RESUMO
This study investigated genotype- and tissue-related differences in the biodistribution of superparamagnetic magnetite (Fe3O4) nanoparticles (IONs) into the heart and liver of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats after a single i.v. infusion of polyethylene glycol-coated IONs (~30 nm, 1mg Fe/kg) 100 min post-infusion. The effects of IONs on the expression of selected genes involved in the regulation of iron metabolism, including Nos, Sod and Gpx4, and their possible regulation by nuclear factor (erythroid-derived 2)-like 2 (NRF2, encoded by Nfe2l2) and iron-regulatory protein (encoded by Irp1) were investigated. In addition, superoxide and nitric oxide (NO) production were determined. Results showed reduced ION incorporations into tissues of SHR compared to WKY and in the hearts compared to the livers. IONs reduced plasma corticosterone levels and NO production in the livers of SHR. Elevated superoxide production was found only in ION-treated WKY. Results also showed differences in the regulation of iron metabolism on the gene level in the heart and liver. In the hearts, gene expressions of Nos2, Nos3, Sod1, Sod2, Fpn, Tf, Dmt1 and Fth1 correlated with Irp1 but not with Nfe2l2, suggesting that their expression is regulated by mainly iron content. In the livers, expressions of Nos2, Nos3, Sod2, Gpx4, and Dmt1 correlated with Nfe2l2 but not with Irp1, suggesting a predominant effect of oxidative stress and/or NO.
RESUMO
In this study, magnetite nanoparticles were prepared and coated with poly(ethylene glycol) terminated by alendronate to ensure firm binding to the iron oxide surface. Magnetic nanoparticles, designated as magnetite coated with poly(ethylene glycol)-alendronate (Fe3O4@PEG-Ale), were characterized in terms of number-average (Dn) and hydrodynamic (Dh) size, ζ-potential, saturation magnetization, and composition. The effect of particles on blood pressure, vascular functions, nitric oxide (NO), and superoxide production in the tissues of spontaneously hypertensive rats, as well as the effect on red blood cell (RBC) parameters, was investigated after intravenous administration (1 mg Fe3O4/kg of body weight). Results showed that Fe3O4@PEG-Ale particles did negatively affect blood pressure, heart rate and RBC deformability, osmotic resistance and NO production. In addition, Fe3O4@PEG-Ale did not alter functions of the femoral arteries. Fe3O4@PEG-Ale induced increase in superoxide production in the kidney and spleen, but not in the left heart ventricle, aorta and liver. NO production was reduced only in the kidney. In conclusion, the results suggest that acute intravenous administration of Fe3O4@PEG-Ale did not produce negative effects on blood pressure regulation, vascular function, and RBCs in hypertensive rats.
RESUMO
This study aimed to develop the method for determination of the ultra-small superparamagnetic iron oxide nanoparticle (USPION)-originated iron (UOI) in the tissues of rats on the basis of the magnetic characteristics (MC) in the liver, left heart ventricle (LHV), kidneys, aorta and blood of Wistar-Kyoto (WKY). Rats were treated intravenously by USPIONs dispersed in saline (transmission electron microscope (TEM) mean size ~30 nm, hydrodynamic size ~51 nm, nominal iron content 1 mg Fe/mL) at the low iron dose of 1 mg/kg. MC in the form of the mass magnetisation (M) versus the magnetic field (H) curves and temperature dependences of M (determined using the SQUID magnetometer), histochemical determination of iron (by Perl's method) and USPION-induced superoxide production (by lucigenin-enhanced chemiluminescence) were investigated 100 min post-infusion. USPIONs significantly elevated superoxide production in the liver, LHV, kidney and aorta vs. the control group. Histochemical staining confirmed the presence of iron in all solid biological samples, however, this method was not suitable to unequivocally confirm the presence of UOI. We improved the SQUID magnetometric method and sample preparation to allow the determination of UOI by measurements of the MC of the tissues at 300 K in solid and liquid samples. The presence of the UOI was confirmed in all the tissues investigated in USPIONs-treated rats. The greatest levels were found in blood and lower amounts in the aorta, liver, LHV and kidneys. In conclusion, we have improved SQUID-magnetometric method to make it suitable for detection of low amounts of UOI in blood and tissues of rats.