Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs.

Autor: Beker van Woudenberg A; TNO, Research Group Risk Analysis for Products In Development (RAPID), Zeist, The Netherlands., Snel C; TNO Triskelion B.V., Zeist, The Netherlands., Rijkmans E; TNO, Research Group Risk Analysis for Products In Development (RAPID), Zeist, The Netherlands., de Groot D; TNO, Research Group Risk Analysis for Products In Development (RAPID), Zeist, The Netherlands., Bouma M; TNO, Research Group Risk Analysis for Products In Development (RAPID), Zeist, The Netherlands., Hermsen S; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands., Piersma A; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands., Menke A; TNO Triskelion B.V., Zeist, The Netherlands., Wolterbeek A; TNO, Research Group Risk Analysis for Products In Development (RAPID), Zeist, The Netherlands. Electronic address: andre.wolterbeek@tno.nl.
Jazyk: angličtina
Zdroj: Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2014 Nov; Vol. 49, pp. 101-16. Date of Electronic Publication: 2014 Aug 08.
DOI: 10.1016/j.reprotox.2014.07.082
Abstrakt: 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.
(Copyright © 2014 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: