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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

Effect of ZnO ENPs on the fate of IV-injected Pseudomonas aeruginosa.Notes: (A) Bacterial clearance of Pseudomonas aeruginosa in the blood and tissues. Bacteria were rapidly cleared from the blood. Rats pretreated with ZnO engineered nanoparticles with or without Fe2O3 showed slightly slower clearance for the first 30 minutes, but by 60 minutes there were almost no viable bacteria detected in the blood. (B) At 10 minutes postinjection of bacteria, the majority of the injected dose was found in the liver, spleen, and blood. (C) At 4 hours, very low levels of viable bacteria remained in these organs. (D) Bacterial inactivation in 4 hours. Compared to 10 minutes, viable bacteria (cfu/g) in the liver, lungs, and kidneys were significantly decreased. However, pretreatment of rats with ZnO engineered nanoparticles with or without Fe2O3 did not affect bacterial killing in these organs.Abbreviations: ENPs, engineered nanoparticles; IV, intravenous.
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f4-ijn-10-4173: Effect of ZnO ENPs on the fate of IV-injected Pseudomonas aeruginosa.Notes: (A) Bacterial clearance of Pseudomonas aeruginosa in the blood and tissues. Bacteria were rapidly cleared from the blood. Rats pretreated with ZnO engineered nanoparticles with or without Fe2O3 showed slightly slower clearance for the first 30 minutes, but by 60 minutes there were almost no viable bacteria detected in the blood. (B) At 10 minutes postinjection of bacteria, the majority of the injected dose was found in the liver, spleen, and blood. (C) At 4 hours, very low levels of viable bacteria remained in these organs. (D) Bacterial inactivation in 4 hours. Compared to 10 minutes, viable bacteria (cfu/g) in the liver, lungs, and kidneys were significantly decreased. However, pretreatment of rats with ZnO engineered nanoparticles with or without Fe2O3 did not affect bacterial killing in these organs.Abbreviations: ENPs, engineered nanoparticles; IV, intravenous.

Mentions: As shown in Figure 4A, there had been rapid clearance of bacteria from the blood at 1 hour postinjection. Although there were initially higher levels of bacteria remaining in the blood of the ZnO and ZnO/Fe2O3 groups, viable bacteria were almost completely cleared from the blood in the first hour in all three groups. The percentages of viable bacteria recovered in the liver, spleen, lungs, kidneys, and blood at 10 minutes postinjection are shown in Figure 4B. After 4 hours, the viable bacteria remaining in the liver, spleen, lungs, kidneys, and blood were significantly reduced, as shown in Figure 4C. A summary of the percentage bacterial killing within each tissue is presented in Figure 4D. The graph indicates that bacteria in the lungs and kidneys were inactivated by almost 100% over a 4-hour period. Bacterial killing in the liver and spleen was over 92%.


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)

Effect of ZnO ENPs on the fate of IV-injected Pseudomonas aeruginosa.Notes: (A) Bacterial clearance of Pseudomonas aeruginosa in the blood and tissues. Bacteria were rapidly cleared from the blood. Rats pretreated with ZnO engineered nanoparticles with or without Fe2O3 showed slightly slower clearance for the first 30 minutes, but by 60 minutes there were almost no viable bacteria detected in the blood. (B) At 10 minutes postinjection of bacteria, the majority of the injected dose was found in the liver, spleen, and blood. (C) At 4 hours, very low levels of viable bacteria remained in these organs. (D) Bacterial inactivation in 4 hours. Compared to 10 minutes, viable bacteria (cfu/g) in the liver, lungs, and kidneys were significantly decreased. However, pretreatment of rats with ZnO engineered nanoparticles with or without Fe2O3 did not affect bacterial killing in these organs.Abbreviations: ENPs, engineered nanoparticles; IV, intravenous.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-10-4173: Effect of ZnO ENPs on the fate of IV-injected Pseudomonas aeruginosa.Notes: (A) Bacterial clearance of Pseudomonas aeruginosa in the blood and tissues. Bacteria were rapidly cleared from the blood. Rats pretreated with ZnO engineered nanoparticles with or without Fe2O3 showed slightly slower clearance for the first 30 minutes, but by 60 minutes there were almost no viable bacteria detected in the blood. (B) At 10 minutes postinjection of bacteria, the majority of the injected dose was found in the liver, spleen, and blood. (C) At 4 hours, very low levels of viable bacteria remained in these organs. (D) Bacterial inactivation in 4 hours. Compared to 10 minutes, viable bacteria (cfu/g) in the liver, lungs, and kidneys were significantly decreased. However, pretreatment of rats with ZnO engineered nanoparticles with or without Fe2O3 did not affect bacterial killing in these organs.Abbreviations: ENPs, engineered nanoparticles; IV, intravenous.
Mentions: As shown in Figure 4A, there had been rapid clearance of bacteria from the blood at 1 hour postinjection. Although there were initially higher levels of bacteria remaining in the blood of the ZnO and ZnO/Fe2O3 groups, viable bacteria were almost completely cleared from the blood in the first hour in all three groups. The percentages of viable bacteria recovered in the liver, spleen, lungs, kidneys, and blood at 10 minutes postinjection are shown in Figure 4B. After 4 hours, the viable bacteria remaining in the liver, spleen, lungs, kidneys, and blood were significantly reduced, as shown in Figure 4C. A summary of the percentage bacterial killing within each tissue is presented in Figure 4D. The graph indicates that bacteria in the lungs and kidneys were inactivated by almost 100% over a 4-hour period. Bacterial killing in the liver and spleen was over 92%.

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