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Among its various mechanisms, autophagy and apoptosis are two important signaling pathways. In this study, we used zebrafish to establish a TP\u2010induced hepatotoxicity model, and investigated the roles of autophagy and apoptosis in the progress of liver injury. Zebrafish exposed to TP showed increased mortality and malformation because of the increased drug dose and duration of exposure. Meanwhile, we found that TP induced liver injury in a time\u2010 and dose\u2010dependent manner, which was observed as a reduction in liver area, slow yolk absorption, upregulation of transaminase and local neurosis. With the application of the high\u2010content imaging system (HCIS) technique in liver 3D imaging in vivo, clear imaging of the zebrafish liver was achieved. The results showed a decrease in volume and location of necrosis in the liver after TP exposure. Increased expression of inflammatory cytokines genes tumor necrosis factor (<jats:italic>Tnf<\/jats:italic>)<jats:italic>\u03b1<\/jats:italic>, <jats:italic>Il1\u03b2<\/jats:italic> and <jats:italic>Il6<\/jats:italic> were shown, particularly <jats:italic>Tnf\u03b1<\/jats:italic>. The <jats:italic>Fas\u2010Caspase8<\/jats:italic> signaling pathway was activated. The apoptosis\u2010related gene <jats:italic>Bcl\u20102<\/jats:italic> was increased, and <jats:italic>Bax<\/jats:italic>, <jats:italic>Caspase9<\/jats:italic> and <jats:italic>Caspase3<\/jats:italic> were increased. However, autophagy related genes <jats:italic>Beclin1<\/jats:italic>, <jats:italic>Atg5<\/jats:italic>, <jats:italic>Atg3<\/jats:italic> and <jats:italic>Lc3<\/jats:italic> were increased more significantly, and the changes of <jats:italic>Beclin1<\/jats:italic> and <jats:italic>Atg5<\/jats:italic> were the most severe. This study successfully established a TP\u2010induced zebrafish hepatotoxicity model and applied the HCIS technique in a zebrafish hepatotoxicity study. The result indicated <jats:italic>Fas<\/jats:italic> might be the main target of TP\u2010induced hepatotoxicity. Autophagy played a more important role than apoptosis and was characterized by the overexpression of <jats:italic>Beclin1<\/jats:italic> and <jats:italic>Atg5<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/jat.3837","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T03:02:17Z","timestamp":1563505337000},"page":"1532-1540","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Triptolide\u2010induced hepatotoxicity via apoptosis and autophagy in zebrafish"],"prefix":"10.1002","volume":"39","author":[{"given":"Jingting","family":"Huo","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Drug Screening China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Drug Screening China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kechun","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung\u2010Der","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology Chung Yuan Christian University  Chung\u2010Li Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-0822","authenticated-orcid":false,"given":"Zhenzhou","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Drug Screening China Pharmaceutical University  Nanjing China"},{"name":"Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Drug Screening China Pharmaceutical University  Nanjing China"},{"name":"Center for Drug Research and Development Guangdong Pharmaceutical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/138620709789383240"},{"key":"e_1_2_8_3_1","first-page":"e58670","article-title":"Using high content imaging to quantify target engagement in adherent cells","volume":"141","author":"Axelsson H.","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/2472555219830087"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.01.012"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092508"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020376"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.44"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581814523142"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199737"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-018-9447-8"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2008.09.033"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.06.006"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-016-1504-3"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.09.042"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2008.03.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0396.2007.00752.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.185"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfx144"},{"key":"e_1_2_8_20_1","first-page":"1","article-title":"A systematic review about the efficacy and safety of Tripterygium wilfordii Hook.f. 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