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Title: Superparamagnetic iron oxide polyacrylic acid coated γ-Fe{sub 2}O{sub 3} nanoparticles do not affect kidney function but cause acute effect on the cardiovascular function in healthy mice

Abstract

This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe{sub 2}O{sub 3} NPs (10 mg kg{sup −1}) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1 h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid–base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46 ± 0.02 and 7.41 ± 0.02 in mice 0.5 h after injections of saline or NP, and did not change over the next 12 h. In addition, the injections of NP did not affect arterial PCO{sub 2} or [HCO{sub 3}{sup −}] either. Twenty-four and 96 h after NP injections, the GFR averaged 0.35 ± 0.04 and 0.35 ± 0.01 ml min{sup −1} g{sup −1}, respectively, values which were statistically comparable with controls (0.29 ±more » 0.02 and 0.33 ± 0.1 ml{sup –1} min{sup –1} 25 g{sup –1}). Mean arterial blood pressure (MAP) decreased 12–24 h after NP injections (111.1 ± 11.5 vs 123.0 ± 6.1 min{sup −1}) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterize endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure. -- Highlights: ► PAA coated γ-Fe{sub 2}O{sub 3} nanoparticles were injected intravenously into healthy mice. ► We examine the distribution and physiological effects of nanoparticle accumulation. ► No effects of accumulation in kidney on acid-base status or GFR. ► Acute hypotension associated with decreased contractility of small vessels. ► We demonstrate physiological effects of PAA γ-Fe{sub 2}O{sub 3} NP for medical purposes.« less

Authors:
 [1];  [2]; ;  [3]; ;  [4];  [5];  [6];  [7];  [7]
  1. Department of Biomedicine, Aarhus University (Denmark)
  2. Interdisciplinary Nanoscience Center, Aarhus University (Denmark)
  3. MR Research Center, Aarhus University Hospital, Aarhus University (Denmark)
  4. Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark (Denmark)
  5. Physicochimie des Electrolytes, Colloïdes et Sciences Analytiques (PECSA) UMR 7195 CNRS-UPMC-ESPCI, 4 place Jussieu, 75252 Paris Cedex 05 (France)
  6. Matière et Systèmes Complexes, UMR 7057 CNRS Université Denis Diderot Paris-VII, Bâtiment Condorcet, 10 rue Alice Domon et Léonie Duquet, 75205 Paris (France)
  7. Zoophysiology, Department of Biological Sciences, Aarhus University (Denmark)
Publication Date:
OSTI Identifier:
22216041
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 266; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARTERIES; BLOOD PRESSURE; CYTOPLASM; EXCRETION; FERRITES; HYPOTENSION; INJECTION; IRON OXIDES; LIVER; MICE; NANOSTRUCTURES; NMR IMAGING; RETICULOENDOTHELIAL SYSTEM; SUPERPARAMAGNETISM; TRANSMISSION ELECTRON MICROSCOPY; TUBULES; UPTAKE

Citation Formats

Iversen, Nina K., E-mail: nina.iversen@biology.au.dk, Interdisciplinary Nanoscience Center, Aarhus University, Frische, Sebastian, Thomsen, Karen, Laustsen, Christoffer, Pedersen, Michael, Hansen, Pernille B.L., Bie, Peter, Fresnais, Jérome, Berret, Jean-Francois, Baatrup, Erik, Interdisciplinary Nanoscience Center, Aarhus University, and Wang, Tobias. Superparamagnetic iron oxide polyacrylic acid coated γ-Fe{sub 2}O{sub 3} nanoparticles do not affect kidney function but cause acute effect on the cardiovascular function in healthy mice. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2012.10.014.
Iversen, Nina K., E-mail: nina.iversen@biology.au.dk, Interdisciplinary Nanoscience Center, Aarhus University, Frische, Sebastian, Thomsen, Karen, Laustsen, Christoffer, Pedersen, Michael, Hansen, Pernille B.L., Bie, Peter, Fresnais, Jérome, Berret, Jean-Francois, Baatrup, Erik, Interdisciplinary Nanoscience Center, Aarhus University, & Wang, Tobias. Superparamagnetic iron oxide polyacrylic acid coated γ-Fe{sub 2}O{sub 3} nanoparticles do not affect kidney function but cause acute effect on the cardiovascular function in healthy mice. United States. https://doi.org/10.1016/J.TAAP.2012.10.014
Iversen, Nina K., E-mail: nina.iversen@biology.au.dk, Interdisciplinary Nanoscience Center, Aarhus University, Frische, Sebastian, Thomsen, Karen, Laustsen, Christoffer, Pedersen, Michael, Hansen, Pernille B.L., Bie, Peter, Fresnais, Jérome, Berret, Jean-Francois, Baatrup, Erik, Interdisciplinary Nanoscience Center, Aarhus University, and Wang, Tobias. Tue . "Superparamagnetic iron oxide polyacrylic acid coated γ-Fe{sub 2}O{sub 3} nanoparticles do not affect kidney function but cause acute effect on the cardiovascular function in healthy mice". United States. https://doi.org/10.1016/J.TAAP.2012.10.014.
@article{osti_22216041,
title = {Superparamagnetic iron oxide polyacrylic acid coated γ-Fe{sub 2}O{sub 3} nanoparticles do not affect kidney function but cause acute effect on the cardiovascular function in healthy mice},
author = {Iversen, Nina K., E-mail: nina.iversen@biology.au.dk and Interdisciplinary Nanoscience Center, Aarhus University and Frische, Sebastian and Thomsen, Karen and Laustsen, Christoffer and Pedersen, Michael and Hansen, Pernille B.L. and Bie, Peter and Fresnais, Jérome and Berret, Jean-Francois and Baatrup, Erik and Interdisciplinary Nanoscience Center, Aarhus University and Wang, Tobias},
abstractNote = {This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe{sub 2}O{sub 3} NPs (10 mg kg{sup −1}) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1 h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid–base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46 ± 0.02 and 7.41 ± 0.02 in mice 0.5 h after injections of saline or NP, and did not change over the next 12 h. In addition, the injections of NP did not affect arterial PCO{sub 2} or [HCO{sub 3}{sup −}] either. Twenty-four and 96 h after NP injections, the GFR averaged 0.35 ± 0.04 and 0.35 ± 0.01 ml min{sup −1} g{sup −1}, respectively, values which were statistically comparable with controls (0.29 ± 0.02 and 0.33 ± 0.1 ml{sup –1} min{sup –1} 25 g{sup –1}). Mean arterial blood pressure (MAP) decreased 12–24 h after NP injections (111.1 ± 11.5 vs 123.0 ± 6.1 min{sup −1}) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterize endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure. -- Highlights: ► PAA coated γ-Fe{sub 2}O{sub 3} nanoparticles were injected intravenously into healthy mice. ► We examine the distribution and physiological effects of nanoparticle accumulation. ► No effects of accumulation in kidney on acid-base status or GFR. ► Acute hypotension associated with decreased contractility of small vessels. ► We demonstrate physiological effects of PAA γ-Fe{sub 2}O{sub 3} NP for medical purposes.},
doi = {10.1016/J.TAAP.2012.10.014},
url = {https://www.osti.gov/biblio/22216041}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 2,
volume = 266,
place = {United States},
year = {2013},
month = {1}
}