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High-throughput Measurement of Gut Transit Time Using Larval Zebrafish
Published on: October 23, 2018
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A high-throughput method for predicting drug effects on gut transit time using larval zebrafish
Steven Cassar1, Xin Huang1, Todd Cole1
1Abbvie, North Chicago, IL, USA.
Journal of Pharmacological and Toxicological Methods
|August 28, 2015
Summary
This study introduces a rapid zebrafish assay to predict gastrointestinal (GI) safety issues in mammals. The method efficiently screens drug candidates, accelerating discovery and reducing animal testing.
Area of Science:
- Pharmacology
- Toxicology
- Developmental Biology
Background:
- Zebrafish share significant gastrointestinal (GI) tract similarities with mammals.
- GI intolerance is a critical safety concern in drug development.
- Current mammalian GI liability tests are resource-intensive.
Purpose of the Study:
- To develop a high-throughput method for predicting mammalian GI safety using larval zebrafish.
- To assess the utility of zebrafish as a model for GI transit time studies.
Main Methods:
- Larval zebrafish (7 days post fertilization) were fed fluorescent food.
- Larvae were exposed to test compounds in 96-well plates.
- Fecal accumulation, indicating GI transit, was tracked via fluorescence over 24 hours.
Main Results:
- Known GI drugs altered zebrafish GI transit time, with some accelerating and others decelerating it.
- The assay demonstrated dose-dependent effects with atropine.
- The method showed high positive predictive value for mammalian GI effects using 24 compounds.
Conclusions:
- An efficient assay for predicting mammalian GI transit liabilities in larval zebrafish was developed.
- This assay allows rapid screening of numerous compounds, prioritizing safe drug candidates.
- The method supports the 3 Rs (Replacement, Reduction, Refinement) in animal testing and expedites drug discovery.
