Yun Zhang1, Liwen Han1, Qiuxia He1, Weiyun Chen1, Chen Sun1, Xue Wang1, Xiqiang Chen1, Rongchun Wang1, Chung-Der Hsiao2, Kechun Liu3. 1. 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. 2. Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, 32023, Taiwan. 3. 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.
Abstract
INTRODUCTION: 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. DISCUSSION: Our data support the use of the liver area index as a reliable and comparable indicator to screen hepatotoxic agents using the zebrafish model.
INTRODUCTION: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 mammalianhepatotoxic 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. DISCUSSION: 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: Steven Cassar; Isaac Adatto; Jennifer L Freeman; Joshua T Gamse; Iñaki Iturria; Christian Lawrence; Arantza Muriana; Randall T Peterson; Steven Van Cruchten; Leonard I Zon Journal: Chem Res Toxicol Date: 2019-11-16 Impact factor: 3.739
Authors: Marija Mojicevic; Paul M D'Agostino; Aleksandar Pavic; Sandra Vojnovic; Ramsankar Senthamaraikannan; Branka Vasiljevic; Tobias A M Gulder; Jasmina Nikodinovic-Runic Journal: Microbiologyopen Date: 2020-01-28 Impact factor: 3.139