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Toxics 2014, 2(2), 258-275; doi:10.3390/toxics2020258
Article

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

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Received: 2 April 2014; in revised form: 26 May 2014 / Accepted: 29 May 2014 / Published: 5 June 2014
(This article belongs to the collection Heavy Metals Toxicology)
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Abstract: 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.
Keywords: blood brain barrier; reactive oxygen species; neurotoxicty; lead; cadmium blood brain barrier; reactive oxygen species; neurotoxicty; lead; cadmium
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Tobwala, S.; Wang, H.-J.; Carey, J.W.; Banks, W.A.; Ercal, N. 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. Toxics 2014, 2, 258-275.

AMA Style

Tobwala S, Wang H-J, Carey JW, Banks WA, Ercal N. 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. Toxics. 2014; 2(2):258-275.

Chicago/Turabian Style

Tobwala, Shakila; Wang, Hsiu-Jen; Carey, Joshua W.; Banks, William A.; Ercal, Nuran. 2014. "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." Toxics 2, no. 2: 258-275.


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