Article

TLR4 Signaling Is Involved in Brain Vascular Toxicity of PCB153 Bound to Nanoparticles

Virginia Commonwealth University, United States of America
PLoS ONE (Impact Factor: 3.23). 05/2013; 8(5):e63159. DOI: 10.1371/journal.pone.0063159
Source: PubMed

ABSTRACT

PCBs bind to environmental particles; however, potential toxicity exhibited by such complexes is not well understood. The aim of the present study is to study the hypothesis that assembling onto nanoparticles can influence the PCB153-induced brain endothelial toxicity via interaction with the toll-like receptor 4 (TLR4). To address this hypothesis, TLR4-deficient and wild type control mice (males, 10 week old) were exposed to PCB153 (5 ng/g body weight) bound to chemically inert silica nanoparticles (PCB153-NPs), PCB153 alone, silica nanoparticles (NPs; diameter, 20 nm), or vehicle. Selected animals were also subjected to 40 min ischemia, followed by a 24 h reperfusion. As compared to exposure to PCB153 alone, treatment with PCB153-NP potentiated the brain infarct volume in control mice. Importantly, this effect was attenuated in TLR4-deficient mice. Similarly, PCB153-NP-induced proinflammatory responses and disruption of tight junction integrity were less pronounced in TLR4-deficient mice as compared to control animals. Additional in vitro experiments revealed that TLR4 mediates toxicity of PCB153-NP via recruitment of tumor necrosis factor-associated factor 6 (TRAF6). The results of current study indicate that binding to seemingly inert nanoparticles increase cerebrovascular toxicity of PCBs and suggest that targeting the TLR4/TRAF6 signaling may protect against these effects.

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Available from: Sung Yong Eum, Jun 29, 2015
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    • "Toxicity of these administered nanoparticles for imaging and loading drug (as a carrier) should also be considered. The polysorbate 80-coated PBCA (poly n-butylcyanoacrylate) particles and PEGylated PLAimmune nanoparticles can cross the BBB, but cause severe side effects which can affect the brain physiology and BBB function (Zhang et al. 2013). Additionally , nanoparticles possess physical and chemical characteristics that may cause oxidative stress (Batrakova et al. 2007). "

    Full-text · Dataset · Jul 2015
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    • "Toxicity of these administered nanoparticles for imaging and loading drug (as a carrier) should also be considered. The polysorbate 80-coated PBCA (poly n-butylcyanoacrylate) particles and PEGylated PLAimmune nanoparticles can cross the BBB, but cause severe side effects which can affect the brain physiology and BBB function (Zhang et al. 2013). Additionally , nanoparticles possess physical and chemical characteristics that may cause oxidative stress (Batrakova et al. 2007). "

    Full-text · Dataset · Jul 2015
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