Zhang Yun, Han Liwen, He Qiuxia, Chen Weiyun, Sun Chen, Wang Xue, Chen Xiqiang, Wang Rongchun, Hsiao Chung-Der, Liu Kechun
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.
Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, 32023, Taiwan.
J Pharmacol Toxicol Methods. 2017 Mar-Apr;84:102-110. doi: 10.1016/j.vascn.2016.12.002. Epub 2016 Dec 8.
Zebrafish have been used as a model to access drug-induced hepatotoxicity. However, individual differences occur in the liver development of zebrafish.
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.
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.
Our data support the use of the liver area index as a reliable and comparable indicator to screen hepatotoxic agents using the zebrafish model.
斑马鱼已被用作评估药物诱导肝毒性的模型。然而，斑马鱼的肝脏发育存在个体差异。
我们使用了一种在肝脏中表达增强型绿色荧光蛋白（EGFP）的转基因斑马鱼品系，然后通过计算肝脏指数面积（一种潜在的肝毒性新终点）来评估药物诱导的肝损伤。为了进一步验证肝脏面积指数作为快速评估斑马鱼肝功能损害的可靠性，使用皮尔逊相关系数将肝脏面积指数水平与肝转氨酶活性相关联，并通过组织病理学进行确认。
用已知的哺乳动物肝毒性药物西维因、异烟肼和吡嗪酰胺高剂量处理的斑马鱼幼虫肝脏面积指数水平显著降低，这表明肝脏受到损伤，并且与较高的丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性以及肝脏组织学改变相对应。结果显示肝损伤程度与肝脏面积指数水平之间存在显著负相关。
我们的数据支持使用肝脏面积指数作为一种可靠且可比的指标，以斑马鱼模型筛选肝毒性药物。
