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

National University of Singapore, Department of Biological Sciences, Singapore.
Expert Opinion on Drug Metabolism & Toxicology (Impact Factor: 2.83). 02/2011; 7(5):579-89. DOI: 10.1517/17425255.2011.562197
Source: PubMed


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.

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Available from: Zhiyuan Gong, Nov 19, 2015
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    • "The zebrafish, a well-characterized vertebrate model, are applying to the fields of molecular 243 genetics and developmental biology, which can use as an increasingly popular pre-clinical 244 testing model organism in drug toxicology and screen for its similar genes and complex 245 organs found in mammals16171819. The conversion of drugs is related to their activation and 246 inactivation in vivo. "
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    • "An alternative approach is the use of the whole liver system of zebrafish larvae, with unique advantages for early medium throughput in vivo toxicity screening that can precede preclinical toxicity testing. Zebrafish larvae are only 1–4 mm long and can live in a single well of a 96-well plate for several days (Sukardi et al., 2011). "
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