In vitro blood–brain barrier model adapted to repeated-dose toxicological screening
| Autor: | C. Landry, R. Aijjou, Maxime Culot, R. Cecchelli, A. Fabulas-da Costa, Johan Hachani |
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| Přispěvatelé: | Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Drug-Related Side Effects and Adverse Reactions
Endothelial cells [SDV]Life Sciences [q-bio] Central nervous system Drug Evaluation Preclinical Pharmacology Biology Toxicology Blood–brain barrier Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Chronic toxicity Cyclosporin a Toxicity Tests medicine Animals Colchicine Restrictive Barrier Cells Cultured 030304 developmental biology 0303 health sciences General Medicine In vitro model Coculture Techniques Rats 3. Good health medicine.anatomical_structure Animals Newborn chemistry Blood-Brain Barrier Nanoparticles for drug delivery to the brain Toxicity cardiovascular system Cattle Neuroglia 030217 neurology & neurosurgery |
| Zdroj: | Toxicology in Vitro Toxicology in Vitro, Elsevier, 2013, 27 (6), pp.1944-1953. ⟨10.1016/j.tiv.2013.06.026⟩ Toxicology in Vitro; Vol 27 |
| ISSN: | 0887-2333 |
| Popis: | International audience; Toxicity to the central nervous system (CNS) is a key feature in the toxicological profile of compounds and there is a growing interest to use in vitro cell assays. The blood-brain barrier (BBB) is a highly restrictive barrier that preserves homeostasis within the brain microenvironment. By modelling the BBB it is possible to investigate whether a compound is likely to compromise its functionality, which would cause unwanted effects on brain cells. These investigations are usually performed using a single exposure to drugs, whereas CNS side effects usually result from repeated exposures. The main objective of this study was to adapt our established BBB model to the evaluation of repeated-dose toxicity at the BBB. Studies were undertaken within the European Predict-IV consortium to study the effect on BBB permeability of 12 selected drugs after 14 days of repeated treatment to a single pre-selected concentration. Compared to single exposure, a 100-fold lower colchicine concentration in 14 days repeated-dose treatment was toxic. This demonstrates the importance to evaluate the BBB toxicity in repeated-dose testing. Finally, the potentiating effects of cyclosporin A on the BBB toxicity of colchicine illustrate the possibility to use in vitro BBB models to make risk assessment of drug-drug |
| Databáze: | OpenAIRE |
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