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Assessment of ZnO and SiO2 nanoparticle permeability through and toxicity to the blood-brain barrier using Evans blue and TEM.

Shim KH, Jeong KH, Bae SO, Kang MO, Maeng EH, Choi CS, Kim YR, Hulme J, Lee EK, Kim MK, An SS - Int J Nanomedicine (2014)

Bottom Line: As increasing variants of nanoparticles (NPs) are being used in various products, it has become apparent that size alone can no longer adequately explain the variety of generated toxic profiles.Next, in order to assess whether ZnO NPs could compromise the BBB, ZnO NPs were intravenously injected on day 0, 7, 14, 21 and 28 no further treatment was administered for 62 days.These observations suggest that the BBB was not compromised and was able to block penetration of ZnO and SiO2 NPs, resulting in significant neurotoxic effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Republic of Korea.

ABSTRACT
As increasing variants of nanoparticles (NPs) are being used in various products, it has become apparent that size alone can no longer adequately explain the variety of generated toxic profiles. Recent studies with NPs have suggested that various sizes of NPs could determine in vitro toxicity. In an attempt to address concerns regarding neurotoxicity of zinc oxide (ZnO) and silica (SiO2) NPs, these were examined after exposing them via oral, dermal, and intravenous administrations of NPs and their toxicological effects on the brain over a prescribed period of time were assessed. After 28 days of repeated oral administrations of ZnO or SiO2 independently, possibly due to damages to the blood brain barrier (BBB), neurotoxicity, were investigated by Evans blue technique. Next, in order to assess whether ZnO NPs could compromise the BBB, ZnO NPs were intravenously injected on day 0, 7, 14, 21 and 28 no further treatment was administered for 62 days. Deposition of SiO2 in brain from repeated dermal and oral administrations for 90 days were evaluated by transmission electron microscopy coupled with scanning energy-dispersive X-ray spectroscopy. Physiochemical profiles were principally determined on particle size at the beginning of the current toxicity investigations on ZnO and SiO2 NPs. The BBB was found to be intact after independent repeated oral administrations of ZnO or SiO2 NPs for 28 days, suggesting no significant damage. Neuronal death was also not observed after the intravenous administrations of ZnO NPs. After 90 days of repeated dermal and oral administration of SiO2 NPs, no deposition of NPs was observed in hippocampus, striatum, and cerebellum regions using transmission electron microscope analyses. These observations suggest that the BBB was not compromised and was able to block penetration of ZnO and SiO2 NPs, resulting in significant neurotoxic effects. Moreover, absence of SiO2 in three regions of brain after dermal and oral administrations for 90 days suggested that brain was protected from SiO2. No behavior change was observed in all studies, suggesting that 90 days may not be long enough to assess full neurotoxicity of NPs in vivo.

No MeSH data available.


Related in: MedlinePlus

The results of energy-dispersive X-ray spectroscope analysis of SiO2EN20(–)-treated rat hippocampus via dermal administration.Notes: A and B are examples of suspected nano-size dot and graph of energy-dispersive X-ray spectroscope analysis.Abbreviations: Ca, calcium; Cl, chlorine; Cu, copper; Fe, iron; O, oxygen; OS, osmium; P, phosphorus; SiO2, silica; EDS, energy-dispersive X-ray spectroscope.
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f7-ijn-9-225: The results of energy-dispersive X-ray spectroscope analysis of SiO2EN20(–)-treated rat hippocampus via dermal administration.Notes: A and B are examples of suspected nano-size dot and graph of energy-dispersive X-ray spectroscope analysis.Abbreviations: Ca, calcium; Cl, chlorine; Cu, copper; Fe, iron; O, oxygen; OS, osmium; P, phosphorus; SiO2, silica; EDS, energy-dispersive X-ray spectroscope.

Mentions: Each group treated with SiO2 NPs was monitored for the presence of NPs in cerebellum, hippocampus, and striatum using TEM after dermal administration of SiO2EN20(−) and SiO2EN100(−) and oral administration of SiO2EN20(R) and SiO2EN100(R). After 90 days of repeated administrations, the brain was extracted and cut to 1 mm2 fragments and transported to the Korea Institute of Science and Technology (Seoul, Republic of Korea) for TEM analyses. Cerebellum, hippocampus, and striatum were investigated thoroughly, since the accumulation of NPs was expected to occur in those brain areas (Figure 6). Nano-size dots were observed in each brain region, and EDS analysis was performed to confirm the presence or absence of SiO2 NPs. According to EDS analysis, the Si peak was absent and only osmium and lead (dye materials) and carbon and Cu (grid materials) peaks were present, belonging to the pretreatment chemicals (Figure 7A). In addition, a suspected iron peak was observed, which could have been from the blood vessel in the brain (Figure 7B). In SiO2EN100(−) group, suspected nano-size dot was analyzed to conform silica NPs. However no silica peak appeared in the EDS graph (Figure 8).


Assessment of ZnO and SiO2 nanoparticle permeability through and toxicity to the blood-brain barrier using Evans blue and TEM.

Shim KH, Jeong KH, Bae SO, Kang MO, Maeng EH, Choi CS, Kim YR, Hulme J, Lee EK, Kim MK, An SS - Int J Nanomedicine (2014)

The results of energy-dispersive X-ray spectroscope analysis of SiO2EN20(–)-treated rat hippocampus via dermal administration.Notes: A and B are examples of suspected nano-size dot and graph of energy-dispersive X-ray spectroscope analysis.Abbreviations: Ca, calcium; Cl, chlorine; Cu, copper; Fe, iron; O, oxygen; OS, osmium; P, phosphorus; SiO2, silica; EDS, energy-dispersive X-ray spectroscope.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279764&req=5

f7-ijn-9-225: The results of energy-dispersive X-ray spectroscope analysis of SiO2EN20(–)-treated rat hippocampus via dermal administration.Notes: A and B are examples of suspected nano-size dot and graph of energy-dispersive X-ray spectroscope analysis.Abbreviations: Ca, calcium; Cl, chlorine; Cu, copper; Fe, iron; O, oxygen; OS, osmium; P, phosphorus; SiO2, silica; EDS, energy-dispersive X-ray spectroscope.
Mentions: Each group treated with SiO2 NPs was monitored for the presence of NPs in cerebellum, hippocampus, and striatum using TEM after dermal administration of SiO2EN20(−) and SiO2EN100(−) and oral administration of SiO2EN20(R) and SiO2EN100(R). After 90 days of repeated administrations, the brain was extracted and cut to 1 mm2 fragments and transported to the Korea Institute of Science and Technology (Seoul, Republic of Korea) for TEM analyses. Cerebellum, hippocampus, and striatum were investigated thoroughly, since the accumulation of NPs was expected to occur in those brain areas (Figure 6). Nano-size dots were observed in each brain region, and EDS analysis was performed to confirm the presence or absence of SiO2 NPs. According to EDS analysis, the Si peak was absent and only osmium and lead (dye materials) and carbon and Cu (grid materials) peaks were present, belonging to the pretreatment chemicals (Figure 7A). In addition, a suspected iron peak was observed, which could have been from the blood vessel in the brain (Figure 7B). In SiO2EN100(−) group, suspected nano-size dot was analyzed to conform silica NPs. However no silica peak appeared in the EDS graph (Figure 8).

Bottom Line: As increasing variants of nanoparticles (NPs) are being used in various products, it has become apparent that size alone can no longer adequately explain the variety of generated toxic profiles.Next, in order to assess whether ZnO NPs could compromise the BBB, ZnO NPs were intravenously injected on day 0, 7, 14, 21 and 28 no further treatment was administered for 62 days.These observations suggest that the BBB was not compromised and was able to block penetration of ZnO and SiO2 NPs, resulting in significant neurotoxic effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Bionano Technology, Gachon Medical Research Institute, Gachon University, Seongnam-si, Republic of Korea.

ABSTRACT
As increasing variants of nanoparticles (NPs) are being used in various products, it has become apparent that size alone can no longer adequately explain the variety of generated toxic profiles. Recent studies with NPs have suggested that various sizes of NPs could determine in vitro toxicity. In an attempt to address concerns regarding neurotoxicity of zinc oxide (ZnO) and silica (SiO2) NPs, these were examined after exposing them via oral, dermal, and intravenous administrations of NPs and their toxicological effects on the brain over a prescribed period of time were assessed. After 28 days of repeated oral administrations of ZnO or SiO2 independently, possibly due to damages to the blood brain barrier (BBB), neurotoxicity, were investigated by Evans blue technique. Next, in order to assess whether ZnO NPs could compromise the BBB, ZnO NPs were intravenously injected on day 0, 7, 14, 21 and 28 no further treatment was administered for 62 days. Deposition of SiO2 in brain from repeated dermal and oral administrations for 90 days were evaluated by transmission electron microscopy coupled with scanning energy-dispersive X-ray spectroscopy. Physiochemical profiles were principally determined on particle size at the beginning of the current toxicity investigations on ZnO and SiO2 NPs. The BBB was found to be intact after independent repeated oral administrations of ZnO or SiO2 NPs for 28 days, suggesting no significant damage. Neuronal death was also not observed after the intravenous administrations of ZnO NPs. After 90 days of repeated dermal and oral administration of SiO2 NPs, no deposition of NPs was observed in hippocampus, striatum, and cerebellum regions using transmission electron microscope analyses. These observations suggest that the BBB was not compromised and was able to block penetration of ZnO and SiO2 NPs, resulting in significant neurotoxic effects. Moreover, absence of SiO2 in three regions of brain after dermal and oral administrations for 90 days suggested that brain was protected from SiO2. No behavior change was observed in all studies, suggesting that 90 days may not be long enough to assess full neurotoxicity of NPs in vivo.

No MeSH data available.


Related in: MedlinePlus