Magnetometry as an important complementary tool in biomedical research related to the changing levels and forms of iron in the organs of laboratory animals

Investigators: M. Škrátek, J. Maňka

Chronic stress is a risk factor for several chronic non-communicable diseases. The chronic release of glucocorticoids and catecholamines during stress is thought to activate mechanisms that induce oxidative stress and inflammation. The transcription factor NRF2 regulates the expression of genes encoding proteins involved in iron metabolism, as well as antioxidant and detoxification enzymes involved in the antioxidant and anti-inflammatory response. The effects of chronic stress and administration of DMF (dimethyl fumarate, the most potent activator of NRF2) on gene expression of NRF2 (encoded by the Nfe2l2 gene), antioxidant enzymes, and proteins involved in iron metabolism in the liver, blood, and heart of adult male borderline hypertensive rats were investigated. The rats were divided into four groups: control, chronic stress (stress induced by an increase in population density for 6 weeks), DMF-treated rats, and rats exposed to the combined effect of stress and DMF. Stress led to a significant decrease in body weight gain and an increase in plasma total, HDL, and LDL cholesterol concentrations. Using SQUID magnetometry, it was found that remanent magnetization (Mr, a parameter characterizing the magnetic properties of tissue related to changes in the structure and amount of iron-containing compounds) was significantly reduced in the livers of rats exposed to stress. There were no significant changes in magnetic saturation (Ms), Mr, or coercivity (Hc) between groups in the heart. In blood, increased Ms was found in the DMF group. In addition, Ms in blood was positively correlated with plasma Fe2+ levels and with Nfe2l2 gene expression in the heart. It appears that chronic social stress increases the expression of genes encoding both iron influx and efflux into hepatocytes and possibly iron “turnover” in the liver, which may be related to the increased production of iron-containing compounds, especially hemoglobin, due to the increased demands on tissue oxygenation during stress.

Related projects: APVV-22-0296, VEGA 2/0157/21.

The results were achieved in collaboration with the Centre of Experimental Medicine of the Slovak Academy of Sciences, v.v.i., and the Institute of Pharmacology and Clinical Pharmacology of the Faculty of Medicine of the Charles University in Bratislava.

Publications:

• KLUKNAVSKY, M. – BALIS, P. – LISKOVA, S. – MICUROVA, A. – ŠKRÁTEK, Martin – MAŇKA, Ján – BERNATOVA, I. Dimethyl fumarate prevents the development of chronic social stress-induced hypertension in borderline hypertensive rats. In Antioxidants, 2024, vol. 13, no. 8, art. no. 947. ISSN 2076-3921. (6 – IF2023) Q1 (ADMA)
• KLUKNAVSKÝ, M. – MIČUROVÁ, A. – ŠKRÁTEK, Martin – MAŇKA, Ján – BERNÁTOVÁ, I. Účinok chronického sociálneho stresu na génovú expresiu proteínov regulujúcich metabolizmus železa a antioxidačných enzýmov v pečeni hranične hypertenzných potkanov. In Fyziologické dni : Pri príležitosti 100. výročia lekárskej fyziológie na slovensku a 100. výročia Fyziologického ústavu LF UK v Bratislave. – Bratislava : Univerzita Komenského, 2024, s. 99. ISBN 978-80-223-5782-1. (AFH)
• KLUKNAVSKÝ, M. – MIČUROVÁ, A. – ŠKRÁTEK, Martin – MAŇKA, Ján – BERNÁTOVÁ, I. Effects of long-term activation of NRF2 function by DMF under normal and long-term stress conditions in an experimental model of prehypertension. In New Frontiers in Basic Cardiovascular Research France – New EU Members : Program & Book of Abstracts. – Montpellier, France : Physiologie & Medecine Experimentale Coeur Muscles, University of Montpellier, 2024, p. 26