{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:34:01Z","timestamp":1791545641035,"version":"4.3.4"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100009013","name":"Jimei University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014769","name":"Jinggangshan University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31872562"],"award-info":[{"award-number":["31872562"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31900597"],"award-info":[{"award-number":["31900597"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32072969"],"award-info":[{"award-number":["32072969"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860282"],"award-info":[{"award-number":["81860282"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20192ACB21013"],"award-info":[{"award-number":["20192ACB21013"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20204BCJL23043"],"award-info":[{"award-number":["20204BCJL23043"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.tox.2021.152951","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T22:16:00Z","timestamp":1631657760000},"page":"152951","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":17,"special_numbering":"C","title":["Lenvatinib exposure induces hepatotoxicity in zebrafish via inhibiting Wnt signaling"],"prefix":"10.1016","volume":"462","author":[{"given":"Ling","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanbo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fasheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meile","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghua","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjun","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8463-4996","authenticated-orcid":false,"given":"Zigang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.tox.2021.152951_bib0005","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1016\/S0021-9258(18)61588-1","article-title":"Rat ceruloplasmin. Molecular cloning and gene expression in liver, choroid plexus, yolk sac, placenta, and testis","volume":"262","author":"Aldred","year":"1987","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.tox.2021.152951_bib0010","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1097\/WOX.0b013e3182439613","article-title":"Oxidative stress and antioxidant defense","volume":"5","author":"Birben","year":"2012","journal-title":"The World Allergy Organization journal"},{"issue":"1\u20132","key":"10.1016\/j.tox.2021.152951_bib0015","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.mce.2013.01.021","article-title":"Prolactin regulates transcription of the ion uptake Na+\/Cl- cotransporter (ncc) gene in zebrafish gill","volume":"369","author":"Breves","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"issue":"1","key":"10.1016\/j.tox.2021.152951_bib0020","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.bbrc.2016.03.051","article-title":"Noncanonical function of threonyl-tRNA synthetase regulates vascular development in zebrafish","volume":"473","author":"Cao","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"7","key":"10.1016\/j.tox.2021.152951_bib0025","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/j.celrep.2019.01.061","article-title":"Germline stem cells drive ovary regeneration in zebrafish","volume":"26","author":"Cao","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.tox.2021.152951_bib0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2020.113926","article-title":"Exposure to diclofop-methyl induces cardiac developmental toxicity in zebrafish embryos","volume":"259","author":"Cao","year":"2020","journal-title":"Environ. Pollut."},{"key":"10.1016\/j.tox.2021.152951_bib0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2020.128611","article-title":"Carboxyl graphene oxide nanoparticles induce neurodevelopmental defects and locomotor disorders in zebrafish larvae","volume":"270","author":"Cao","year":"2021","journal-title":"Chemosphere"},{"issue":"4","key":"10.1016\/j.tox.2021.152951_bib0040","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1002\/hep.28763","article-title":"Upstream regulators of hepatic Wnt\/\u03b2-catenin activity control liver metabolic zonation, development, and regeneration","volume":"64","author":"Clerbaux","year":"2016","journal-title":"Hepatology"},{"issue":"3","key":"10.1016\/j.tox.2021.152951_bib0045","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.cell.2006.10.018","article-title":"Wnt\/beta-catenin signaling in development and disease","volume":"127","author":"Clevers","year":"2006","journal-title":"Cell"},{"issue":"5","key":"10.1016\/j.tox.2021.152951_bib0050","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1002\/hep.22837","article-title":"Exogenous thioredoxin prevents ethanol-induced oxidative damage and apoptosis in mouse liver","volume":"49","author":"Cohen","year":"2009","journal-title":"Hepatology"},{"issue":"1","key":"10.1016\/j.tox.2021.152951_bib0055","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s12012-015-9315-1","article-title":"FGF2 prevents sunitinib-induced cardiotoxicity in zebrafish and cardiomyoblast H9c2 cells","volume":"16","author":"Cui","year":"2016","journal-title":"Cardiovasc. Toxicol."},{"key":"10.1016\/j.tox.2021.152951_bib0060","unstructured":"FDA, U. LENVIMA Pharmacology Review. Available from https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2015\/206947Orig1s000PharmR.pdf."},{"issue":"2","key":"10.1016\/j.tox.2021.152951_bib0065","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0012-1606(02)00017-9","article-title":"Formation of the digestive system in zebrafish. I. Liver morphogenesis","volume":"253","author":"Field","year":"2003","journal-title":"Dev. Biol."},{"issue":"19\u201320","key":"10.1016\/j.tox.2021.152951_bib0070","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1007\/s00018-006-6095-6","article-title":"The Foxa family of transcription factors in development and metabolism","volume":"63","author":"Friedman","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"issue":"1","key":"10.1016\/j.tox.2021.152951_bib0075","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.vascn.2012.10.003","article-title":"A zebrafish phenotypic assay for assessing drug-induced hepatotoxicity","volume":"67","author":"He","year":"2013","journal-title":"J. Pharmacol. Toxicol. Methods"},{"issue":"10","key":"10.1016\/j.tox.2021.152951_bib0080","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1038\/s41596-020-0376-7","article-title":"Combined whole-mount fluorescence in situ hybridization and antibody staining in zebrafish embryos and larvae","volume":"15","author":"He","year":"2020","journal-title":"Nat. Protoc."},{"issue":"6242","key":"10.1016\/j.tox.2021.152951_bib0085","doi-asserted-by":"crossref","first-page":"aaa6071","DOI":"10.1126\/science.aaa6071","article-title":"HEART DEVELOPMENT. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts","volume":"348","author":"Jain","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.tox.2021.152951_bib0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2020.125941","article-title":"Thiophanate-methyl induces severe hepatotoxicity in zebrafish","volume":"248","author":"Jia","year":"2020","journal-title":"Chemosphere"},{"issue":"10126","key":"10.1016\/j.tox.2021.152951_bib0095","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(18)30207-1","article-title":"Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial","volume":"391","author":"Kudo","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.tox.2021.152951_bib0100","first-page":"1656","article-title":"Astaxanthin protects ARPE-19 cells from oxidative stress via upregulation of Nrf2-regulated phase II enzymes through activation of PI3K\/Akt","volume":"19","author":"Li","year":"2013","journal-title":"Mol. Vis."},{"key":"10.1016\/j.tox.2021.152951_bib0105","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.watres.2015.10.040","article-title":"Critical review on the stability of illicit drugs in sewers and wastewater samples","volume":"88","author":"McCall","year":"2016","journal-title":"Water Res."},{"issue":"12","key":"10.1016\/j.tox.2021.152951_bib0110","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1242\/dev.001230","article-title":"Repression of Wnt\/beta-catenin signaling in the anterior endoderm is essential for liver and pancreas development","volume":"134","author":"McLin","year":"2007","journal-title":"Development"},{"issue":"10","key":"10.1016\/j.tox.2021.152951_bib0115","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1211\/jpp.60.10.0013","article-title":"Astaxanthin, a dietary carotenoid, protects retinal cells against oxidative stress in-vitro and in mice in-vivo","volume":"60","author":"Nakajima","year":"2008","journal-title":"J. Pharm. Pharmacol."},{"issue":"20","key":"10.1016\/j.tox.2021.152951_bib0120","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1093\/emboj\/20.20.5587","article-title":"Oxidative stress inhibits the repair of photodamage to the photosynthetic machinery","volume":"20","author":"Nishiyama","year":"2001","journal-title":"EMBO J."},{"issue":"11","key":"10.1016\/j.tox.2021.152951_bib0125","doi-asserted-by":"crossref","first-page":"5973","DOI":"10.21873\/anticanres.13802","article-title":"Antiproliferative effect of lenvatinib on human liver cancer cell lines in vitro and in vivo","volume":"39","author":"Ogasawara","year":"2019","journal-title":"Anticancer Res."},{"key":"10.1016\/j.tox.2021.152951_bib0130","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1743-7075-7-18","article-title":"Astaxanthin decreased oxidative stress and inflammation and enhanced immune response in humans","volume":"7","author":"Park","year":"2010","journal-title":"Nutr. Metab. (Lond.)"},{"key":"10.1016\/j.tox.2021.152951_bib0135","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1471-213X-8-27","article-title":"Crucial role of zebrafish prox1 in hypothalamic catecholaminergic neurons development","volume":"8","author":"Pistocchi","year":"2008","journal-title":"BMC Dev. Biol."},{"key":"10.1016\/j.tox.2021.152951_bib0140","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.chemosphere.2019.05.159","article-title":"Hepatotoxicity of tricyclazole in zebrafish (Danio rerio)","volume":"232","author":"Qiu","year":"2019","journal-title":"Chemosphere"},{"issue":"10","key":"10.1016\/j.tox.2021.152951_bib0145","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS function in redox signaling and oxidative stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"issue":"7","key":"10.1016\/j.tox.2021.152951_bib0150","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1056\/NEJMoa1406470","article-title":"Lenvatinib versus placebo in radioiodine-refractory thyroid cancer","volume":"372","author":"Schlumberger","year":"2015","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"10.1016\/j.tox.2021.152951_bib0155","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/hep.21543","article-title":"\"Zebrafish and the understanding of liver development: the emerging role of the Wnt pathway in liver biology","volume":"45","author":"Shackel","year":"2007","journal-title":"Hepatology"},{"issue":"5","key":"10.1016\/j.tox.2021.152951_bib0160","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1093\/cvr\/cvz006","article-title":"Ponatinib-induced cardiotoxicity: delineating the signalling mechanisms and potential rescue strategies","volume":"115","author":"Singh","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.tox.2021.152951_bib0165","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.fsi.2019.02.008","article-title":"Neutrophil plays critical role during Edwardsiella piscicida immersion infection in zebrafish larvae","volume":"87","author":"Wang","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"10.1016\/j.tox.2021.152951_bib0170","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2019.124753","article-title":"Characterization of boscalid-induced oxidative stress and neurodevelopmental toxicity in zebrafish embryos","volume":"238","author":"Wang","year":"2020","journal-title":"Chemosphere"},{"key":"10.1016\/j.tox.2021.152951_bib0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2019.124423","article-title":"Immunotoxicity and transcriptome analysis of zebrafish embryos in response to glufosinate-ammonium exposure","volume":"236","author":"Xiong","year":"2019","journal-title":"Chemosphere"},{"key":"10.1016\/j.tox.2021.152951_bib0180","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/1471-2164-8-201","article-title":"Prevalence of the EH1 Groucho interaction motif in the metazoan Fox family of transcriptional regulators","volume":"8","author":"Yaklichkin","year":"2007","journal-title":"BMC Genomics"},{"issue":"1","key":"10.1016\/j.tox.2021.152951_bib0185","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s00128-016-1833-4","article-title":"Toxic effects of bromothalonil and flutolanil on multiple developmental stages in zebrafish","volume":"97","author":"Yang","year":"2016","journal-title":"Bull. Environ. Contam. Toxicol."},{"key":"10.1016\/j.tox.2021.152951_bib0190","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jhazmat.2015.12.055","article-title":"Toxic effects of thifluzamide on zebrafish (Danio rerio)","volume":"307","author":"Yang","year":"2016","journal-title":"J. Hazard. Mater."},{"issue":"3","key":"10.1016\/j.tox.2021.152951_bib0195","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ygcen.2006.10.009","article-title":"The effects of the members of growth hormone family knockdown in zebrafish development","volume":"150","author":"Zhu","year":"2007","journal-title":"Gen. Comp. Endocrinol."}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X21002742?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X21002742?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T23:47:45Z","timestamp":1759535265000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X21002742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":39,"alternative-id":["S0300483X21002742"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2021.152951","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Lenvatinib exposure induces hepatotoxicity in zebrafish via inhibiting Wnt signaling","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2021.152951","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"152951"}}