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Small Molecule Screening and Toxicity Testing in Early-stage Zebrafish Larvae
Published on: March 7, 2025
Developmental toxicity of dextromethorphan in zebrafish embryos/larvae
Zheng Xu1, Frederick E Williams, Ming-Cheh Liu
1Department of Pharmacology, College of Pharmacy, The University of Toledo, Toledo, OH 43606 USA.
Journal of Applied Toxicology : JAT
|August 26, 2010
Summary
Dextromethorphan exposure in zebrafish embryos at 24 hours post fertilization caused higher mortality and severe developmental defects. Early exposure to this common cough medicine ingredient poses significant risks to early development.
Area of Science:
- Developmental toxicology
- Pharmacology
- Zebrafish model systems
Background:
- Dextromethorphan is a common ingredient in over-the-counter cough and cold remedies.
- The safety and efficacy of dextromethorphan in infants and young children require further investigation.
Purpose of the Study:
- To investigate the potential toxicity of dextromethorphan during embryonic and larval development using a zebrafish model.
- To assess the impact of early-life exposure to dextromethorphan on zebrafish development.
Main Methods:
- Zebrafish embryos were exposed to dextromethorphan at 24, 48, and 72 hours post fertilization (hpf).
- Mortality rates, cardiac function (bradycardia, blood flow), and morphological abnormalities were assessed.
- Gene expression analysis (RT-PCR) was performed for specific metabolic enzymes.
Main Results:
- Exposure at 24 hpf resulted in significantly higher mortality and dose-dependent toxicity compared to later exposure times.
- Observed effects included cardiac and yolk sac edema, craniofacial malformations, lordosis, uninflated swim bladders, and missing gills.
- Developmental stage-dependent expression of SULT3 ST1 and SULT3 ST3 mRNA was detected.
Conclusions:
- Early embryonic exposure (24 hpf) to dextromethorphan is associated with increased mortality and severe developmental toxicity in zebrafish.
- The findings suggest that the timing of exposure is critical in determining dextromethorphan's teratogenic potential.
- Further research is needed to elucidate the role of metabolic enzyme expression in these observed toxicities.
