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Bulletin of Experimental Biology and Medicine

, Volume 168, Issue 1, pp 33–37 | Cite as

Examination of Cardioprotective Effects of Fabomotizole Hydrochloride in Translational Rat Model of Chronic Heart Failure

  • S. A. KryzhanovskiiEmail author
  • I. B. Tsorin
  • V. N. Stolyaruk
  • M. B. Vititnova
  • E. O. Ionova
  • V. V. Barchukov
  • L. M. Kozhevnikova
  • S. B. Seredenin
PHARMACOLOGY AND TOXICOLOGY
  • 6 Downloads

A translational rat model of chronic heart failure was employed to examine the cardioprotective effect of fabomotizole hydrochloride. Fabomotizole therapy for 28 days (15 mg/kg/day intraperitoneally) restored inotropic function of the left ventricle and increased ejection fraction from 54±3 to 65±3% (p=0.001). The inotropic function returned to normal against the background of significantly reduced myocardial expression of angiotensin (p=0.01) and glucocorticoid (p=0.03) receptors and significant increased expression of sigma-1 receptors (p=0.04). Inhibition of abnormal expression of angiotensin and glucocorticoid receptors responsible for activation of the pathological cascades underlying the postinfarction remodeling of the left ventricle as well as activation of the expression of cytoprotective sigma-1 receptors are viewed as the key features of the cardioprotective action of fabomotizole hydrochloride.

Key Words

fabomotizole hydrochloride sigma-1 receptors chronic heart failure receptor expression echocardiography 

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References

  1. 1.
    Kryzhanovskii SA, Tsorin IB, Ionova EO, Stolyaruk VN, Vititnova MB, Barchukov VV, Miroshkina IA, Sorokina AV, Kozhevnikova LM, Durnev AD. A translational model of chronic heart failure in rats. Patol. Fiziol. Eksp. Ter. 2018;62(2):136-148. Russian.Google Scholar
  2. 2.
    Kryzhanovskii SA, Tsorin IB, Sorokina AV, Vititnova MB, Stolyaruk VN, Miroshkina IA, Chichkanov GG, Seredenin SB. Cardioprotective effects of afobazol in animals with chronic myocardial ischemia. Mol. Med. 2013;(5):37-42. Russian.Google Scholar
  3. 3.
    Kryzhanovskyi SA, Sorokina AV, Stolyaruck VN, Vititnova MB, Miroshkina IA, Tsorin IB, Durnev AD, Seredenin SB. Study of anti-ischemic effect of Afobazole in experimental myocardial infarction. Bull. Exp. Biol. Med. 2011;150(3):316-319.CrossRefGoogle Scholar
  4. 4.
    Stolyaruk VN, Vititnova MB, Tsorin IB, Kryzhanovskyi SA. Evaluation of afobasol efficiency on a model of vagotonic atrial fibrillation. Vestn. Ross. Akad. Med. Nauk. 2010;(4):49-52. Russian.Google Scholar
  5. 5.
    Bhuiyan MS, Tagashira H, Fukunaga K. Crucial interactions between selective serotonin uptake inhibitors and sigma-1 receptor in heart failure. J. Pharmacol. Sci. 2013;121(3):177-184.CrossRefGoogle Scholar
  6. 6.
    Bhuiyan MS, Tagashira H, Fukunaga K. Dehydroepiandrosterone-mediated stimulation of sigma-1 receptor activates Akt-eNOS signaling in the thoracic aorta of ovariectomized rats with abdominal aortic banding. Cardiovasc. Ther. 2011;29(4):219-230.CrossRefGoogle Scholar
  7. 7.
    Bhuiyan MS, Tagashira H, Fukunaga K. Sigma-1 receptor stimulation with fluvoxamine activates Akt-eNOS signaling in the thoracic aorta of ovariectomized rats with abdominal aortic banding. Eur. J. Pharmacol. 2011;650(2-3):621-628.CrossRefGoogle Scholar
  8. 8.
    Gray GA, White CI, Castellan RF, McSweeney SJ, Chapman KE. Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardium. J. Mol. Endocrinol. 2017;58(1):R1-R13.CrossRefGoogle Scholar
  9. 9.
    Lijnen PJ, Petrov VV. Role of intracardiac renin-angiotensinaldosterone system in extracellular matrix remodeling. Methods Find. Exp. Clin. Pharmacol. 2003;25(7):541-564.CrossRefGoogle Scholar
  10. 10.
    Oakley RH, Cidlowski JA. Glucocorticoid signaling in the heart: A cardiomyocyte perspective. J. Steroid. Biochem. Mol. Biol. 2015;153:27-34.CrossRefGoogle Scholar
  11. 11.
    Palomeque J, Delbridge L, Petroff MV. Angiotensin II: a regulator of cardiomyocyte function and survival. Front. Biosci. (Landmark Ed). 2009;14:5118-5133.CrossRefGoogle Scholar
  12. 12.
    Patel KP, Schultz HD. Angiotensin peptides and nitric oxide in cardiovascular disease. Antioxid. Redox Signal. 2013;19(10):1121-1132.CrossRefGoogle Scholar
  13. 13.
    Ren R, Oakley RH, Cruz-Topete D, Cidlowski JA. Dual role for glucocorticoids in cardiomyocyte hypertrophy and apoptosis. Endocrinology. 2012;153(11):5346-5360.CrossRefGoogle Scholar
  14. 14.
    Tagashira H, Bhuiyan MS, Fukunaga K. Diverse regulation of IP3 and ryanodine receptors by pentazocine through σ1-receptor in cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 2013;305(8):H1201-H1212.CrossRefGoogle Scholar
  15. 15.
    Tagashira H, Bhuiyan S, Shioda N, Hasegawa H, Kanai H, Fukunaga K. Sigma1-receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice. Am. J. Physiol. Heart Circ. Physiol. 2010;299(5):H1535-H1545.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • S. A. Kryzhanovskii
    • 1
    Email author
  • I. B. Tsorin
    • 1
  • V. N. Stolyaruk
    • 1
  • M. B. Vititnova
    • 1
  • E. O. Ionova
    • 1
  • V. V. Barchukov
    • 1
  • L. M. Kozhevnikova
    • 1
  • S. B. Seredenin
    • 1
  1. 1.V. V. Zakusov Research Institute of PharmacologyMoscowRussia

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