Brain Accumulation and Toxicity Profiles of Silica Nanoparticles: The Influence of Size and Exposure Route.

Nanoparticles (NPs) can make their way to the brain and cause in situ damage, which is a concern for nanomaterial application and airborne particulate matter exposure. Our recent study indicated that respiratory exposure to silica nanoparticles (SiO2 NPs) caused unexpected cardiovascular toxic effects. However, the toxicities of SiO2 NPs in other organs have warranted further investigation. To confirm the accumulation of SiO2 NPs in the brain, we introduced SiO2 NPs with different diameters into mice via intranasal instillation (INI) and intravenous injection (IVI) in parallel. We found that SiO2 NPs may target the brain through both olfactory and systemic routes, but the size of SiO2 NPs and delivery routes both significantly affected their brain accumulation. Surprisingly, while equivalent SiO2 NPs were found in the brain regions, brain lesions were distinctly much higher in INI than in the IVI group. Mechanistically, we showed that SiO2 NPs introduced via INI induced brain apoptosis and autophagy, while the SiO2 NPs introduced via IVI only induced autophagy in the brain.

Polychlorinated Biphenyl Quinone Metabolites Cause Neutrophil Extracellular Traps in Mouse Bone Marrow Neutrophils.

Polychlorinated biphenyls (PCBs) are a group of persistent organic environmental pollutants with various toxic effects. Our previous research found that a highly reactive quinone metabolite of PCBs, namely, PCB29-pQ, causes excessive reactive oxygen species (ROS) production and different toxic actions. Neutrophil extracellular traps (NETs), the product of NETosis, are one of the newly discovered programmed cell deaths. Recent studies have suggested the association of NET formation with excess ROS. The objective of this study was to investigate the influence of PCB29-pQ exposure on NETs and its possible molecular mechanisms. Using scanning electron microscopy, immunofluorescence microscopy, and the quantitative analysis of extracellular DNA, we found that PCB29-pQ exposure induces the formation of NETs in mouse bone marrow. Mechanistically, our results suggested that PCB29-pQ induces histone citrullination and chromatin decondensation, which are necessary processes for NET formation. Moreover, PCB29-pQ exposure increases ROS and autophagy levels, while ROS and autophagy inhibitors significantly reverse NET formation. These results indicated that PCB29-pQ-induced NET formation was mediated by the intracellular ROS level and autophagy signaling. In general, our research uncovered a toxicity mechanism of PCB29-pQ, which suggested the necessity of evaluating its immunotoxicity during the risk assessment of PCB exposure.