STUDY OF ENDOTHELIOPROTECTIVE ACTION OF COMBINED MEDICINE UNDER ALCOHOLIC CARDIOMYOPATHY

Abstract

At present, due to spreading of alcoholic cardiomyopathy among the able-bodied population of industrialized countries, there is an urgent need to search for new medicines possessing a strictly targeted effect, taking into account the complex mechanisms of the damaging effects produced by ethyl alcohol on the myocardium. Therefore, the combination of L-arginine and thiotriazolin (developed by “Farmatron” scientific production association) is of great clinical interest. The same is relevant for Mildronate, Mexidol and Thiotriazolin. The aim of this research was to study the endothelioprotective effect of the medicine combining L-arginine with thiotriazoline (4: 1) (Argitril) in comparison with the standard metabolites as Mildronate, Mexidol, and Thiotirazoline on the morphological and functional characteristics of endotheliocytes and ST2 level in modelled cardiomyopathy and alcohol cardiomyopathy. Alcoholic cardiomyopathy was caused by intragastric administration of 20% ethanol solution in a dose of 8 g/kg for 90 days. All animals were divided into 5 groups, 10 animals in each. All the studied substances were administered intraperitoneally for 30 days: the combined medicine (L-arginine 100 mg/ml + thiotriazolin 25 mg/ml (4:1)) - 200 mg/kg (in recalculation for L-arginine); Mildronate (Grindeks, Latvia) - 250 mg/kg; Mexidol (NPK Farmasoft, Russia) - 200 mg/kg, Thiotriazolin (Galichfarm, Ukraine) - 50 mg/kg. The control and intact groups received physiological saline. The following indicators were assessed: endothelial cell nucleus area (μm2); the density of the nuclei of endotheliocytes (as an indicator for the number of cell nuclei per 1 mm2 of myocardial tissue area) and the relative area of endotheliocytes (%), ST2 protein.
 The study has shown that on the 30th day after 90 days of the development of alcohol addiction, the animals were found out to have alcoholic cardiomyopathy. A significant decrease, by 32.38%, in the area of the nuclei of endotheliocytes was observed in the animals of the test group, the density of nuclei of the endotheliocytes lowered by 7% and the relative area of the nuclei of the endotheliocytes reduced by 21.89%. An increase in the concentration of ST2 protein was observed in 3.34 times compared with the intact animals that evidences the presence of endothelial dysfunction.
 It has been experimentally proved that the combination of L-arginine/thiotriazolin significantly exceeds the reference medicines as Mildronate, Mexidol and Thiotriazolin in terms of endothelioprotective and cardioprotective effects (effect on the area and density of nuclei of endotheliocytes; concentration of ST2 protein).