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New strategy for alerting central nervous system toxicity: Integration of blood-brain barrier toxicity and permeability in neurotoxicity assessment
- Source :
- Toxicology in Vitro, Toxicology in Vitro, Elsevier, 2009, 23, p. 447-453, HAL
- Publication Year :
- 2009
- Publisher :
- HAL CCSD, 2009.
-
Abstract
- International audience; 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 24 h 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 100 μM 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.
- Subjects :
- Cell Membrane Permeability
Cell Survival
Central nervous system
Tetrazolium Salts
Pharmacology
Biology
Animal Testing Alternatives
Toxicology
Blood–brain barrier
Nervous System
Xenobiotics
Neuroblastoma
03 medical and health sciences
0302 clinical medicine
In vitro model
Predictive Value of Tests
Cell Line, Tumor
medicine
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
030304 developmental biology
Blood-brain barrier
Neurons
0303 health sciences
Neurotoxicity
Reproducibility of Results
Neurotoxicity assessment
General Medicine
medicine.disease
In vitro
3. Good health
Thiazoles
medicine.anatomical_structure
Target site
nervous system
Cell culture
Permeability (electromagnetism)
Toxicity
cardiovascular system
Cattle
Testing strategy
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 08872333
- Database :
- OpenAIRE
- Journal :
- Toxicology in Vitro, Toxicology in Vitro, Elsevier, 2009, 23, p. 447-453, HAL
- Accession number :
- edsair.doi.dedup.....389578a2164c7f23a740aaa2859a46f7