title: A rapid assessment for predicting drug-induced hepatotoxicity using zebrafish.
abstract: BACKGROUND
  Zebrafish have been used as a model to access drug-induced hepatotoxicity. However, individual differences occur in the liver development of zebrafish.
  
  
  METHODS
  We used a transgenic line of zebrafish that expressed enhanced green fluorescent protein (EGFP) in the liver and then used a calculation of the liver index area, a potentially new endpoint of hepatotoxicity, to evaluate drug-induced liver injury. To further validate the reliability of the liver area index as a quick evaluation of zebrafish liver function damage, the liver area index level was correlated with hepatic transaminase activities using the Pearson correlation coefficient and confirmed by histopathology.
  
  
  RESULTS
  Zebrafish larvae treated with high doses of the known mammalian hepatotoxic drugs carbaryl, isoniazide, and pyrazinamide showed significantly decreased liver area index levels, which are suggestive of liver injury and correspond with the higher alanine transaminase (ALT) and aspartate transaminase (AST) activities and histological liver alterations. The results showed a significant negative correlation between the degree of liver injury and the liver area index level.
  
  
  CONCLUSIONS
  Our data support the use of the liver area index as a reliable and comparable indicator to screen hepatotoxic agents using the zebrafish model.
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Han
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: He
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Chen
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Sun
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China.
authors.forename: Rongchun
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, 32023, Taiwan.
authors.forename: Chung-Der
authors.initials: CD
authors.lastname: Hsiao
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Shandong Provincial Engineering Laboratory for Biological Testing Technology, Key Laboratory for Biosensor of Shandong Province, 19 Keyuan Road, Lixia District, Jinan 250014, Shandong Province, PR China. Electronic address: hliukch@sdas.org.
authors.forename: Kechun
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D012721:Carbaryl / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007538:Isoniazid / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D013997:Time Factors; D015027:Zebrafish
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D012721:Carbaryl; D007538:Isoniazid
keywords: Animal model; Hepatotoxic assessment; Liver area index; Liver toxicity; Methods; Zebrafish