Sytnyk I. Pharmacological approach into administration of N-acetylcysteine and losartan in cardiac disorders of type 1 diabetes mellitus

The dissertation deals with experimental studying of cardioprotective properties of N-acetylcysteine and losartan for pharmaco-correction of cardiac disorders in case of type 1 diabetes mellitus. The results in vitro were indicated drugs-leaders for the antioxidant activity (N-acetylcysteine and losartan) and the quantum-chemical descriptors of drugs-leaders were made in silico. The cardioprotective effect of N-acetylcysteine (at a dose of 1500 mg/kg) was shown by the restoration of the cardiac rhythm, decreasing the manifestations of myocardial hypertrophy, reduction in HbA1C, decrease the cardiac damage markers and cytolysis. The membrane-protective effects of N-acetylcysteine contributed to increase in the stearic acid content. N-acetylcysteine has indicated better endothelial protective effect; prevented the process of remodeling in the left ventricle (decreased expression of MMP-2). The cardioprotective effect of N-acetylcysteine was realized through the activation of the autophagal system by ultrastructural studies. Cardioprotective effect of losartan (at a dose of 20 mg/kg) was associated with restoration of myocardial depolarization and repolarization, reducing of CPK-MB activity. The membrane protective properties of losartan contribute to the redistribution of minor fatty acids. The antiproliferative effect of losartan was associated with an increase activity of matrix metalloproteinase type 9. The combined administration of N-acetylcysteine at a dose of 750 mg/kg and losartan at a dose of 2,0 mg/kg caused the most significant cardioprotective effect, as indicated by the restoration of indicators of general physical condition, normalization of contractile function, reduction of manifestations of hypertrophy and fibrosis, improvement of energy and trophic properties of the myocardium.