title: Toxicity assessment of 7 anticancer compounds in zebrafish.
abstract: Toxicity is one of the major reasons for failure in drug development. Zebrafish, as an ideal vertebrate model, could also be used to evaluate drug toxicity. In this study, we aimed to show the predictability and highlight novel findings of toxicity in zebrafish model. Seven anticancer compounds, including triptolide (TP), gambogic acid (GA), mycophenolic acid (MPA), curcumin, auranofin, thalidomide, and taxol, were assessed in zebrafish for their toxicity. Three compounds (GA, TP, and taxol) showed highest acute lethality, with 50% lethal concentration ≈ 1 μmol/L. Missing tails, severe pericardial edema, and enlarged yolk sacs were observed in MPA-treated embryos. The development of pectoral fins was severely disturbed in thalidomide-, GA-, and TP-treated embryos. Bradycardia was observed in MPA- and thalidomide-treated groups. Our findings suggested that the zebrafish are a good model for toxicity assessment of anticancer compounds.
authors.affiliation: Institute of Translational Medicine, School of Pharmaceutical Sciences, Nanjing University of Technology, Nanjing, Jiangsu Province 210009, China. Email: mingfanghe@hotmail.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Gao
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Liu
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Wang
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: He
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007814:Larva / Q000033:anatomy & histology / Q000187:drug effects; D007928:Lethal Dose 50; D013723:Teratogens / Q000633:toxicity; D015027:Zebrafish / Q000502:physiology*
chemical_list: D000970:Antineoplastic Agents; D013723:Teratogens
keywords: acute toxicity; anticancer compounds; cardiovascular toxicity; developmental toxicity; zebrafish