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A Zebrafish Embryo Model to Screen Potential Therapeutic Compounds in Sapindaceae Poisoning.
Clovis P Wouters1, Benjamin Klein1, Nicholas Price2
1Department of Functional Sciences, Faculty of veterinary Medicine, Pharmacology and Toxicology, Fundamental and Applied Research for Animals & Health (FARAH), University of Liège, 4000 Liege, Belgium.
Molecules (Basel, Switzerland)
|October 26, 2024
Summary
A new zebrafish embryo model effectively screens for treatments against atypical myopathy (AM) caused by Sapindaceae plants. Glycine and carnitine showed promise in reducing mortality in this novel AM model.
Area of Science:
- Toxicology
- Animal Models
- Biochemistry
Background:
- Atypical myopathy (AM) in equids is caused by hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG) from Sapindaceae plants.
- These protoxins form toxic metabolites disrupting energy metabolism and causing rhabdomyolysis.
- Current treatment options are limited, and existing in vitro and mammalian models are insufficient for drug screening.
Purpose of the Study:
- To develop and validate a zebrafish embryo model for screening therapeutic compounds against AM.
- To assess the toxicity of HGA, MCPrG, and methylenecyclopropylacetate (MCPA) in zebrafish embryos.
- To identify potential biomarkers for HGA exposure.
Main Methods:
- Zebrafish embryos were exposed to HGA, MCPrG, and MCPA for 72 hours.
- Median lethal concentrations (LC50) were determined.
- Metabolite analysis (MCPA-carnitine, acylcarnitines) and biomarker assessment were performed.
- The efficacy of glycine, carnitine, and riboflavin as potential treatments was evaluated.
Main Results:
- HGA and MCPA induced toxicity with LC50 values of 1.7 µM and 1 µM, respectively; MCPrG was not toxic.
- Elevated MCPA-carnitine and altered acylcarnitine profiles were observed post-HGA exposure.
- Isovaleryl-/2-methylbutyrylcarnitine increases suggested potential biomarkers.
- Glycine and carnitine significantly reduced mortality, while riboflavin had no effect.
Conclusions:
- The zebrafish embryo model is a viable tool for identifying therapeutic agents for Sapindaceae poisoning.
- The model effectively replicates key toxicological and metabolic effects of HGA.
- Glycine and carnitine show therapeutic potential for treating AM.
