The in vitro biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure.

Détails

ID Serval
serval:BIB_1CD7D37A6F02
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The in vitro biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure.
Périodique
Toxicology In Vitro
Auteur(s)
Broeders J.J., Hermens J.L., Blaauboer B.J., Zurich M.G.
ISSN
1879-3177 (Electronic)
ISSN-L
0887-2333
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
30
Numéro
1 Pt A
Pages
185-191
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Neurotoxic effects of compounds can be tested in vitro using cell systems. One example is aggregating rat brain cell cultures. For the extrapolation of in vitro data to the in vivo situation, it is important to take the biokinetics of the test compound into account. In addition, the exposure in vivo is often for a longer period of time; therefore, it is crucial to incorporate this into in vitro assays as well. In this study, aggregating rat brain cell cultures were exposed to chlorpromazine (CPZ) and diazepam (DZP) for 12-days with repeated exposure. Samples were taken from the stocks, test media, cell culture media and cells at specific time points on the first and last exposure day. These samples were analysed by HPLC-UV. The amount of CPZ in the medium decreased over time, whereas the amount in the cells showed an increase. Accumulation of CPZ in the cells was seen over the 12-day repeated exposure. The amount of DZP in the medium remained stable over time and only up to 2% of DZP added was found in the cells. Different biokinetic behaviour was found for CPZ and DZP. Possible explanations are differences in uptake into the cells or efflux out of the cells. The decrease of CPZ in the medium versus the stable amount of DZP results in differences in exposure concentrations over time, which should be taken into account when interpreting in vitro effect data.
Mots-clé
Animals, Brain/cytology, Cells, Cultured, Chlorpromazine/administration & dosage, Chlorpromazine/pharmacokinetics, Diazepam/administration & dosage, Diazepam/pharmacokinetics, Dopamine Antagonists/administration & dosage, Dopamine Antagonists/pharmacokinetics, GABA Modulators/administration & dosage, GABA Modulators/pharmacokinetics, Neurons/metabolism, Rats
Pubmed
Web of science
Création de la notice
02/02/2016 18:48
Dernière modification de la notice
20/08/2019 13:53
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