title: A zebrafish phenotypic assay for assessing drug-induced hepatotoxicity.
abstract: BACKGROUND
  Numerous studies have confirmed that zebrafish and mammalian toxicity profiles are strikingly similar and the transparency of larval zebrafish permits direct in vivo assessment of drug toxicity including hepatotoxicity in zebrafish.
  
  
  METHODS
  Hepatotoxicity of 6 known mammalian hepatotoxic drugs (acetaminophen [APAP], aspirin, tetracycline HCl, sodium valproate, cyclophosphamide and erythromycin) and 2 non-hepatotoxic compounds (sucrose and biotin) were quantitatively assessed in larval zebrafish using three specific phenotypic endpoints of hepatotoxicity: liver degeneration, changes in liver size and yolk sac retention. Zebrafish liver degeneration was originally screened visually, quantified using an image-based morphometric analysis and confirmed by histopathology.
  
  
  RESULTS
  All the tested mammalian hepatotoxic drugs induced liver degeneration, reduced liver size and delayed yolk sac absorption in larval zebrafish, whereas the non-hepatotoxic compounds did not have observable adverse effect on zebrafish liver. The overall prediction success rate for hepatotoxic drugs and non-hepatotoxic compounds in zebrafish was 100% (8/8) as compared with mammalian results, suggesting that hepatotoxic drugs in mammals also caused similar hepatotoxicity in zebrafish.
  
  
  CONCLUSIONS
  Larval zebrafish phenotypic assay is a highly predictive animal model for rapidly in vivo assessment of compound hepatotoxicity. This convenient, reproducible animal model saves time and money for drug discovery and can serve as an intermediate step between cell-based evaluation and conventional animal testing of hepatotoxicity.
authors.affiliation: Hunter Biotechnology, Inc., Transfarland, Hangzhou, Zhejiang Province 311231, PR China.
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: He
authors.forename: Sheng-Ya
authors.initials: SY
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Jun-Jing
authors.initials: JJ
authors.lastname: Zhu
authors.forename: Yun-Xiang
authors.initials: YX
authors.lastname: Chen
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Huang
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Gao
authors.forename: Qiao-Xiang
authors.initials: QX
authors.lastname: Dong
authors.forename: Yao-Xian
authors.initials: YX
authors.lastname: Xuan
authors.forename: Chun-Qi
authors.initials: CQ
authors.lastname: Li
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000235:genetics*; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D018675:Toxicity Tests / Q000379:methods; D015027:Zebrafish