Cardiotropic properties of chromone-3-aldehyde derivatives under an experimental cardiac infarction complicated with hypercholesterolemia

View or download the full article: 
UDC: 
616.127-005.8
Authors: 

A.V. Voronkov1, D.I. Pozdnyakov1, V.M. Rukоvitsyna1, E.T. Oganesyan1, M.P. Voronkova2

Organization: 

1Рyatigorsk Medical Pharmaceutical Institute of Volgograd Medical State University of the Ministry of Health Care of Russia, 11 Kalinin Ave., Pyatigorsk, 357532, Russian Federation
2Volgograd State Medical University, 1 Pavshikh Bortsov Square, Volgograd, 400131, Russian Federation

Abstract: 

Cardiac infarction still remains a leading cause of mortality among population. There are a lot of risk factors causing the disease and complicating it; undoubtedly, they require correction. Our research goal was to experimentally assess cardiotropic peculiarities of 4 chromone-3-aldehyde derivatives (coded as Х3АF, Х3АFOK, X3ANO2, and X3ANO2ОК) as medications aimed at minimizing risks of acute cardiac infarction complicated with hypercholesterolemia. The experiment was performed on 70 male Wistar rats (pubescent, with body weight being equal to 220-240 grams); the animals were divided into 7 equal experimental groups, 10 animals in each. The first group was made up of falsely operated animals. We modeled atherogenesis in 60 remaining rats via oral introduction of 3 % cholesterol dissolved in sunflower oil; the solution was introduced daily for 14 days. We also modeled acute cardiac infarction in them via ligating the left descending coronary artery with a silk thread. After 24 hours we performed electrocardiography to assess changes in QT range, and P, R, and T peaks amplitude. We also determined sizes of necrosis zones and ischemic damage foci in the cardiac muscle via double dying with Evans blue and tetrazolium chloride. We detected that compounds encoded as X3ANO2, X3ANO2OK, X3AF and X3AFOK had hypocholesteremic and cardiotropic effects which led to electrophysiological properties returning to physiological standards and a decrease in ischemia/necrosis zones in the cardiac muscle under cardiac infarction. Objects encoded as X3ANO2OK and X3AFOK were more pharmacologically active than X3ANO2 and X3AF, and X3ANO2OK substance was comparable to a reference medication, Meldonium in our case, in terms of its activity. Overall, the examined substances can be considered medications able to minimize risks of acute cardiac infarction complicated with hypercholesterolemia.

Keywords: 
hypercholesterolemia, cardiac infarction, population mortality, risk factors, ischemia, necrosis, chromone derivatives, Meldonium, cardiac hystiocytes
Voronkov A.V., Pozdnyakov D.I., Rukоvitsyna V.M., Oganesyan E.T., Voronkova M.P. Cardiotropic properties of chro-mone-3-aldehyde derivatives under an experimental cardiac infarction complicated with hypercholesterolemia. Health Risk Analysis, 2019, no. 3, pp. 128–134. DOI: 10.21668/health.risk/2019.3.15.eng
References: 
  1. Zhernakova N.I., Romashchenko O.V., Gorbach T.V., Zvereva V.A., Konstantinov S.L. [et al]. Kliniko-eksperimen-tal'noe issledovanie effektivnosti fosfokreatina pri ishemii miokarda [Clinical and experimental study of the effectiveness of phosphocreatine in myocardial ischemia]. Nauchnye vedomosti BelGU. Seriya: Meditsina. Farmatsiya, 2012, vol. 135, no. 16, pp. 176–181 (in Russian).
  2. Kuz'michev D.E., Vil'tsev I.M., Skrebov R.V., Chirkov S.V. Infarkt miokarda v klinike [Myocardial infarction in the clinic]. Problemy ekspertizy v meditsine, 2015, vol. 57–58, no. 1–2, pp. 49–51 (in Russian).
  3. Shpektor A.V., Vasil'eva E.Yu. New definitions of myocardial infarctions (comments on "Universal definitions of my-ocardial infarction" published in № 5, 2008). Ratsional'naya farmakoterapiya v kardiologii, 2009, vol. 5, no. 1, pp. 112–113 (in Russian).
  4. Mythili S., Malathi N. Diagnostic markers of acute myocardial infarction. Biomedical Reports, 2015, vol. 6, no. 3, pp. 743–748. DOI: 10.3892/br.2015.500
  5. Ilic M., Grujicic Sipetic S., Ristic B. Myocardial infarction and alcohol consumption: A case-control study. PLoS ONE, 2018, vol. 13, no. 6, p. e0198129. DOI: 10.1371/journal.pone.0198129
  6. Libby P., Ridker P.M., Maseri A. Inflammation and atherosclerosis. Circulation, 2002, no. 105, pp. 1135–1143. DOI: 10.1161/hc0902.104353
  7. Cunningham K.S., Gotlieb A.I. The role of shear stress in the pathogenesis of atherosclerosis. Lab. Invest., 2005, no. 85, pp. 9–23. DOI: 10.1038/labinvest.3700299
  8. Reddy K., Khaliq A., Henning R.J. Recent advances in the diagnosis and treatment of acute myocardial infarction. World Journal of Cardiology, 2015, vol. 7, no. 5, pp. 243–276. DOI: 10.4330/wjc.v7.i5.243
  9. Herrett E., Shah A.D., Boggon R., Denaxas S., Smeeth L., Van Staa T., Timmis A., Hemingway H. Completeness and diagnostic validity of recording acute myocardial infarction events in primary care, hospital care, disease registry, and national mortality records: cohort study. The BMJ, 2013, vol. 346, pp.f2350. DOI: 10.1136/bmj.f2350
  10. Mullasari A.S., Balaji P., Khando T. Managing complications in acute myocardial infarction. J. Assoc. Physicians India, 2011, vol. 59, pp. 43–48.
  11. Sadovnikova I.I. Kardioprotektory. Nedootsenennye vozmozhnosti [Cardioprotectors. Underrated opportunities]. Russkii meditsinskii zhurnal, 2009, vol. 17, no. 18, pp. 1132–1134 (in Russian).
  12. Bezuglaya V. Рharmaceuticals possessing both ergogenic and cardioprotective properties in the practice of athletes'' training. Nauka v olimpiiskom sporte, 2016, no. 4, pp. 59–64 (in Russian).
  13. Gunina L.M., Bezuglaya V.V. Cardioprotectors in sports medicine: problems and search for solutions. Sovremennye zdorov'esberegayushchie tekhnologii, 2016, no. 4, pp. 91–101 (in Russian).
  14. Yuzhik E.I., Lushnikova E.L. Medical-biological problems of atherosclerosis modeling. Fundamental'nye issledovaniya, 2012, no. 10–1, pp. 176–183 (in Russian).
  15. Danilenko L.M., Pokrovskii M.V., Kharitonova O.V., Klochkova G.N., Skachilova S.Ya., Kesarev O.G., Be¬lyaev K.A., Khavanskii A.V. Izuchenie protivoishemicheskoi aktivnosti v ryadu proizvodnykh 3-(2, 2, 2-trimetilgidrazinii) propionata pri modelirovanii koronarookklyuzionnogo infarkta miokarda [The study of the antiischemic activity in a number derivatives of 3-(2, 2, 2-trimethylhydrazine) propionate in the simulation koronarolitikov myocardial infarction]. Nauchnye vedomosti BelGU. Seriya: Meditsina. Farmatsiya, 2011, vol. 117, no. 22-2, pp. 5–8 (in Russian).
  16. Xu Q., Li Q.-G., Fan G.-R., Liu Q.-H., Mi F.-L., Liu B. Protective effects of fentanyl preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion in rats. Brazilian Journal of Medical and Biological Research, 2017, vol. 50, no. 2, e5286 p. DOI: 10.1590/1414-431X20165286
  17. Sun X., Cai J., Fan X., Han P., Xie Y., Chen J., Xiao Y., Kang Y.J. Decreases in Electrocardiographic R-Wave Am-plitude and QT Interval Predict Myocardial Ischemic Infarction in Rhesus Monkeys with Left Anterior Descending Artery Liga-tion. PLoS ONE, 2013, no. 8, рp. e71876. DOI: 10.1371/journal.pone.0071876
  18. Nancy T., Subin M.Z. Pharmacological Activities Of Chromene Derivatives: An Overview. Asian Journal Of Phar-maceutical And Clinical Research, 2013, vol. 6, pp. 11–15.
  19. Jarr K.U., Eschricht S., Burkly L.C., Preusch M., Katus H.A., Frey N., E. Chorianopoulos. TNF-Like Weak Inducer of Apoptosis Aggravates Left Ventricular Dysfunction after Myocardial Infarction in Mice. Mediators of Inflammation, 2014, Article ID 131950. Available at: https://www.hindawi.com/journals/mi/2014/131950/ (23.04.2019)
  20. Frangogiannis N.G. The inflammatory response in myocardial injury, repair and remodeling. Nature reviews Cardiol-ogy, 2014, vol. 11, no. 5, pp. 255–265. DOI: 10.1038/nrcardio.2014.28
  21. Fridén-Saxin M., Seifert T., Landergren M.R., Suuronen T., Lahtela-Kakkonen M., Jarho E.M., Luthman K. Synthesis and Evaluation of Substituted Chroman-4-one and Chromone Derivatives as Sirtuin 2-Selective Inhibitors. Journal of Medicinal Chemistry, 2012, vol. 16, no. 55, pp. 7104–7113. DOI: 10.1021/jm3005288
  22. Yu J., Auwerx J. The role of sirtuins in the control of metabolic homeostasis. Annals of the New York Academy of Sci-ences, 2009, no. 1173, pp. E10–E19. DOI: 10.1111/j.1749-6632.2009.04952.x
Received: 
19.04.2018
Accepted: 
20.07.2019
Published: 
30.09.2019

You are here