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

Christa Y Watson, Ramon M Molina, Andressa Louzada, Kimberly M Murdaugh, Thomas C Donaghey, Joseph D BrainCenter for Nanotechnology and Nanotoxicology, Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public H...

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Autores principales:	Watson CY, Molina RM, Louzada A, Murdaugh KM, Donaghey TC, Brain JD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5285e731123046d6a66a17a0358e891c
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spelling	oai:doaj.org-article:5285e731123046d6a66a17a0358e891c2021-12-02T02:45:55ZEffects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function1178-2013https://doaj.org/article/5285e731123046d6a66a17a0358e891c2015-06-01T00:00:00Zhttp://www.dovepress.com/effects-of-zinc-oxide-nanoparticles-on-kupffer-cell-phagosomal-motilit-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Christa Y Watson, Ramon M Molina, Andressa Louzada, Kimberly M Murdaugh, Thomas C Donaghey, Joseph D BrainCenter for Nanotechnology and Nanotoxicology, Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USABackground: 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 65ZnO 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 65ZnO ENPs. There was a time-dependent decrease in tissue levels of 65Zn in all organs examined, reflecting 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.Keywords: magnetometry, engineered nanoparticles, liver, Kupffer cells, zinc oxideWatson CYMolina RMLouzada AMurdaugh KMDonaghey TCBrain JDDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 4173-4184 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Watson CY Molina RM Louzada A Murdaugh KM Donaghey TC Brain JD Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function
description	Christa Y Watson, Ramon M Molina, Andressa Louzada, Kimberly M Murdaugh, Thomas C Donaghey, Joseph D BrainCenter for Nanotechnology and Nanotoxicology, Molecular and Integrative Physiological Sciences Program, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USABackground: 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 65ZnO 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 65ZnO ENPs. There was a time-dependent decrease in tissue levels of 65Zn in all organs examined, reflecting 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.Keywords: magnetometry, engineered nanoparticles, liver, Kupffer cells, zinc oxide
format	article
author	Watson CY Molina RM Louzada A Murdaugh KM Donaghey TC Brain JD
author_facet	Watson CY Molina RM Louzada A Murdaugh KM Donaghey TC Brain JD
author_sort	Watson CY
title	Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function
title_short	Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function
title_full	Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function
title_fullStr	Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function
title_full_unstemmed	Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function
title_sort	effects of zinc oxide nanoparticles on kupffer cell phagosomal motility, bacterial clearance, and liver function
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/5285e731123046d6a66a17a0358e891c
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Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

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