Cerebrovascular toxicity of PCB153 is enhanced by binding to silica nanoparticles.

Abstract

Environmental polychlorinated biphenyls (PCBs) are frequently bound onto nanoparticles (NPs). However, the toxicity and health effects of PCBs assembled onto nanoparticles are unknown. The aim of this study was to study the hypothesis that binding PCBs to silica NPs potentiates PCB-induced cerebrovascular toxicity and brain damage in an experimental stroke model. Mice (C57BL/6, males, 12-week-old) were exposed to PCB153 bound to NPs (PCB153-NPs), PCB153, or vehicle. PCB153 was administered in the amount of 5 ng/g body weight. A group of treated animals was subjected to a 40 min ischemia, followed by a 24 h reperfusion. The blood-brain barrier (BBB) permeability, brain infarct volume, expression of tight junction (TJ) proteins, and inflammatory mediators were assessed. As compared to controls, a 24 h exposure to PCB153-NPs injected into cerebral vasculature resulted in significant elevation of the BBB permeability, disruption of TJ protein expression, increased proinflammatory responses, and enhanced monocyte transmigration in mouse brain capillaries. Importantly, exposure to PCB153-NPs increased stroke volume and potentiated brain damage in mice subjected to ischemia/reperfusion. A long-term (30 days) oral exposure to PCB153-NPs resulted in a higher PCB153 content in the abdominal adipose tissue and amplified adhesion of leukocytes to the brain endothelium as compared to treatment with PCB153 alone. This study provides the first evidence that binding to NPs increases cerebrovascular toxicity of environmental toxicants, such as PCB153.

• Authors: Bei Zhang, Lei Chen, Jeong June Choi, Bernhard Hennig, Michal Toborek
• Journal: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology (J Neuroimmune Pharmacol) Vol. 7 Issue 4 Pg. 991-1001 (Dec 2012) ISSN: 1557-1904 [Electronic] United States
• PMID: 23081707 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Silicon Dioxide
• Polychlorinated Biphenyls
• 2,4,5,2',4',5'-hexachlorobiphenyl

Topics

• Adipose Tissue (metabolism)
• Animals
• Blood-Brain Barrier (metabolism)
• Capillaries (pathology)
• Carotid Artery, Internal
• Cell Movement
• Cerebrovascular Disorders (chemically induced, pathology)
• Dose-Response Relationship, Drug
• Endothelial Cells (metabolism)
• Gas Chromatography-Mass Spectrometry
• Immunohistochemistry
• Injections, Intra-Arterial
• Male
• Mice
• Mice, Inbred C57BL
• Nanoparticles
• Polychlorinated Biphenyls (administration & dosage, pharmacokinetics, toxicity)
• Real-Time Polymerase Chain Reaction
• Silicon Dioxide
• Stroke (chemically induced, pathology)
• Tight Junctions (metabolism)