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Toxicol In Vitro ; 23(3): 447-53, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19135142

RESUMO

The combination of an in vitro BBB model (4d/24w) with a neuronal cell line (SH-SY5Y) provides a convenient approach to explore the importance of BBB permeability in neurotoxicity assessment of compounds. The toxicity of 16 compounds on SH-SY5Y cells was evaluated after 24h incubation with each compound and compared to their toxicity on SH-SY5Y after passage through the BBB model. Nine out of 16 compounds were found toxic after direct exposure at 100muM while only three still induced toxicity on SH-SY5Y cells after BBB transport. The BBB permeability values of each compound revealed that in the case of compounds that did not induce toxicity, the amount that crossed the BBB was not enough to exert a toxic effect on the neuronal cells. Since disrupting the BBB may also cause unwanted effect on brain cells, the BBB toxicity of these compounds have been assessed. Our results prompted the importance of BBB permeability assessment in neurotoxicity evaluation, as it allows a better estimation of the actual concentration at the target site.


Assuntos
Alternativas aos Testes com Animais , Barreira Hematoencefálica/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Xenobióticos/toxicidade , Animais , Barreira Hematoencefálica/metabolismo , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Sistema Nervoso/metabolismo , Neuroblastoma , Neurônios/metabolismo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo , Xenobióticos/classificação , Xenobióticos/metabolismo
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