A rapid assessment for predicting drug-induced hepatotoxicity using zebrafish.

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.