Zebrafish: An emerging model system to study liver diseases and related drug discovery

Abstract The zebrafish has emerged as a powerful vertebrate model for studying liver‐associated disorders. Liver damage is a crucial problem in the process of drug development and zebrafish have proven to be an important tool for the high‐throughput screening of drugs for hepatotoxicity. Although the structure of the zebrafish liver differs to that of mammals, the fundamental physiologic processes, genetic mutations and manifestations of pathogenic responses to environmental insults exhibit much similarity. The larval transparency of the zebrafish is a great advantage for real‐time imaging in hepatic studies. The zebrafish has a broad spectrum of cytochrome P450 enzymes, which enable the biotransformation of drugs via similar pathways as mammals, including oxidation, reduction and hydrolysis reactions. In the present review, we appraise the various drugs, chemicals and toxins used to study liver toxicity in zebrafish and their similarities to the rodent models for liver‐related studies. Interestingly, the zebrafish has also been effectively used to study the pathophysiology of nonalcoholic and alcoholic fatty liver disease. The genetic models of liver disorders and their easy manipulation provide great opportunity in the area of drug development. The zebrafish has proven to be an influential model for the hepatic system due to its invertebrate‐like advantages coupled with its vertebrate biology. The present review highlights the pivotal role of zebrafish in bridging the gap between cell‐based and mammalian models.