{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:39Z","timestamp":1787028459300,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marie-Curie Sklodowska Action program","award":["833095"],"award-info":[{"award-number":["833095"]}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["861913"],"award-info":[{"award-number":["861913"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["963845"],"award-info":[{"award-number":["963845"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["858014"],"award-info":[{"award-number":["858014"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002564","name":"Alternatives Research and Development Foundation","doi-asserted-by":"publisher","award":["\/"],"award-info":[{"award-number":["\/"]}],"id":[{"id":"10.13039\/100002564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005932","name":"Center for Alternatives to Animal Testing","doi-asserted-by":"publisher","award":["\/"],"award-info":[{"award-number":["\/"]}],"id":[{"id":"10.13039\/100005932","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fund for Scientific Research-Flanders","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"Willy Gepts Fonds UZ-Brussel","award":["\/"],"award-info":[{"award-number":["\/"]}]},{"name":"Methusalem program","award":["\/"],"award-info":[{"award-number":["\/"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Drug-induced liver injury, including cholestasis, is an important clinical issue and economic burden for pharmaceutical industry and healthcare systems. However, human-relevant in vitro information on the ability of other types of chemicals to induce cholestatic hepatotoxicity is lacking. This work aimed at investigating the cholestatic potential of non-pharmaceutical chemicals using primary human hepatocytes cultured in 3D spheroids. Spheroid cultures were repeatedly (co-) exposed to drugs (cyclosporine-A, bosentan, macitentan) or non-pharmaceutical chemicals (paraquat, tartrazine, triclosan) and a concentrated mixture of bile acids for 4 weeks. Cell viability (adenosine triphosphate content) was checked every week and used to calculate the cholestatic index, an indicator of cholestatic liability. Microarray analysis was performed at specific time-points to verify the deregulation of genes related to cholestasis, steatosis and fibrosis. Despite the evident inter-donor variability, shorter exposures to cyclosporine-A consistently produced cholestatic index values below 0.80 with transcriptomic data partially supporting its cholestatic burden. Bosentan confirmed to be hepatotoxic, while macitentan was not toxic in the tested concentrations. Prolonged exposure to paraquat suggested fibrotic potential, while triclosan markedly deregulated genes involved in different types of hepatotoxicity. These results support the applicability of primary human hepatocyte spheroids to study hepatotoxicity of non-pharmaceutical chemicals in vitro.<\/jats:p>","DOI":"10.3390\/ijms222011005","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T06:38:41Z","timestamp":1634107121000},"page":"11005","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-2158","authenticated-orcid":false,"given":"V\u00e2nia","family":"Vilas-Boas","sequence":"first","affiliation":[{"name":"Entity of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-0769","authenticated-orcid":false,"given":"Eva","family":"Gijbels","sequence":"additional","affiliation":[{"name":"Entity of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaat","family":"Leroy","sequence":"additional","affiliation":[{"name":"Entity of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9730-952X","authenticated-orcid":false,"given":"Alanah","family":"Pieters","sequence":"additional","affiliation":[{"name":"Entity of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Baze","sequence":"additional","affiliation":[{"name":"KaLy-Cell, 67115 Plobsheim, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Parmentier","sequence":"additional","affiliation":[{"name":"KaLy-Cell, 67115 Plobsheim, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-8893","authenticated-orcid":false,"given":"Mathieu","family":"Vinken","sequence":"additional","affiliation":[{"name":"Entity of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1002\/hep.24229","article-title":"Drug-induced cholestasis","volume":"53","author":"Padda","year":"2011","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/hep.21359","article-title":"Hepatobiliary transporters and drug-induced cholestasis","volume":"44","author":"Meier","year":"2006","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/toxsci\/kfp088","article-title":"Toxicity testing in the 21st century: A view from the pharmaceutical industry","volume":"110","author":"MacDonald","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1006\/rtph.2000.1399","article-title":"Concordance of the toxicity of pharmaceuticals in humans and in animals","volume":"32","author":"Olson","year":"2000","journal-title":"Regul. Toxicol. Pharm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1021\/acs.chemrestox.6b00150","article-title":"Novel 3D culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates","volume":"29","author":"Lauschke","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1124\/dmd.105.007708","article-title":"Gene expression in human hepatocytes in suspension after isolation is similar to the liver of origin, is not affected by hepatocyte cold storage and cryopreservation, but is strongly changed after hepatocyte plating","volume":"34","author":"Richert","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1007\/s00204-017-1930-0","article-title":"Evaluation of transcriptomic signature as a valuable tool to study drug-induced cholestasis in primary human hepatocytes","volume":"91","author":"Parmentier","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25187","DOI":"10.1038\/srep25187","article-title":"Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease","volume":"6","author":"Bell","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1089\/ten.tec.2018.0134","article-title":"Three-dimensional spheroid primary human hepatocytes in monoculture and coculture with nonparenchymal cells","volume":"24","author":"Baze","year":"2018","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35434","DOI":"10.1038\/srep35434","article-title":"Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability","volume":"6","author":"Hendriks","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/toxsci\/kfx289","article-title":"Comparison of hepatic 2D sandwich cultures and 3D spheroids for long-term toxicity applications: A multicenter study","volume":"162","author":"Bell","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2696","DOI":"10.1096\/fj.201601375R","article-title":"Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics","volume":"31","author":"Vorrink","year":"2017","journal-title":"FASEB J."},{"key":"ref_13","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. Vitr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.toxlet.2018.06.1069","article-title":"Inter-individual differences in the susceptibility of primary human hepatocytes towards drug-induced cholestasis are compound and time dependent","volume":"295","author":"Parmentier","year":"2018","journal-title":"Toxicol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.taap.2013.10.032","article-title":"Hepatocyte-based in vitro model for assessment of drug-induced cholestasis","volume":"274","author":"Chatterjee","year":"2014","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.toxlet.2016.06.1127","article-title":"Cytotoxicity evaluation using cryopreserved primary human hepatocytes in various culture formats","volume":"258","author":"Richert","year":"2016","journal-title":"Toxicol. Lett."},{"key":"ref_17","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":"ref_18","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s00204-020-02691-9","article-title":"Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury","volume":"94","author":"Gijbels","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00204-019-02437-2","article-title":"Mechanisms and in vitro models of drug-induced cholestasis","volume":"93","author":"Gijbels","year":"2019","journal-title":"Arch. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"112165","DOI":"10.1016\/j.fct.2021.112165","article-title":"Testing in vitro tools for the prediction of cholestatic liver injury induced by non-pharmaceutical chemicals","volume":"152","author":"Gijbels","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Boedeker, W., Watts, M., Clausing, P., and Marquez, E. (2020). The global distribution of acute unintentional pesticide poisoning: Estimations based on a systematic review. BMC Public Health, 20.","DOI":"10.1186\/s12889-020-09939-0"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1111\/j.1572-0241.2000.02021.x","article-title":"Prolonged cholestasis after acute paraquat poisoning through skin absorption","volume":"95","author":"Bataller","year":"2000","journal-title":"Am. J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1021\/acs.chemrestox.9b00148","article-title":"Industrial, biocide, and cosmetic chemical inducers of cholestasis","volume":"32","author":"Gijbels","year":"2019","journal-title":"Chem. Res. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105422","DOI":"10.1016\/j.envint.2019.105422","article-title":"Cholestatic liver injury induced by food additives, dietary supplements and parenteral nutrition","volume":"136","author":"Gijbels","year":"2020","journal-title":"Environ. Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives Nutrient Sources Added to Food (2009). Scientific Opinion on the re-evaluation Tartrazine (E 102). EFSA J., 7, 1331.","DOI":"10.2903\/j.efsa.2009.1331"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1177\/0748233711433935","article-title":"Toxic effects of some synthetic food colorants and\/or flavor additives on male rats","volume":"29","author":"Moram","year":"2013","journal-title":"Toxicol. Ind. Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.toxlet.2017.03.024","article-title":"Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse","volume":"273","author":"Meyer","year":"2017","journal-title":"Toxicol. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.tox.2012.04.014","article-title":"Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity","volume":"298","author":"Axon","year":"2012","journal-title":"Toxicology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16625","DOI":"10.1074\/jbc.M602723200","article-title":"Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity","volume":"281","author":"Yamamoto","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00204-011-0769-z","article-title":"Screening of repeated dose toxicity data present in SCC(NF)P\/SCCS safety evaluations of cosmetic ingredients","volume":"86","author":"Vinken","year":"2012","journal-title":"Arch. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1080\/10937404.2017.1399306","article-title":"Triclosan exposure, transformation, and human health effects","volume":"20","author":"Weatherly","year":"2017","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1289\/ehp.10768","article-title":"Urinary concentrations of triclosan in the U.S. population: 2003\u20132004","volume":"116","author":"Calafat","year":"2008","journal-title":"Environ. Health Perspect."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1080\/15287390600631706","article-title":"Pharmacokinetics of triclosan following oral ingestion in humans","volume":"69","author":"Odham","year":"2006","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/toxsci\/kfq220","article-title":"Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening","volume":"117","author":"Rotroff","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1093\/toxsci\/kfy058","article-title":"Prediction of drug-induced hepatotoxicity using long-term stable primary hepatic 3D spheroid cultures in chemically defined conditions","volume":"163","author":"Vorrink","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s40256-014-0081-4","article-title":"Pharmacokinetic-pharmacodynamic relationships of macitentan, a new endothelin receptor antagonist, after multiple dosing in healthy Korean subjects","volume":"14","author":"Ahn","year":"2014","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_37","first-page":"860","article-title":"Pharmacokinetics of cyclosporine from conventional and new microemulsion formulations in healthy volunteers","volume":"46","author":"Gulati","year":"1998","journal-title":"J. Assoc. Phys. India"},{"key":"ref_38","first-page":"45","article-title":"Estrogenicity of the synthetic food colorants tartrazine, erythrosin B, and sudan I in an estrogen-responsive human breast cancer cell line","volume":"83","author":"Datta","year":"2008","journal-title":"J. Tenn. Acad. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1021\/acs.chemrestox.8b00112","article-title":"Adverse outcome pathway-driven analysis of liver steatosis in vitro: A case study with cyproconazole","volume":"31","author":"Luckert","year":"2018","journal-title":"Chem. Res. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e6645","DOI":"10.7717\/peerj.6645","article-title":"Identification of key genes, pathways and potential therapeutic agents for liver fibrosis using an integrated bioinformatics analysis","volume":"7","author":"Zhan","year":"2019","journal-title":"PeerJ"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00204-015-1543-4","article-title":"Experimental models of liver fibrosis","volume":"90","author":"Yanguas","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.plipres.2015.05.002","article-title":"Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research","volume":"59","author":"Willebrords","year":"2015","journal-title":"Prog. Lipid Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14297","DOI":"10.1038\/s41598-018-32722-6","article-title":"Human hepatic 3D spheroids as a model for steatosis and insulin resistance","volume":"8","author":"Kozyra","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hurrell, T., Kastrinou-Lampou, V., Fardellas, A., Hendriks, D.F.G., Nordling, \u00c5., Johansson, I., Baze, A., Parmentier, C., Richert, L., and Ingelman-Sundberg, M. (2020). Human liver spheroids as a model to study aetiology and treatment of hepatic fibrosis. Cells, 9.","DOI":"10.3390\/cells9040964"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.medici.2014.05.008","article-title":"Cyclosporine therapeutic window evaluation by Chebyshev\u2019s inequality method in kidney recipients","volume":"50","year":"2014","journal-title":"Medicina"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/toxsci\/kfx062","article-title":"Mechanistic insights in the cytotoxic and cholestatic potential of the endothelial receptor antagonists using HepaRG cells","volume":"157","author":"Burbank","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1056\/NEJMoa1213917","article-title":"Macitentan and morbidity and mortality in pulmonary arterial hypertension","volume":"369","author":"Pulido","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_48","first-page":"1465","article-title":"Effects on DNA repair in human lymphocytes exposed to the food dye tartrazine yellow","volume":"35","author":"Soares","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/toxsci\/kfq380","article-title":"Proteomics investigations of drug-induced hepatotoxicity in HepG2 cells","volume":"120","author":"Renes","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_50","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":"ref_51","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1007\/s00204-016-1893-6","article-title":"Cytochrome P450-mediated metabolism of triclosan attenuates its cytotoxicity in hepatic cells","volume":"91","author":"Wu","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2016.04.007","article-title":"Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis","volume":"302","author":"Tolosa","year":"2016","journal-title":"Toxicol. Appl Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"31259","DOI":"10.1073\/pnas.2017129117","article-title":"Triclosan leads to dysregulation of the metabolic regulator FGF21 exacerbating high fat diet-induced nonalcoholic fatty liver disease","volume":"117","author":"Yueh","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17200","DOI":"10.1073\/pnas.1419119111","article-title":"The commonly used antimicrobial additive triclosan is a liver tumor promoter","volume":"111","author":"Yueh","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4254\/wjh.v9.i4.209","article-title":"Antioxidant effects of aqueous extract of Salep on Paraquat-induced rat liver injury","volume":"9","author":"Atashpour","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"106156","DOI":"10.1016\/j.dib.2020.106156","article-title":"Dataset on transcriptomic profiling of cholestatic liver injury in an in vitro and in vivo animal model","volume":"32","author":"Gijbels","year":"2020","journal-title":"Data Brief."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11005\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:12:11Z","timestamp":1760166731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":57,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms222011005"],"URL":"https:\/\/doi.org\/10.3390\/ijms222011005","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,12]]}}}