IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION

The aim of the study is to perform an immunohistochemical analysis of the expression of the vascular endothelial growth factor receptor 2 (VEGFR2) in the myocardium of Wistar rats in doxorubicin-induced cardiomyopathy and the administration of betulonic acid amide as an agent with a polytarget effec...

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Main Authors: L. L. Elena, M. M. Mzhelskaya, E. V. Koldysheva, M. G. Klinnikova
Format: Article
Language:Russian
Published: Russian Academy of Sciences, Siberian Branch Publishing House 2019-02-01
Series:Сибирский научный медицинский журнал
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Online Access:https://sibmed.elpub.ru/jour/article/view/76
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author L. L. Elena
M. M. Mzhelskaya
E. V. Koldysheva
M. G. Klinnikova
author_facet L. L. Elena
M. M. Mzhelskaya
E. V. Koldysheva
M. G. Klinnikova
author_sort L. L. Elena
collection DOAJ
description The aim of the study is to perform an immunohistochemical analysis of the expression of the vascular endothelial growth factor receptor 2 (VEGFR2) in the myocardium of Wistar rats in doxorubicin-induced cardiomyopathy and the administration of betulonic acid amide as an agent with a polytarget effect in comparison with the severity of destructive processes in heart muscle cells. Material and methods. Wistar male rats (total 51 animals) were used in the work with isolated and combined administration of a single sublethal dose of doxorubicin (7 mg/kg) and course administration of betulonic acid amide at doses of 50 mg/kg/day and 100 mg/kg/day for 3 and 14 days. Immunohistochemical evaluation of VEGFR2 expression in the myocardium was carried out with the calculation of the index of VEGFR2-positive cardiomyocytes; the volume density of cardiomyocytes with lytic changes was estimated using stereological analysis. Results and discussion. A single administration of doxorubicin (at a dose of 7 mg/kg) caused destructive changes in cardiomyocytes and hemodynamic disorders in myocardium, which increased with the duration of the experiment (14 days). The complex of the revealed structural and metabolic lesions reflected the development of regenerative-plastic insufficiency of cardiomyocytes, which is the basis of cardiac insufficiency in anthracycline cardiomyopathy. Morphological changes in the myocardium with isolated administration of betulonic acid amide were largely determined by the dose used. At a dose of 100 mg/kg, myocardial changes were similar in severity with doxorubicin-induced changes. Combined use of doxorubicin and betulonic acid amide revealed the most significant structural damage of the myocardium. It was shown that the increase in the volume density of lytic altered cardiomyocytes correlated with a significant increase in VEGFR2 expression (correlation coefficient varied from 0.620 to 0.980).
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spelling doaj-art-0eda06dae09b486c95f93c3297145e462025-08-20T03:50:44ZrusRussian Academy of Sciences, Siberian Branch Publishing HouseСибирский научный медицинский журнал2410-25122410-25202019-02-0138651210.15372/SSMJ2018060176IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATIONL. L. Elena0M. M. Mzhelskaya1E. V. Koldysheva2M. G. Klinnikova3Institute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational MedicineInstitute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational MedicineInstitute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational MedicineInstitute of Molecular Pathology and Pathomorphology, Federal Research Center of Fundamental and Translational MedicineThe aim of the study is to perform an immunohistochemical analysis of the expression of the vascular endothelial growth factor receptor 2 (VEGFR2) in the myocardium of Wistar rats in doxorubicin-induced cardiomyopathy and the administration of betulonic acid amide as an agent with a polytarget effect in comparison with the severity of destructive processes in heart muscle cells. Material and methods. Wistar male rats (total 51 animals) were used in the work with isolated and combined administration of a single sublethal dose of doxorubicin (7 mg/kg) and course administration of betulonic acid amide at doses of 50 mg/kg/day and 100 mg/kg/day for 3 and 14 days. Immunohistochemical evaluation of VEGFR2 expression in the myocardium was carried out with the calculation of the index of VEGFR2-positive cardiomyocytes; the volume density of cardiomyocytes with lytic changes was estimated using stereological analysis. Results and discussion. A single administration of doxorubicin (at a dose of 7 mg/kg) caused destructive changes in cardiomyocytes and hemodynamic disorders in myocardium, which increased with the duration of the experiment (14 days). The complex of the revealed structural and metabolic lesions reflected the development of regenerative-plastic insufficiency of cardiomyocytes, which is the basis of cardiac insufficiency in anthracycline cardiomyopathy. Morphological changes in the myocardium with isolated administration of betulonic acid amide were largely determined by the dose used. At a dose of 100 mg/kg, myocardial changes were similar in severity with doxorubicin-induced changes. Combined use of doxorubicin and betulonic acid amide revealed the most significant structural damage of the myocardium. It was shown that the increase in the volume density of lytic altered cardiomyocytes correlated with a significant increase in VEGFR2 expression (correlation coefficient varied from 0.620 to 0.980).https://sibmed.elpub.ru/jour/article/view/76myocardiumcardiomyocytesdoxorubicinbetulonic acid amidevascular endothelial growth factor receptor 2immunohistochemistry
spellingShingle L. L. Elena
M. M. Mzhelskaya
E. V. Koldysheva
M. G. Klinnikova
IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION
Сибирский научный медицинский журнал
myocardium
cardiomyocytes
doxorubicin
betulonic acid amide
vascular endothelial growth factor receptor 2
immunohistochemistry
title IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION
title_full IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION
title_fullStr IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION
title_full_unstemmed IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION
title_short IMMUNOHISTOCHEMICAL EVALUATION OF VASOENDOTHELIAL GROWTH FACTOR RECEPTOR-2 (VEGFR2) EXPRESSION IN RAT CARDIOMYOCYTES UNDER DOXORUBICIN AND BETULONIC ACID AMIDE ADMINISTRATION
title_sort immunohistochemical evaluation of vasoendothelial growth factor receptor 2 vegfr2 expression in rat cardiomyocytes under doxorubicin and betulonic acid amide administration
topic myocardium
cardiomyocytes
doxorubicin
betulonic acid amide
vascular endothelial growth factor receptor 2
immunohistochemistry
url https://sibmed.elpub.ru/jour/article/view/76
work_keys_str_mv AT llelena immunohistochemicalevaluationofvasoendothelialgrowthfactorreceptor2vegfr2expressioninratcardiomyocytesunderdoxorubicinandbetulonicacidamideadministration
AT mmmzhelskaya immunohistochemicalevaluationofvasoendothelialgrowthfactorreceptor2vegfr2expressioninratcardiomyocytesunderdoxorubicinandbetulonicacidamideadministration
AT evkoldysheva immunohistochemicalevaluationofvasoendothelialgrowthfactorreceptor2vegfr2expressioninratcardiomyocytesunderdoxorubicinandbetulonicacidamideadministration
AT mgklinnikova immunohistochemicalevaluationofvasoendothelialgrowthfactorreceptor2vegfr2expressioninratcardiomyocytesunderdoxorubicinandbetulonicacidamideadministration