Abstract:
Nitrosyl iron complexes are remarkably multifactorial pharmacological agents. These compounds have been proven to be particularly effective in treating cardiovascular and oncological diseases. We evaluated and compared the antioxidant activity of tetranitrosyl iron complexes (TNICs) with thiosulfate ligands and dinitrosyl iron complexes (DNICs) with glutathione (DNIC-GS) or phosphate (DNIC-PO4-) ligands in hemoglobin-containing systems. The studied effects included the production of free radical intermediates during hemoglobin (Hb) oxidation by tert-butyl hydroperoxide, oxidative modification of Hb, and antioxidant properties of nitrosyl iron complexes. Measuring luminol chemiluminescence revealed that the antioxidant effect of TNICs was higher compared to DNIC-PO4-. DNIC-GS either did not exhibit antioxidant activity or exerted prooxidant effects at certain concentrations, which might have resulted from thiyl radical formation. TNICs and DNIC-PO4- efficiently protected the Hb heme group from decomposition by organic hydroperoxides. DNIC-GS did not exert any protective effects on the heme group; however, it abolished oxoferrylHb generation. TNICs inhibited the formation of Hb multimeric forms more efficiently than DNICs. Thus, TNICs had more pronounced antioxidant activity than DNICs in Hb-containing systems.
摘要:
亚硝基铁络合物是非常多因素的药理学试剂。这些化合物已被证明在治疗心血管和肿瘤疾病方面特别有效。我们评估并比较了含血红蛋白系统中四硝基铁配合物(TNIC)与硫代硫酸盐配体的抗氧化活性以及二硝基铁配合物(DNIC)与谷胱甘肽(DNIC-GS)或磷酸盐(DNIC-PO4-)配体的抗氧化活性。研究的影响包括叔丁基过氧化氢在血红蛋白(Hb)氧化过程中产生自由基中间体,Hb的氧化改性,亚硝基铁配合物的抗氧化性能。测量鲁米诺化学发光表明,与DNIC-PO4-相比,TNIC的抗氧化作用更高。DNIC-GS在某些浓度下没有表现出抗氧化活性或发挥促氧化作用,这可能是由硫基自由基形成引起的。TNIC和DNIC-PO4-有效地保护Hb血红素基团免受有机氢过氧化物的分解。DNIC-GS对血红素组没有任何保护作用;然而,它废除了氧铁蛋白生成。TNIC比DNIC更有效地抑制Hb多聚体形式的形成。因此,在含Hb的系统中,TNICs比DNICs具有更明显的抗氧化活性。