This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe(2)O(3) NPs (10mgkg(-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 0.5h after injections of saline or NP, and did not change over the next 12h. In addition, the injections of NP did not affect arterial PCO(2) or [HCO(3)(-)] either. Twenty-four and 96h after NP injections, the GFR averaged 0.35±0.04 and 0.35±0.01mlmin(-1)g(-1), respectively, values which were statistically comparable with controls (0.29±0.02 and 0.33±0.1ml(-1) min(-1) 25g(-1)). Mean arterial blood pressure (MAP) decreased 12-24h after NP injections (111.1±11.5 vs 123.0±6.1min(-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.
Toxicology and Applied Pharmacology, 2013, Vol 266, Issue 2, p. 276-88