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.04.036."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.118.114827."},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.054189."},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22532."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2020.05.001."},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2619."},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2015.12.017."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0246."},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3644."},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.02.002."},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2014.158."},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.114667."},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.05.011."},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.78."},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfz079."},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.comtox.2022.100224."},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0300-483x(01)00460-7."},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv231."},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.120.000086."},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2018.04.018."},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2006.01.004."},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-18174-z."},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.3109\/03602530903491881."},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.067629."},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.086785."},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.118.083907."},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2007."},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-013-0048-4."},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7453406."},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.983075."},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19082367."},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.644342."},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2044."},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3551."},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00367."},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2018.04.010."},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq269."},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.121.000828."},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1415145."},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kft221."},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016717."},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-013-1078-5."}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/01926233231212255","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/01926233231212255","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/01926233231212255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:43:11Z","timestamp":1777653791000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/01926233231212255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10]]},"references-count":67,"journal-issue":{"issue":"7-8","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1177\/01926233231212255"],"URL":"https:\/\/doi.org\/10.1177\/01926233231212255","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10]]}}}