Cardioprotective effect of hydroxybenzoic acid ester containing neuroactive acid, compound F-26, in conditions of isoproterenol heart failure in rats

Abstract

Introduction: Currently, chronic heart failure (CHF) is one of the leading problems of modern healthcare. Its most common manifestation is the deterioration of the inotropic reserves of the heart muscle, which over time leads to decompensation and damage to internal organs. Mitochondrial dysfunction and oxidative stress cause the progression of heart failure. A number of hydroxybenzoic acid derivatives and neuroactive acids limit mitochondrial dysfunction and oxidative stress, thereby reducing their damaging effect on the heart muscle due to.

Materials and methods: Chronic heart failure (CHF) was modeled by intraperitoneal administration of L-isoproterenol to male Wistar rats at a dose of 2.5 mg 2 times a day for 21 days. An increase in preload was modeled by a single injection of physiological saline into the jugular vein at a rate of 0.3 ml per 100 g of rat weight. Adrenoreceptors were stimulated by 0.1 ml of adrenaline diluted at 10^-7 g/ml per 100 g of rat weight. An increase in afterload was achieved by 30 s occlusion of the ascending aortic arch. The rate of oxygen uptake by mitochondria was determined using the polarographic method. Morphometric study of the myocardium was performed using microphotographs.

Results and discussion:  Compound F-26, a derivative of hydroxybenzoic acid containing neuroactive acid, has a positive effect on the inotropic reserves of the cardiac muscle, as indicated by an increase in the growth of myocardial contraction and relaxation rates, as well as left ventricular pressure and maximum intensity of structural performance (MISP) during exercise tests. Compound F-26, a derivative of phenolic acid, limits the manifestations of oxidative stress, as indicated by a decrease in the concentration of MDA, as well as an increase in SOD activity. Morphometric analysis of cardiomyocytes showed that compound F-26 has a positive effect on the cross-sectional area, thickness, volume fraction of cardiomyocytes and interstitium.

Conclusion: The compound F-26, an ester of hydroxybenzoic acid containing a neuroactive acid in its composition, has a cardioprotective effect in conditions of isoproterenol heart failure in rats, comparable to the comparison drug mildronate, as indicated by an improvement in the inotropic function of the heart, the functioning of mitochondria, the antioxidant system in cardiomyocytes and morphometric parameters.

Graphical Abstract