Grman Marian, Balis Peter, Berenyiova Andrea, Svajdlenkova Helena, Tomasova Lenka, Cacanyiova Sona, Rostakova Zuzana, Waczulikova Iveta, Chovanec Miroslav, Domínguez-Álvarez Enrique, Ondrias Karol, Misak Anton
Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska Cesta 9, 845 05, Bratislava, Slovak Republic.
Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Sienkiewiczova 1, 813 71, Bratislava, Slovak Republic.
Biol Trace Elem Res. 2025 Feb;203(2):903-929. doi: 10.1007/s12011-024-04196-3. Epub 2024 Apr 27.
Selenium compounds exert their antioxidant activity mostly when the selenium atom is incorporated into selenoproteins. In our work, we tested the possibility that selenite itself interacts with thiols to form active species that have reducing properties. Therefore, we studied the reduction of 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazol-1-yloxy-3-oxide radical (cPTIO), damage of plasmid DNA (pDNA), modulation of rat hemodynamic parameters and tension of isolated arteries induced by products of interaction of selenite with thiols. We found that the products of selenite interaction with thiols had significant reducing properties that could be attributed mainly to the selenide and that selenite had catalytic properties in the access of thiols. The potency of thiols to reduce cPTIO in the interaction with selenite was cysteine > homocysteine > glutathione reduced > N-acetylcysteine. Thiol/selenite products cleaved pDNA, with superoxide dismutase enhancing these effects suggesting a positive involvement of superoxide anion in the process. The observed cPTIO reduction and pDNA cleavage were significantly lower when selenomethionine was used instead of selenite. The products of glutathione/selenite interaction affected several hemodynamic parameters including rat blood pressure decrease. Notably, the products relaxed isolated mesenteric artery, which may explain the observed decrease in rat blood pressure. In conclusion, we found that the thiol/selenite interaction products exhibited significant reducing properties which can be used in further studies of the treatment of pathological conditions caused by oxidative stress. The results of decreased rat blood pressure and the tension of mesenteric artery may be perspective in studies focused on cardiovascular disease and their prevention.
硒化合物大多在硒原子被整合到硒蛋白中时发挥其抗氧化活性。在我们的研究中,我们测试了亚硒酸盐本身与硫醇相互作用形成具有还原性质的活性物质的可能性。因此,我们研究了2-(4-羧基苯基)-4,5-二氢-4,4,5,5-四甲基-1H-咪唑-1-氧基-3-氧化物自由基(cPTIO)的还原、质粒DNA(pDNA)的损伤、大鼠血流动力学参数的调节以及亚硒酸盐与硫醇相互作用产物诱导的离体动脉张力。我们发现,亚硒酸盐与硫醇相互作用的产物具有显著的还原性质,这主要可归因于硒化物,并且亚硒酸盐在硫醇的参与过程中具有催化性质。硫醇在与亚硒酸盐相互作用中还原cPTIO的能力为半胱氨酸>同型半胱氨酸>还原型谷胱甘肽>N-乙酰半胱氨酸。硫醇/亚硒酸盐产物可切割pDNA,超氧化物歧化酶可增强这些作用,表明超氧阴离子在此过程中起到了积极作用。当使用硒代蛋氨酸代替亚硒酸盐时,观察到的cPTIO还原和pDNA切割明显降低。谷胱甘肽/亚硒酸盐相互作用的产物影响了多个血流动力学参数,包括大鼠血压下降。值得注意的是,这些产物使离体肠系膜动脉舒张,这可能解释了观察到的大鼠血压下降。总之,我们发现硫醇/亚硒酸盐相互作用产物表现出显著的还原性质,可用于进一步研究氧化应激引起的病理状况的治疗。大鼠血压降低和肠系膜动脉张力降低的结果在关注心血管疾病及其预防的研究中可能具有前景。