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Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos
Published on: August 25, 2019
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Mycophenolic Acid-Induced Developmental Defects in Zebrafish Embryos
Ling-Ling Jiang1, Mei-Hui Liu2, Jian-Ying Li3
1Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, People's Republic of China.
International Journal of Toxicology
|October 4, 2016
Summary
Mycophenolic acid (MPA) causes birth defects in zebrafish embryos by inhibiting purine synthesis. Adding guanosine partially reversed these toxic effects, suggesting a mechanism involving nucleotide depletion.
Area of Science:
- Developmental toxicology
- Pharmacology
- Molecular biology
Background:
- Mycophenolic acid (MPA) is increasingly used in organ transplantation.
- Clinical studies suggest MPA is a human teratogen, but its mechanism is unclear.
- MPA inhibits de novo purine synthesis via inosine monophosphate dehydrogenase (IMPDH).
Purpose of the Study:
- To investigate the teratogenic effects of MPA on zebrafish embryos.
- To elucidate the mechanism underlying MPA-induced teratogenicity.
Main Methods:
- Zebrafish embryos were exposed to varying concentrations of MPA.
- Morphological defects were assessed.
- Quantitative polymerase chain reaction (qPCR) was used to analyze gene expression.
- Reversal studies with guanosine were performed.
Main Results:
- MPA caused dose-dependent morphological defects (tail curvature, pericardial edema) in zebrafish embryos.
- MPA significantly reduced impdh1b and impdh2 expression at the LC25 level.
- The teratogenic index was calculated as 16, confirming MPA's teratogenicity.
- Co-administration of guanosine partially reversed MPA-induced toxicity.
Conclusions:
- MPA is a teratogen in zebrafish embryos.
- MPA impairs embryonic development by inhibiting IMPDH activity.
- This inhibition leads to guanosine nucleotide depletion, causing developmental toxicity.
