Zebrafish for drug toxicity screening: bridging the in vitro cell-based models and in vivo mammalian models

Abstract

Introduction: Over the past decade, zebrafish have been tasked to play important roles from modeling human diseases to finding cures for them. Inadvertently, these fish now find themselves swimming along the drug development pipeline. A number of studies have been conducted to see if these small fish are up to the task of drug toxicity testing, an important rite of passage along the pharmaceutical pipeline.

Areas covered: This review covers the recent publications (2008 – 2010) on the state-of-the-art applications that couple advanced technologies with the unique advantages of zebrafish for drug toxicity screening. The paper looks at the several automated high-throughput platforms that have been developed for zebrafish teratogenicity, cardiotoxicity and neuro-sensory organ toxicity assays over the past 3 years as well as the important studies related to metabolism and biotransformation of selected drugs that have been initiated. This paper also reviews their mechanistic and predictive omics applications.

Expert opinion: While there have been a number of developments over the past 3 years and indeed over the last 10 years, challenges and limitations still exist, which, unless overcome, will prevent zebrafish from truly reaching their full potential as a drug toxicological model. That being said, recent developments have suggested that zebrafish could play a role in bridging the gap between in vitro cell-based models and in vivo mammalian models.

Keywords::

• cardiotoxicity
• drug toxicity screening
• high-throughput phenotype-based screening
• neuro-sensory organ toxicity
• omics applications
• safety pharmacology
• teratogenicity
• zebrafish

Notes

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