PUBLICATION
Zebrafish embryotoxicity test for developmental (neuro) toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs
- Authors
- van Woudenberg, A.B., Snel, C., Rijkmans, E., de Groot, D., Bouma, M., Hermsen, S., Piersma, A., Menke, A., Wolterbeek, A.
- ID
- ZDB-PUB-140812-1
- Date
- 2014
- Source
- Reproductive toxicology (Elmsford, N.Y.) 49: 101-16 (Journal)
- Registered Authors
- Keywords
- Antiepileptic drugs, Behavior, Developmental (neuro) toxicity, Gene expression, Histopathology, Integrated test strategy, Kinetics, Zebrafish embryotoxicity test (ZET)
- MeSH Terms
-
- Animals
- Anticonvulsants/toxicity*
- Brain/drug effects
- Brain/embryology
- Carbamazepine/toxicity
- Dose-Response Relationship, Drug
- Endpoint Determination
- Ethosuximide/toxicity
- In Situ Hybridization
- Piracetam/analogs & derivatives
- Piracetam/toxicity
- Toxicity Tests/methods
- Valproic Acid/toxicity
- Zebrafish/embryology*
- PubMed
- 25111975 Full text @ Reprod. Toxicol.
- CTD
- 25111975
Citation
van Woudenberg, A.B., Snel, C., Rijkmans, E., de Groot, D., Bouma, M., Hermsen, S., Piersma, A., Menke, A., Wolterbeek, A. (2014) Zebrafish embryotoxicity test for developmental (neuro) toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs. Reproductive toxicology (Elmsford, N.Y.). 49:101-16.
Abstract
To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro) toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60μM. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180μM. For ETH, all endpoints showed similar sensitivity (6.6mM), whereas MA was the most sensitive parameter for LEV (40mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping