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
DOI:
https://doi.org/10.11603/mcch.2410-681X.2016.v0.i4.7249Keywords:
adrenaline myocardial dystrophy, cordarone, 4-[4-oxo-4H-quinazoline-3-il] benzoic acid, cardioprotective activity.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.
References
Metabolitnye i metabolitotropnye preparaty v sisteme kardio- i organoprotektcii / I. S. Chekman, N. A. Gorchakova, S. B. Frantcuzova, E. A. Nagornaia. – K., 2009. – 155 s.
2. Moibenko A. A. Endogennye mekhanizmy kardioprotektcii kak osnova patogeneticheskoi terapii zabolevanii serdtca / A. A. Moibenko, V. E. Dosenko, A. N. Parkhomenko. – K. : Naukova dumka, 2008. – 518 s.
Нетяженко В. З. Цитопротекція міокарда в лікуванні хворих на ішемічну хворобу серця / В. З. Нетяженко, Н. В. Нетяженко, Т. Й. Мальчевська // Артериальная гипертензия. – 2015. – № 3 (41). – С. 40–50.
Netiazhenko V. Z. Tsytoprotektsiia miokarda v likuvanni khvorykh na ishemichnu khvorobu sertsia / V. Z. Netiazhenko, N. V. Netiazhenko, T. I. Malchevska // Arteryalnaia hypertenzyia. – 2015. – № 3 (41). – S. 40–50.
Markova O. O. Miokardiodystrofiia i reaktyvnist orhanizmu / O. O. Markova. – Ternopil : Ukrmedknyha, 1998. – 150 s.
Alchuk O. I. Aktoprotektorni vlastyvosti novykh pokhidnykh 4-okso(amino-)-khinazolinu (eksperymentalne doslidzhennia) : avtoref. dys. na zdobuttia nauk. stupenia kand. med. nauk / O. I. Alchuk. – K., 2011. – 21 s.
Dzhyhaliuk O. V. Kharakterystyka kardioprotektornykh vlastyvostei pokhidnoho 4-okso-(amino-) khinazolinu (spoluky PK-66) za umov hostroi koronarnoi ishemii / O. V. Dzhyhaliuk, H. I. Stepaniuk, S. I. Kovalenko // Farmakolohiia ta likarska toksykolohiia. – 2011. – № 5 (24). – S. 97–98.
Владимиров Ю. В. Перекисное окисление липидов в биологических мембранах / Ю. В. Владимиров, А. И. Арчаков. – М. : Наука, 1972. – 252 с.
Ellman G. L. Tissue Sulfhydryl groups // Arch. of Bioch. and Biophys. – 1956. –Vol. 82. – P. 70–77.
Kostiuk V. A. Prostoi i chuvstvitelnyi metod opredeleniia aktivnosti superoksiddismutazy, osnovannyi na reaktcii okisleniia kvertcetina / V. A. Kostiuk, A. I. Potapovich, Zh. V. Kovaleva // Vopr. med. khimii. – 1990. – № 2. – S. 88–91.
Vlasova S. N. Aktivnost glutation-zavisimykh fermentov eritrotcitov pri khronicheskikh zabolevaniiakh pecheni u detei / S. N. Vlasova, E. I. Shabunina, I. A. Pereligina // Lab. delo. – 1990. – № 8. – S. 19–22.
Hula N. M. Vplyv N-stearoiletanolaminu na NO-syntaznyi shliakh heneratsii oksydu azotu v aorti ta sertsi shchuriv iz streptozototsynindukovanym diabetom / N. M. Hula, H. V. Kosiakova, A. H. Berdyshev // Ukr. biokhim. zhurn. – 2007. – 79, № 5. – S. 153–158.
Lapach S. N. Statisticheskie metody v mediko-biologicheskikh issledovaniiakh s ispolzovaniem Excel / S. N. Lapach, A. V. Chubenko, P. N. Babich. – K. : Morion, 2001. – 320 s.S-glutathionylation in protein redox regulation / I. Dalle-Donne, R. Rossi, D. Giustarini // Free Radic. Biol. Med. – 2007. – Vol. 43, № 6. – Р. 883–898.
Preventive effect of amiodarone during acute period in isoproterenol-induced myocardial injury in Wistar rats / F. Albayrak, Y. Bayir, Z. Halici // Cardiovasc. Toxicol. – 2009. – Vol. 9, № 4. – Р. 161–168.
Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling / U. Fоrstermann, Н. Li // Br. J. Pharmacol. – 2011. – Vol. 164, № 2. – Р. 213–223.
Otsinka analhetychnoi aktyvnosti v riadi novykh pokhidnykh 4-okso (amino) khinazolinu / H. I. Stepaniuk, I. D. Alchuk, S. I. Kovalenko [ta in.] / Farmakolohiia ta likarska toksykolohiia : IV Nats. z’izd farmakolohiv Ukrainy : tezy dop. – 2011. – № 5 (24). – S. 308–309.
