title: Superparamagnetic iron oxide polyacrylic acid coated γ-Fe2O3 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(2)O(3) NPs (10 mg kg(-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 1h 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(2) or [HCO(3)(-)] either. Twenty-four and 96 h after NP injections, the GFR averaged 0.35±0.04 and 0.35±0.01 ml min(-1) g(-1), respectively, values which were statistically comparable with controls (0.29±0.02 and 0.33±0.1 ml(-1) min(-1) 25 g(-1)). Mean arterial blood pressure (MAP) decreased 12-24 h after NP injections (111.1±11.5 vs 123.0±6.1 min(-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.
authors.affiliation: Zoophysiology, Department of Biological Sciences, Aarhus University, Denmark. nina.iversen@biology.au.dk
authors.forename: Nina K
authors.initials: NK
authors.lastname: Iversen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Frische
authors.forename: Karen
authors.initials: K
authors.lastname: Thomsen
authors.forename: Christoffer
authors.initials: C
authors.lastname: Laustsen
authors.forename: Michael
authors.initials: M
authors.lastname: Pedersen
authors.forename: Pernille B L
authors.initials: PB
authors.lastname: Hansen
authors.forename: Peter
authors.initials: P
authors.lastname: Bie
authors.forename: Jérome
authors.initials: J
authors.lastname: Fresnais
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Berret
authors.forename: Erik
authors.initials: E
authors.lastname: Baatrup
authors.forename: Tobias
authors.initials: T
authors.lastname: Wang
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry*; D005919:Glomerular Filtration Rate; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D009119:Muscle Contraction / Q000187:drug effects; D009213:Myography; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000180:Acrylic Resins; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; C006903:carbopol 940