Protective Effects of Dinitrosyl Iron Complexes under Oxidative Stress in the Heart

Abstract

Background. Nitric oxide can successfully compete with oxygen for sites of electron-transport chain in conditions of myocardial hypoxia. These features may prevent excessive oxidative stress occurring in cardiomyocytes during sudden hypoxia-reoxygenation. Aim. To study the action of the potent stable NO donor dinitrosyl iron complex with glutathione (Oxacom®) on the recovery of myocardial contractile function and Ca2+ transients in cardiomyocytes during hypoxia-reoxygenation. Results. The isolated rat hearts were subjected to 30 min hypoxia followed by 30 min reoxygenation. The presence of 30 nM Oxacom in hypoxic perfusate reduced myocardial contracture and improved recovery of left ventricular developed pressure partly due to elimination of cardiac arrhythmias. The same Oxacom concentration limited reactive oxygen species generation in hypoxic cardiomyocytes and increased the viability of isolated cardiomyocytes during hypoxia from 12 to 52% and after reoxygenation from 0 to 40%. Oxacom prevented hypoxia-induced elevation of diastolic Ca2+ level and eliminated Ca2+ transport alterations manifested by slow Ca2+ removal from the sarcoplasm and delay in cardiomyocyte relaxation. Conclusion. The potent stable NO donor preserved cardiomyocyte integrity and improved functional recovery at hypoxia-reoxygenation both in the isolated heart and in cardiomyocytes mainly due to preservation of Ca2+ transport. Oxacom demonstrates potential for cardioprotection during hypoxia-reoxygenation.

Protective Effect of Dinitrosyl Iron Complexes with Glutathione in Red Blood Cell Lysis Induced by Hypochlorous Acid

“…Our previous studies established that DNIC increase the elasticity of RBCs and inhibit their detergent-induced lysis [27]. Moreover, DNIC fulfil the function of NO and nitrosonium ion (NO + ) donors; this remarkable capability determines their high physiological activity [20, 22, 28]. The antioxidant and cytoprotective effects of DNIC on living cells and systems under conditions of oxidative stress [28–33] prompt a conclusion that in-depth study of DNIC effects on HOCl-induced lysis of RBСs is a task of paramount importance.…”

Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes

“…Their structure and properties has been studied previously by X-ray diffraction analysis, IR-, Mössbauer- and EPR spectroscopy ( Figure 1, Supplement Material ) (Shmatko et al, 2017a). DNICs serve as carriers of the “ready-to-use”, iron-stabilized form of NO (Kapelko et al, 2017; Schiewer et al, 2019). It was shown that the mechanism of NO release from iron–sulfur complexes in aqueous solution is similar to the generation of NO in the solutions of monocation iron complex with thiocarbamide [Fe(SC(NH 2 ) 2 ) 2 (NO) 2 ]ClH 2 O (Sanina et al, 2014a; Sanina et al, 2015).…”

“…The most common drugs in term of treatment cardiovascular disease are nitroglycerin, nitrosorbid, nitroprusside, and nitrite, which release NO in cells and tissues during their metabolism (Münzel and Schulz, 2010; Kapelko et al, 2017; Gatzke et al, 2018; Liu et al, 2019; Lu et al, 2019; Zhao et al, 2019). However, these drugs are often unstable, non-specific, toxic, and have a number of side effects (Tardiolo et al, 2019).…”

“…In recent years, the interest in the study of nitrosyl complexes of transition metals, particularly iron complexes possessing cytoprotective properties, increases exponentially (Lewandowska et al, 2011). However, such compounds are often poorly soluble in water, short-lived and toxic to the body (Kapelko et al, 2017). Additionally, molecular mechanism of their action and the metabolic effects in cells are not well understood.…”

Why Myocardial Relaxation Always Slows at Cardiac Pathology?

“…Кальциевый транспорт, как рассмотрено ранее, в высокой степени зависит от энергоснабжения, и митохондрии служат ключевым звеном этого процесса. Неудивительно, что при нарушении окислительного фосфорилирования в митохондриях, возникающего при гипоксии или ишемии миокарда, структура кальциевых пиков резко изменяется -они становятся удлиненными, не всегда согласованными с ритмом возбуждений; повышается и диастолический уровень кальциевых сигналов [41].…”