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Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function.

Watson CY, Molina RM, Louzada A, Murdaugh KM, Donaghey TC, Brain JD - Int J Nanomedicine (2015)

Bottom Line: We found that the liver was the major site of initial uptake of (65)ZnO ENPs.In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility.Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys.

View Article: PubMed Central - PubMed

Affiliation: Center for Nanotechnology and Nanotoxicology, Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

ABSTRACT

Background: Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration.

Materials and methods: First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated (65)ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa. Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively.

Results: We found that the liver was the major site of initial uptake of (65)ZnO ENPs. There was a time-dependent decrease in tissue levels of (65)Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P. aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver.

Conclusion: Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury.

No MeSH data available.


Related in: MedlinePlus

Magnetometric evaluations of Kupffer cells.Notes: At (A) 30 minutes, (B) 24 hours, and (C) 7 days postinjection of ZnO engineered nanoparticles. rats were intravenously injected with 5 mg/kg each of ZnO engineered nanoparticles and Fe2O3 tracer nanoparticles. At each time point, magnetometric measurements were collected for 30 minutes. Significant slowing in relaxation was observed at 30 minutes and 24 hours compared to control animals (Fe2O3 only; student’s t-test was used to evaluate the B30/B0). At 7 days, relaxation returned to normal when there was a 25% reduction in 65Zn retained in the liver (n=6, P<0.01).Abbreviation: B0, initial magnetic field strength.
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f3-ijn-10-4173: Magnetometric evaluations of Kupffer cells.Notes: At (A) 30 minutes, (B) 24 hours, and (C) 7 days postinjection of ZnO engineered nanoparticles. rats were intravenously injected with 5 mg/kg each of ZnO engineered nanoparticles and Fe2O3 tracer nanoparticles. At each time point, magnetometric measurements were collected for 30 minutes. Significant slowing in relaxation was observed at 30 minutes and 24 hours compared to control animals (Fe2O3 only; student’s t-test was used to evaluate the B30/B0). At 7 days, relaxation returned to normal when there was a 25% reduction in 65Zn retained in the liver (n=6, P<0.01).Abbreviation: B0, initial magnetic field strength.

Mentions: In vivo magnetometry was employed to assess the impact of ENP exposure on the phagosomal motility of liver macrophages or Kupffer cells. Magnetometric analyses were performed at three time points: 30 minutes, 24 hours, and 7 days. As shown in Figure 3A, 30 minutes after injecting ZnO ENPs, significant slowing in relaxation was observed compared with control (Fe2O3 only). The slowed relaxation persisted at 24 hours (Figure 3B). However, the motility of particle-containing phagosomes in Kupffer cells returned to the control level at 7 days (Figure 3C).


Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function.

Watson CY, Molina RM, Louzada A, Murdaugh KM, Donaghey TC, Brain JD - Int J Nanomedicine (2015)

Magnetometric evaluations of Kupffer cells.Notes: At (A) 30 minutes, (B) 24 hours, and (C) 7 days postinjection of ZnO engineered nanoparticles. rats were intravenously injected with 5 mg/kg each of ZnO engineered nanoparticles and Fe2O3 tracer nanoparticles. At each time point, magnetometric measurements were collected for 30 minutes. Significant slowing in relaxation was observed at 30 minutes and 24 hours compared to control animals (Fe2O3 only; student’s t-test was used to evaluate the B30/B0). At 7 days, relaxation returned to normal when there was a 25% reduction in 65Zn retained in the liver (n=6, P<0.01).Abbreviation: B0, initial magnetic field strength.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492628&req=5

f3-ijn-10-4173: Magnetometric evaluations of Kupffer cells.Notes: At (A) 30 minutes, (B) 24 hours, and (C) 7 days postinjection of ZnO engineered nanoparticles. rats were intravenously injected with 5 mg/kg each of ZnO engineered nanoparticles and Fe2O3 tracer nanoparticles. At each time point, magnetometric measurements were collected for 30 minutes. Significant slowing in relaxation was observed at 30 minutes and 24 hours compared to control animals (Fe2O3 only; student’s t-test was used to evaluate the B30/B0). At 7 days, relaxation returned to normal when there was a 25% reduction in 65Zn retained in the liver (n=6, P<0.01).Abbreviation: B0, initial magnetic field strength.
Mentions: In vivo magnetometry was employed to assess the impact of ENP exposure on the phagosomal motility of liver macrophages or Kupffer cells. Magnetometric analyses were performed at three time points: 30 minutes, 24 hours, and 7 days. As shown in Figure 3A, 30 minutes after injecting ZnO ENPs, significant slowing in relaxation was observed compared with control (Fe2O3 only). The slowed relaxation persisted at 24 hours (Figure 3B). However, the motility of particle-containing phagosomes in Kupffer cells returned to the control level at 7 days (Figure 3C).

Bottom Line: We found that the liver was the major site of initial uptake of (65)ZnO ENPs.In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility.Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys.

View Article: PubMed Central - PubMed

Affiliation: Center for Nanotechnology and Nanotoxicology, Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

ABSTRACT

Background: Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration.

Materials and methods: First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated (65)ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa. Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively.

Results: We found that the liver was the major site of initial uptake of (65)ZnO ENPs. There was a time-dependent decrease in tissue levels of (65)Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P. aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver.

Conclusion: Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury.

No MeSH data available.


Related in: MedlinePlus