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Information × Registration Number 0226U002725, (0124U001684) , R & D reports Title Redox-dependent mechanisms of changes in cardiovascular function in aging and doxorubicin-induced heart failure. popup.stage_title Функціонування серцево-судинної системи при експериментальній DOX-індукованій серцевій недостатності (кардіотоксичності) у щурів та в умовах активації ендогенних механізмів захисту. Head Sagach Vadym F., д.мед.н. Registration Date 04-03-2026 Organization Bogomolets Institute of Physiology of the National Academy of Sciences of Ukraine popup.description1 The aim of this study is to investigate redox-dependent mechanisms of changes in cardiovascular function in aging and doxorubicin(DOX)-induced heart failure. Particular attention will be paid to DOX-induced mitochondrial dysfunction in the rat heart and the role of ATP-sensitive potassium channels (KATP channels) as well as endogenous antioxidants - glutathione and gas transmitters. It is known that KATP channels are universal regulators of cellular functions and metabolism, which determines their key role in defense mechanisms. The work will investigate the functioning of the cardiovascular system in experimental DOX-induced heart failure (cardiotoxicity) in rats and in conditions of activation of endogenous defense mechanisms. Also, the search for antioxidant agents for the correction of cardiac disorders of different genesis (aging, DOX-induced heart failure) will be carried out, in particular the effect of KATP channel openers and new nanomaterials as potential antioxidants, etc. The role of melatonin deficiency (hypomelatoninemia) in the development of cardiac mitochondrial dysfunction will be established and the functional state of the cardiovascular system under conditions of inhibition of endogenous melatonin synthesis will be studied. popup.description2 In vivo experiments were conducted to investigate changes in electrocardiogram (ECG) waves in adult rats under conditions of doxorubicin (DOX) administration and co-administration of DOX and flocalin. The results of the ECG study concluded that DOX-induced cardiotoxicity is associated with ECG changes indicating impaired conduction, automaticity, contractility, and acute ischemic myocardial injury. QT interval prolongation, ST segment elevation, changes in heart rate, and decreased R wave amplitude are characteristic consequences of such damage caused by DOX administration. For the first time, it was demonstrated that the simultaneous administration of flocalin, a fluorine-containing activator of KATP channels, significantly attenuated DOX-induced ECG abnormalities. The study also demonstrated an increase in the activity of enzymes (early markers of doxocardiotoxicity: AST, ALT, and CPK-MB) in the blood plasma of rats under the influence of DOX, as well as the membrane-stabilizing effect of CATP channel activation. Systemic deficiency of the endogenous antioxidant hydrogen sulfide was established under the influence of DOX, as well as partial restoration of its plasma concentration upon KATP channel activation. This can be considered an early marker of cardiovascular disorders and one of the mechanisms of DOX's cardiotoxic action. Significant increases in voltage-dependent anion channel (Vdac1) expression, a component of the transient conductance mitochondrial pore, were also demonstrated. This may indicate increased mitochondrial membrane conductivity and contribute to heart failure development. Thus, the process of DOX-induced heart damage is accompanied by cardiomyocyte membrane damage and is manifested by bradycardia and conduction disturbances, and signs of myocardial ischemia. Positive changes on the ECG under the action of flocalin confirm its cardioprotective and anti-ischemic effect. Product Description popup.authors Yuliia P. Korkach Tetiana A. Ilina Nataliia A. Strutynska Lidiia A. Mys Olga V. Dmytrenko Iryna Y. Okhai Yuliia O. Bubnova Vadym F. Sahach Yuliia V. Hoshovska popup.nrat_date 2026-03-04 Close