Zebrafish as a model for drug induced liver injury: state of the art and beyond

Abstract

Zebrafish as a preclinical drug induced liver injury (DILI) model provides multiple advantages ranging from ease of breeding and maintenance, availability of different strains and transgenic fish amenable to study liver function, and highly conserved liver structure and function with the human liver. In this review, the authors have aimed to provide an account of the metabolic enzymes that take roles in drug detoxification in both human and zebrafish in a comparative manner and exemplify several recent models in studying liver functionality. Moreover, the authors emphasize the difficulties associated with studying idiosyncratic DILI in preclinical models and propose that zebrafish could be an important complement to mice in testing functions of genes that are associated with DILI with respect to different drugs in human genome-wide association studies (GWAS) Catalog. Finally, this review highlights the state-of-the-art in the development of novel transgenic reporter strains that can be used to study degree and molecular mechanisms of hepatotoxicity caused by drugs in zebrafish. All of these will help researchers to use effectively the available resources in the zebrafish DILI models, while advocating potential leads that can be taken to provide advancements in a better understanding and treatment of DILI.

Keywords

• drug induced liver injury
• zebrafish
• reporter lines
• genome-wide association studies