Ścibior Agnieszka, Hus Iwona, Mańko Joanna, Jawniak Dariusz
Laboratory of Oxidative Stress, Centre for Interdisciplinary Research, The John Paul II Catholic University of Lublin, Poland.
Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
J Trace Elem Med Biol. 2020 Sep;61:126550. doi: 10.1016/j.jtemb.2020.126550. Epub 2020 May 15.
The current knowledge about the effects of vanadium (V) on iron (Fe)-related proteins and Fe homeostasis (which is regulated at the systemic, organelle, and cellular levels) is still insufficient.
This fact and our earlier results prompted us to conduct studies with the aim to explain the mechanism of anemia accompanied by a rise in hepatic and splenic Fe deposition in rats receiving sodium metavanadate (SMV) separately and in combination with magnesium sulfate (MS).
We demonstrated for the first time that SMV (0.125 mg V/mL) administered to rats individually and in conjunction with MS (0.06 mg Mg/mL) for 12 weeks did not cause significant differences in the hepatic hepcidin (Hepc) and hemojuvelin (HJV) concentrations, compared to the control. In comparison with the control, there were no significant changes in the concentration of transferrin receptor 1 (TfR1) in the liver of rats treated with SMV and MS alone (in both cases only a downward trend of 14% and 15% was observed). However, a significant reduction in the hepatic TfR1 level was found in rats receiving SMV and MS simultaneously. In turn, the concentration of transferrin receptor 2 (TfR2) showed an increasing trend in the liver of rats treated with SMV and/or MS.
The experimental data suggest that the pathomechanism of the SMV-induced anemia is not associated with the effect of V on the concentration of Hepc in the liver, as confirmed by the unaltered hepatic HJV and TfR1 levels. Therefore, further studies are needed in order to check whether anemia that developed in the rats at the SMV administration (a) results from the inhibitory effect of V on erythropoietin (EPO) production, (b) is related to the effect of V on the induction of matriptase-2 (TMPRSS6) expression, or (c) is associated with the influence of this metal on haem synthesis.
目前关于钒（V）对铁（Fe）相关蛋白及铁稳态（在全身、细胞器和细胞水平受到调控）影响的知识仍不充分。
鉴于这一事实以及我们早期的研究结果，我们开展了相关研究，旨在解释在分别给予大鼠偏钒酸钠（SMV）以及联合硫酸镁（MS）的情况下，大鼠出现贫血并伴有肝脏和脾脏铁沉积增加的机制。
我们首次证明，单独给予大鼠SMV（0.125 mg V/mL）以及联合MS（0.06 mg Mg/mL）处理12周后，与对照组相比，肝脏中血浆铁调素（Hepc）和血幼素（HJV）的浓度并无显著差异。与对照组相比，单独使用SMV和MS处理的大鼠肝脏中转铁蛋白受体1（TfR1）的浓度没有显著变化（两种情况下仅观察到14%和15%的下降趋势）。然而，同时接受SMV和MS的大鼠肝脏中TfR1水平显著降低。相反，转铁蛋白受体2（TfR2）的浓度在接受SMV和/或MS处理的大鼠肝脏中呈上升趋势。
实验数据表明，SMV诱导贫血的发病机制与V对肝脏中Hepc浓度的影响无关，这一点通过肝脏HJV和TfR1水平未改变得到证实。因此，需要进一步研究以检查在给予SMV的大鼠中发生的贫血（a）是否源于V对促红细胞生成素（EPO）产生的抑制作用，（b）是否与V对matriptase-2（TMPRSS6）表达的诱导作用有关，或者（c）是否与这种金属对血红素合成的影响有关。
