title: A Zebrafish Thrombosis Model for Assessing Antithrombotic Drugs.
abstract: Thrombosis is a leading cause of death and the development of effective and safe therapeutic agents for thrombotic diseases has been proven challenging. In this study, taking advantage of the transparency of larval zebrafish, we developed a larval zebrafish thrombosis model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days post fertilization) were treated with phenylhydrazine (PHZ) and a testing drug for 24 h. Tested drugs were administered into the zebrafish either by direct soaking or circulation microinjection. Antithrombotic efficacy was quantitatively evaluated based on our previously patented technology characterized as an image analysis of the heart red blood cells stained with O-dianisidine staining. Zebrafish at 2 dpf treated with PHZ at a concentration of 1.5 μM for a time period of 24 h were determined as the optimum conditions for the zebrafish thrombosis model development. Induced thrombosis in zebrafish was visually confirmed under a dissecting stereomicroscope and quantified by the image assay. All 6 human antithrombotic drugs (aspirin, clopidogrel, diltiazem hydrochloride injection, xuanshuantong injection, salvianolate injection, and astragalus injection) showed significant preventive and therapeutic effects on zebrafish thrombosis (p < 0.05, p < 0.01, & p < 0.001) in this zebrafish thrombosis model. The larval zebrafish thrombosis model developed and validated in this study could be used for in vivo thrombosis studies and for rapid screening and efficacy assessment of antithrombotic drugs.
authors.affiliation: 1 Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Wenzhou Medical University , Wenzhou, People's Republic of China .|2 Hunter Biotechnology, Inc. , Hangzhou City, People's Republic of China .|3 Innovation Team of Drug Safety Evaluation, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals , Hangzhou, People's Republic of China .
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: 2 Hunter Biotechnology, Inc. , Hangzhou City, People's Republic of China .
authors.forename: Hong-Cui
authors.initials: HC
authors.lastname: Liu
authors.affiliation: 2 Hunter Biotechnology, Inc. , Hangzhou City, People's Republic of China .
authors.forename: Sheng-Ya
authors.initials: SY
authors.lastname: Guo
authors.affiliation: 2 Hunter Biotechnology, Inc. , Hangzhou City, People's Republic of China .
authors.forename: Bo
authors.initials: B
authors.lastname: Xia
authors.affiliation: 2 Hunter Biotechnology, Inc. , Hangzhou City, People's Republic of China .
authors.forename: Ru-Shun
authors.initials: RS
authors.lastname: Song
authors.affiliation: 2 Hunter Biotechnology, Inc. , Hangzhou City, People's Republic of China .
authors.forename: Qiao-Cong
authors.initials: QC
authors.lastname: Lao
authors.affiliation: 3 Innovation Team of Drug Safety Evaluation, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals , Hangzhou, People's Republic of China .|4 Center of Safety Evaluation , Zhejiang Academy of Medical Sciences, Hangzhou, People's Republic of China .
authors.forename: Yao-Xian
authors.initials: YX
authors.lastname: Xuan
authors.affiliation: 1 Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Wenzhou Medical University , Wenzhou, People's Republic of China .|2 Hunter Biotechnology, Inc. , Hangzhou City, People's Republic of China .|3 Innovation Team of Drug Safety Evaluation, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals , Hangzhou, People's Republic of China .
authors.forename: Chun-Qi
authors.initials: CQ
authors.lastname: Li
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D008845:Microinjections; D013927:Thrombosis / Q000188:drug therapy*; D015027:Zebrafish
chemical_list: D005343:Fibrinolytic Agents