Characteristics of influence of 4-[4-oxo-3 h-quinazoline-3-yl] benzoic acid (pc-66) on a course of adrenaline myocardiodystrophy in rats according to biochemical research

O. V. Dzhyhaliuk, H. I. Stepaniuk, N. V. Zaichko, S. I. Kovalenko, K. P. Shabelnyk

Abstract


According to the literature the leading cause of mortality among the population of Ukraine are cardiovascular diseases, what incidence tripled over the past 25 years and today stands at801.6 in100 000. It necessitates a search for new chemical compounds, suitable for creating manufacturing with a better safety profile and a high degree of efficiency.

The aim of the study was to describe the effect of 4-[4-oxo-4N-quinazoline-3- il] benzoic acid (PC-66), compared with kordaron on the processes of free radical oxidation, endothelial nitric oxide production and activity of marker enzymes cytolysis cardiomyocytes adrenaline myocardiodystrophy (AMD) in rats.

The study was conducted on 28 nonlinear rats of both sexes (weight – 165–220 grams), divided into four groups: group I (n = 7) – intact rats; group II (n = 7) – rats with untreated AMD (control); group III (n = 7) – rats with AMD treated with entity PC-66 (10 mg/kg intraperitoneally (i/p)); Group IV (n = 7) – rats with AMD treated with kordaron (10 mg/kg, i/p).

Research shown that the development of a pilot AMD in rats was characterized by increased free radical oxidation processes, depletion of antioxidant defense system (with decreased content of G-SH, activity of superoxide dismutase and glutathione peroxidase), oppression of endothelial NO production. The most expressive metabolic disturbances were registered in the acute period of AMD (as of 2nd day). The use of 4-[4-oxo-4N-quinazoline-3-il] benzoic acid (PC-66, 10 mg/kg, i/p) provided an expressive cardioprotective effect which was compared with kordaron (10 mg/kg, i/p) at various stages of AMD.

The mechanisms of cardioprotective action 4-[4-oxo-4N-quinazoline-3-il] benzoic acid can be realized due to the stabilization of cellular and subcellular membranes (as evidenced by the dynamics of marker enzymes cytolysis cardiomyocytes in serum and reduction of TBA-reactive substances in the myocardium), increasing the efficiency of the antioxidant system and correction of cellular redox buffer (as evidenced by the increasing pool of reduced glutathione, glutathione peroxidase and superoxide dismutase activity increased) and anti-ischemic activity associated with increased activity of endothelial NO synthase in cardiac muscle.


Keywords


adrenaline myocardial dystrophy; cordarone; 4-[4-oxo-4H-quinazoline-3-il] benzoic acid; cardioprotective activity.

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DOI: http://dx.doi.org/10.11603/mcch.2410-681X.2016.v0.i4.7249

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