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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.
Acknowledgements
We are grateful to all other staffs in the Department of non-clinical research center, Guang Zhou General Pharmaceutic Research Institute for their assistances in the experiments.
Declaration of interest
All authors have no conflict of interest regarding this paper.
The project was supported by the foundation of Ministry of education and Science of Guangdong Province, People’s Republic of China (No. 2012B090600020), Ministry of Science and Technology of Guangzhou city, People’s Republic of China (No. 2011070) and Post-doctor Science Fund of Guangzhou city (No. 2012118586), People’s Republic of China.