Book of Abstracts - New Frontiers 2022

Abstracts of oral presentations

TISSUE- AND STRAIN-DEPENDENT DIFFERENCES IN IRON METABOLISM AFTER SINGLE ADMINISTRATION OF IRON OXIDE NANOPARTICLES

M. Kluknavsky 1 , A. Micurova 1 , P. Balis 1 , M. Skratek 2 , J. Manka 2 , I. Bernatova 1

1 Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia; 2 Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia We investigated the effect of polyethylene glycol-coated Fe3O4 nanoparticles (IONs) on mean arterial pressure (MAP) and heart rate (HR) in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) after single intravenous administration of IONs (1 mg Fe/kg). In the liver and left heart ventricle (LHV) of both strains, we determined nitric oxide (NO) production, superoxide (O2•– ) production, ION originated iron and biogenic iron content. Finely, we investigated expression of genes involved in iron metabolism, antioxidant defence and NO production in both tissues. IONs administration did not affect MAP and HR in both strains and led to increased deposition of ION originated iron in tissues of WKY compared to SHR. Our findings showed strain differences of biogenic iron content in the liver (↓WKY and ↑SHR) and LHV (↑WKY and ↓SHR). In WKY, IONs treatment increased O2•– production in both tissues with unaltered NO production. In SHR, ION treatment reduced liver NO production without effect on O2•– production in both tissues. In the liver, IONs administration increased expression of the hepcidin gene in both strains which product has a crucial role in iron regulation. IONs treatment also increased gene expression of antioxidants superoxide dismutase 1 and 2 (Sod1 and Sod2) in WKY with opposite trends in SHR. Strain differences after IONs treatment were also noted in the expression of the H- ferritin (Fth1; ↑WKY and ↓SHR) and transferrin (Tf; unchanged in WKY and ↓SHR) genes, whose products represent the major intracellular iron storage protein and circulating iron transporter. In the LHV, IONs administration significantly decreased expression of antioxidant glutathione peroxidase 4 (Gpx 4) and transcription factor peroxisome proliferator-activated receptor gamma in WKY with similar trends in SHR. Strain differences after IONs administration were also noted in the expression of the transferrin receptor (unchanged in WKY and ↑SHR) which product is responsible for iron endocytosis. Our study showed that despite increased expression of antioxidant genes (Sod1 and Sod2) and genes involved in iron utilization (Fth1), there is a risk of tissue damage in normotensive WKY which tended to accumulate and subsequently utilize exogenous iron despite increased oxidative stress. At the same time, we did not detected oxidative stress in hypertensive SHR after IONs administration, despite the reduced expression of antioxidant genes (Sod1, Sod2 and Gpx4). Unchanged oxidative status in SHR was probably associated with decreased exogenous iron accumulation and repression of iron utilization genes (Fth1 and Tf). However, questions arise about possible negative effects after repeated or prolonged administration of IONs, mainly in normotensive and partly in hypertensive individuals.

Keywords: nanoparticles, nitric oxide, iron metabolism

Funding: This research was funded by grants VEGA 2/0160/17, VEGA 2/164/17 and APVV-16 0263.

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