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Study on early biomarkers of zebrafish liver injury induced by acetaminophen
Authors:Qiuping Guo  Baiquan Xiao  Hong Zhang  Xialing Lei  Huiyu Ou
Affiliation:1. Postdoctoral Workstation of Shanghai University of Traditional Chinese Medicine, Shanghai, China,;2. Postdoctoral Workstation of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine CO., LTD, Guangzhou, China, and;3. Guangzhou General Pharmaceutical Research Institute Drug Non Clinical Evaluation and Research Center, Guangzhou, China
Abstract:The aim of this study was to systematically study zebrafish model to predict drug-induced liver injury (DILI) with the drug acetaminophen (APAP) and find the sensitive early biomarkers. The concentration–toxicity relationship was determined at concentrations 1, 2, 4, 8, 16?mmol/L of APAP. APAP caused a concentration-dependent mortality of zebrafish. APAP caused a time-dependent mortality. Mild to severe vacuolar degeneration of liver cells were observed. APAP increased serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and xanthine oxidase (XOD) levels significantly, while it delevated argininosuccinic acid lyase (ASAL) and total bile acid (TBA) levels. TBA and ASAL were more sensitive than ALT in this process. Zebrafish may be a convenient, practical and valuable biological model to predict DILI.
Keywords:Acetaminophen  biomarker  liver damage  toxicity  zebrafish
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