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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

Detection of the neuron-specific protein NeuN on rat left hemispheres.Notes: Cerebellum regions of tested rats are pictured and organized according to zinc oxide (ZnO) character (particle sizes [20 and 100 nm], positively and negatively charged surfaces, and injected concentrations), as indicated by black bars. (A) Phosphate-buffered saline-injected control normal rat brain of cerebellum region; (B) 10 mg of ZnOSM20(+); (C) 0.1 mg of ZnOSM20(+); (D) 10 mg of ZnOSM20(−); (E) 0.1 mg of ZnOSM20(−); (F) 10 mg of ZnOSM100(+); (G) 0.1 mg of ZnOSM100(+); (H) 10 mg of ZnOSM100(−); (I) 0.1 mg of ZnOSM100(−).
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f4-ijn-9-225: Detection of the neuron-specific protein NeuN on rat left hemispheres.Notes: Cerebellum regions of tested rats are pictured and organized according to zinc oxide (ZnO) character (particle sizes [20 and 100 nm], positively and negatively charged surfaces, and injected concentrations), as indicated by black bars. (A) Phosphate-buffered saline-injected control normal rat brain of cerebellum region; (B) 10 mg of ZnOSM20(+); (C) 0.1 mg of ZnOSM20(+); (D) 10 mg of ZnOSM20(−); (E) 0.1 mg of ZnOSM20(−); (F) 10 mg of ZnOSM100(+); (G) 0.1 mg of ZnOSM100(+); (H) 10 mg of ZnOSM100(−); (I) 0.1 mg of ZnOSM100(−).

Mentions: The brains of animals were investigated by IHC method with NeuN-specific staining with Mayer’s hematoxylin counterstaining. In particular, cerebellums of the rats were examined for structural changes, and differences were compared to the normal control. Neuronal cells were stained specifically by using NeuN-specific antibody, and no morphological change was observed from ZnO NPs injected groups through animal’s tail vein in comparison to PBS-treated control group. No observable changes in brain slices were found in the rats treated with ZnO NPs of different sizes, surface charges, and concentrations (Figure 4).


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)

Detection of the neuron-specific protein NeuN on rat left hemispheres.Notes: Cerebellum regions of tested rats are pictured and organized according to zinc oxide (ZnO) character (particle sizes [20 and 100 nm], positively and negatively charged surfaces, and injected concentrations), as indicated by black bars. (A) Phosphate-buffered saline-injected control normal rat brain of cerebellum region; (B) 10 mg of ZnOSM20(+); (C) 0.1 mg of ZnOSM20(+); (D) 10 mg of ZnOSM20(−); (E) 0.1 mg of ZnOSM20(−); (F) 10 mg of ZnOSM100(+); (G) 0.1 mg of ZnOSM100(+); (H) 10 mg of ZnOSM100(−); (I) 0.1 mg of ZnOSM100(−).
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-9-225: Detection of the neuron-specific protein NeuN on rat left hemispheres.Notes: Cerebellum regions of tested rats are pictured and organized according to zinc oxide (ZnO) character (particle sizes [20 and 100 nm], positively and negatively charged surfaces, and injected concentrations), as indicated by black bars. (A) Phosphate-buffered saline-injected control normal rat brain of cerebellum region; (B) 10 mg of ZnOSM20(+); (C) 0.1 mg of ZnOSM20(+); (D) 10 mg of ZnOSM20(−); (E) 0.1 mg of ZnOSM20(−); (F) 10 mg of ZnOSM100(+); (G) 0.1 mg of ZnOSM100(+); (H) 10 mg of ZnOSM100(−); (I) 0.1 mg of ZnOSM100(−).
Mentions: The brains of animals were investigated by IHC method with NeuN-specific staining with Mayer’s hematoxylin counterstaining. In particular, cerebellums of the rats were examined for structural changes, and differences were compared to the normal control. Neuronal cells were stained specifically by using NeuN-specific antibody, and no morphological change was observed from ZnO NPs injected groups through animal’s tail vein in comparison to PBS-treated control group. No observable changes in brain slices were found in the rats treated with ZnO NPs of different sizes, surface charges, and concentrations (Figure 4).

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