Effects of Lead and Cadmium on Brain Endothelial Cell Survival, Monolayer Permeability, and Crucial Oxidative Stress Markers in an in Vitro Model of the Blood-Brain Barrier
| Autor: | Hsiu-Jen Wang, Joshua W. Carey, Nuran Ercal, William A. Banks, Shakila Tobwala |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
cadmium
Health Toxicology and Mutagenesis blood brain barrier Toxicology Blood–brain barrier medicine.disease_cause lcsh:Chemical technology reactive oxygen species neurotoxicty lead chemistry.chemical_compound medicine lcsh:TP1-1185 Viability assay chemistry.chemical_classification Reactive oxygen species Chemical Health and Safety biology Neurotoxicity Glutathione medicine.disease Cell biology Endothelial stem cell medicine.anatomical_structure chemistry Biochemistry Catalase biology.protein Oxidative stress |
| Zdroj: | Toxics, Vol 2, Iss 2, Pp 258-275 (2014) Toxics; Volume 2; Issue 2; Pages: 258-275 |
| ISSN: | 2305-6304 |
| Popis: | Oxidative stress, which is the loss of balance between antioxidant defense and oxidant production in the cells, is implicated in the molecular mechanism of heavy metal-induced neurotoxicity. Given the key role of lead (Pb) and cadmium (Cd) in inducing oxidative stress, we investigated their role in disrupting the integrity and function of immortalized human brain microvascular endothelial cells (hCMEC/D3). To study this, hCMEC/D3 cells were exposed to control media or to media containing different concentrations of Pb or Cd. Those exposed to Pb or Cd showed significantly higher oxidative stress than the untreated group, as indicated by cell viability, reactive oxygen species (ROS), glutathione (GSH) levels, and catalase enzyme activity. Pb also induced oxidative stress-related disruption of the hCMEC/D3 cell monolayer, as measured by trans-endothelial electrical resistance (TEER), the dextran permeability assay, and the level of tight junction protein, zona occluden protein (ZO-2). However, no significant disruption in the integrity of the endothelial monolayer was seen with cadmium at the concentrations used. Taken together, these results show that Pb and Cd induce cell death and dysfunction in hCMEC/D3 cells and, in the case of Pb, barrier disruption. This suggests blood brain barrier (BBB) dysfunction as a contributing mechanism in Pb and Cd neurotoxicities. |
| Databáze: | OpenAIRE |
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