ENDOTHELIAL PROTECTIVE ACTIVITY OF 2,6-DIISOBORNYL-4-METHYLPHENOL IN A MODEL OF MYOCARDIAL ISCHEMIA/REPERFUSION IN RATS

Authors

  • PETR P. SHCHETININ Laboratory for Modelling of Physical Processes in Biology and Medicine, National Research Tomsk State University, 36 Lenin Ave., Tomsk, Russia.
  • VERA I. SMOL’YAKOVA Laboratory for Circulatory Pharmacology, E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, 3 Lenin Ave., Tomsk, Russia.
  • TATYANA M. PLOTNIKOVA Department of Pharmacology, Siberian State Medical University, 2 Moskovsky Trakt, Tomsk, Russia.
  • ALEKSANDR V. KUCHIN Laboratory for Organic Synthesis and Chemistry of Natural Compounds, Institute of Chemistry, Ural Division of the Russian Academy of Sciences, 48 Pervomayskaya Street, Syktyvkar, Russia.
  • VLADIMIR V. UDUT Laboratory for Modelling of Physical Processes in Biology and Medicine, National Research Tomsk State University, 36 Lenin Ave., Tomsk, Russia.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i12.36004

Keywords:

2,6-diisobornyl-4-methylphenol, Endothelial protective effect, Myocardial ischemiareperfusion, Vascular endothelium

Abstract

Objective: Our research focuses on the endothelial protective effects of 2,6-diisobornyl-4-methylphenol. Its effect was revealed while studying rats experiencing myocardial ischemia/reperfusion. The research results demonstrated that there are significant disturbances in the vascular endothelium manifested by a decrease in the vasodilating activity and antiplatelet properties of 2,6-diisobornyl-4-methylphenol.

Methods: We designed our own model of myocardial ischemia/reperfusion and applied it to 52 adult outbred Wistar males. We employed some methods of hemostasiological research such as thromboelastography to determine the antiplatelet activity of the vascular wall, G. Born nephelometric method to study platelet aggregation, phase contrast microscopy to count platelet counts in blood plasma, measurement of intra-arterial pressure to study the endothelial vasodilating function, and calculated the endothelial dysfunction coefficient in rats.

Results: Preventive intragastric injection of 2,6-diisobornyl-4-methylphenol (100 mg/kg, 3 days before and 5 days after reproducing the myocardial ischemia/reperfusion model) increased the antiplatelet activity of the vascular endothelium in rats by 37% compared to the endothelium of the abdominal aorta segment of untreated animals. Moreover, 2,6-diisobornyl-4-methylphenol decreased the endothelial dysfunction coefficient by 43% in comparison with the value in the control group.

Conclusion: 2,6-diisobornyl-4-methylphenol has an endothelial protective effect proved by its ability to increase antiplatelet properties of the endothelium and decrease the endothelial dysfunction coefficient. The revealed endothelial protective properties of 2,6-diisobornyl-4-methylphenol can be regarded as one of the potential mechanisms of cardioprotective activity of the drug.

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References

World Health Organization. World Health Statistics 2018. Geneva, Switzerland: World Health Organization; 2018.

Forstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 2017;120:713-35.

Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962;194:927-9.

Plotnikov MB, Ivanov IS, Smol’jakova VI, Chernysheva GA, Kuchin AV, Chukicheva IJ, et al. Antioxidant activity of the o-isobornylphenol derivate in rats with cerebral ischemia. Probl Biol Med Pharm Chem 2010;5:23-5.

Plotnikov MB, Smoljakova VI, Ivanov IS, Chernysheva GA, Kuchin AV, Chukicheva IJ, et al. Hemorheological effects of ortho-isobornyl phenol derivative under conditions of brain ischemia in rats. Bull Exp Biol Med 2010;149:721-3.

Plotnikova TM, Chernysheva GA, Smol’jakova VI, Shchetinin PP, Kuchin AV, Chukicheva IJ, et al. Hemorheologic effects of dibornol in a model of myocardial ischemia/reperfusion. Bull Exp Biol Med 2014;157:211-4.

Plotnikova T, Plotnikov M, Chernysheva G, Smol’yakova V, Shchetinin P, Kuchin A, et al. The antiarrhythmic effect of 4-methyl- 2,6-diisobornylphenol in myocardial ischemia/reperfusion. Key Eng Mater 2016;683:469-74.

Kogan AH. Surgical method for modeling coronary occlusion myocardial infarction and aneurysm. Pat Fiz Eksp Ter 1979;3:79-81.

Madigan M, Zuckerbraun B. Therapeutic potential of the nitrite-generated NO pathway in vascular dysfunction. Front Immunol 2013;4:1-9.

do Amaral RJ, da Silva NP, Haddad NF, Lopes LS, Ferreira FD, Filho RB, et al. Platelet-rich plasma obtained with different anticoagulants and their effect on platelet numbers and mesenchymal stromal cells behavior in vitro. Stem Cells Int 2016;2016:7414036.

Todiras M, Alenina N, Bader M. Evaluation of endothelial dysfunction in vivo. Methods Mol Biol 2017;1527:355-67.

Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015;71:40-56.

Allencherril J, Jneid H, Atar D, Alam M, Levine G, Kloner RA, et al. Pathophysiology, diagnosis, and management of the no-reflow phenomenon. Cardiovasc Drugs Ther 2019;15:1-9.

Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol 2004;15:1983-92.

Tiurenkov IN, Voronkov AV. A new methodological approach to the experimental estimation of endothelial dysfunction. Eksp Klin Farmakol 2008;71:49-51.

Farias JG, Molina VM, Carrasco RA, Zepeda AB, Figueroa E, Letelier P, et al. Antioxidant therapeutic strategies for cardiovascular conditions associated with oxidative stress. Nutrients 2017;9:966.

Turer AT. Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy. Am J Cardiol 2010;106:360-8.

Gimbrone MA Jr., Garcia-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016;118:620-36.

Published

07-12-2019

How to Cite

PETR P. SHCHETININ, VERA I. SMOL’YAKOVA, TATYANA M. PLOTNIKOVA, ALEKSANDR V. KUCHIN, and VLADIMIR V. UDUT. “ENDOTHELIAL PROTECTIVE ACTIVITY OF 2,6-DIISOBORNYL-4-METHYLPHENOL IN A MODEL OF MYOCARDIAL ISCHEMIA/REPERFUSION IN RATS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 12, no. 12, Dec. 2019, pp. 49-52, doi:10.22159/ajpcr.2019.v12i12.36004.

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