"Green" Synthesized and Coated Nanosilver Alters the Membrane Permeability of Barrier (Intestinal, Brain Endothelial) Cells and Stimulates Oxidative Stress Pathways in Neurons

Nanosilvers (nanoAg) use in medical applications and consumer products is increasing. Because of this, its green synthesis and surface modification with beneficial coatings are desirable. Given nanoAgs potential exposure routes (e.g., dermal, intestinal, pulmonary), questions on its potential to move through these port of entry barriers and enter the bodys circulatory system remain unanswered. In view of nanoAgs free radical activity and the brains sensitivity to oxidative stress damage, the possibility that nanoAg particles can move from the systemic circulation, transport through the blood-brain barrier (BBB), and pose a neurotoxic threat is also a legitimate concern. Because of these issues, this study addresses an initial event of barrier transport, that is, if "green" synthesized nanoAg, coated with green tea polyphenols (GT) or glutathione (GSH), can alter the permeability of human intestinal epithelial (Caco-2) or rat brain endothelial (RBEC4) barrier cells. Additionally, it asks if such green synthesized nanoAg modifies its toxicity to oxidative stress-sensitive cultured neurons (N27). Physicochemical (PC) characterization of conventionally synthesized nanoAg and green synthesized nanoAg-GT or nanoAg-GSH indicated that all samples aggregated (>5002500 nm) when suspended in cell culture exposure media. NanoAg-GSH showed the least electronegative zeta potential and largest aggregate size in both Caco-2 and RBEC4 exposure media, relative to conventional nanoAg. Transcellular resistance measures indicated that within 15 min of exposure to 6.5 ppm, both conventional and nanoAg-GSH altered the permeability of intestinal Caco-2 monolayers, and all nanoAg treatments altered the permeability of RBEC4 brain endothelial cells. To examine if a differential toxicity existed in the response of oxidative stress-sensitive neurons, a noncytotoxic (1.0 ppm) concentration of each nanoAg material was exposed (18 h) to rat dopaminergic neurons (N27), transfected with a NF kappa beta reporter gene. Results indicated that all nanoAg samples significantly stimulated this oxidative stress pathway in the N27 neuron. Together, these data suggest that both conventional and green synthesized coated nanoAg alter the permeability of barrier cell membranes and activate oxidative stress pathways in target neurons, equivocally.