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

Valery I Kapelko,Alexander A Abramov,Elena V Lukoshkova,Nidas A Undrovinas,Asker Y Khapchaev,Vladimir L Lakomkin,Vladimir P Shirinsky

doi:10.1155/2017/9456163

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.

Highlights

Oxidative stress in cells occurs when reactive oxygen species (ROS) prevail over the means of antioxidant protection
In order to determine an optimal concentration of Oxacom to be used during hypoxic perfusion, we studied this compound across the concentration range of 0.01–2.7 μM in oxygenated hearts
The coronary flow rate was monitored as the main parameter as the increased rate under constant perfusion pressure indicates a decreased tone of the coronary vessels

Summary

Introduction

Oxidative stress in cells occurs when reactive oxygen species (ROS) prevail over the means of antioxidant protection. A deep fall in contractile function allows them to conserve limited stores of ATP and phosphocreatine This is realized by means of limiting Ca2+ entry into cells [1] due to the shortening of action potential and early release of K+, which gradually reduces excitability of cardiomyocytes. 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. 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.

Methods

Results

Conclusion