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Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
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Clinically approved iron chelators influence zebrafish mortality, hatching morphology and cardiac function.
Jasmine L Hamilton1, Azadeh Hatef2, Muhammad Imran ul-Haq1
1The Centre for Blood Research, Department of Pathology and Laboratory Medicine, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada.
Plos One
|October 21, 2014
Summary
Iron chelators like deferasirox (ICL-670) and deferiprone (L1) show toxicity in zebrafish embryos, while desferrioxamine (DFO) does not. ICL-670 also impacts adult zebrafish cardiac function, highlighting developmental toxicity concerns.
Area of Science:
- Pharmacology
- Developmental Biology
- Toxicology
Background:
- Iron chelation therapy is crucial for treating iron overload but associated with toxicities.
- Limited data exists on iron chelator effects on embryonic development.
- Zebrafish embryos offer a transparent and rapidly developing model for toxicity studies.
Purpose of the Study:
- To assess and compare the developmental toxicity of three standard iron chelators: desferrioxamine (DFO), deferasirox (ICL-670), and deferiprone (L1).
- To investigate potential toxicity in adult zebrafish to differentiate embryo-specific effects.
Main Methods:
- Zebrafish embryos were exposed to DFO, ICL-670, and L1 via direct soaking.
- Effects on mortality, hatching, and morphology were monitored over 96 hours post-fertilization (hpf).
- Adult zebrafish were injected with chelators to assess cardiac function and gene expression.
Main Results:
- DFO showed no significant toxicity in embryos or adults.
- ICL-670 significantly increased embryo mortality and caused morphological defects, and also increased adult heart rate and cardiac output.
- L1 caused morphological defects in embryos but not in adults.
Conclusions:
- Iron chelators exhibit differential toxicity during early development.
- ICL-670 demonstrates significant developmental and adult cardiac toxicity.
- This study provides crucial initial insights into iron chelator toxicity mechanisms in early development.
