Correction of morphofunctional disorders in experimental preeclampsy by combined use of trimetazidine and purified micronized flavonoid fraction as well as their combinations with methylampsy

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Abstract

The aim of the experiment was to determine the effectiveness of the combined use of trimetazidine and a purified micronized flavonoid fraction, as well as their combinations with methyldopa, in comparison with monotherapy with the same drugs in the correction of morphofunctional disorders arising in the conditions of experimental preeclampsia.

An integrated/multimethodology approach is the most effective way of treatment for preeclampsia. Therefore, an urgent task of modern pharmacology is to study the effectiveness of new drugs when used in combinations, as well as the drugs included in the standards for treatment.

Materials and methods. The study was carried out at the Research Institute of Pharmacology of Living Systems of Belgorod State National Research University. The experiment was performed on 200 female Wistar rats, weighing 250–300 g, in which an ADMA-like model of preeclampsia had been reproduced. To assess the degree of correction of emerging morphological and functional disorders, the following parameters were involved: blood pressure, a coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid contents in the greater omentum, morphometric indicators of placental tissues and fetal height and weight parameters.

Results. The combined use of trimetazidine (Preductal® MB) 6 mg/kg and a purified micronized flavonoid fraction (Detralex®) 260 mg/kg, as well as their combination with methyldopa (Dopegit®) 86 mg/kg, leads to a more pronounced decrease in the blood pressure, compared with a decrease in the coefficient of endothelial dysfunction by 2.22, 2.19 and 1.94 times, respectively, in relation to “untreated” animals. There was an increase in microcirculation indices in the placenta by 2.35, 2.21 and 2.03 times, respectively. In addition, there was an improvement in morphological parameters in the placenta and fetuses.

Conclusion. The results of the study showed a greater effectiveness of the combined use of the studied drugs in experimental preeclampsia compared to their monotherapy. This indicates the prospects for the use of trimetazidine and purified micronized flavonoid fraction in the complex therapy for preeclampsia and the need for further research in this direction.

About the authors

Oksana E. Antsiferova

Belgorod State National Research University

Author for correspondence.
Email: AnciferovaO@ya.ru
ORCID iD: 0000-0002-9456-9569

postgraduate student of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, 85, Pobeda St., Belgorod, 308015

Maria P. Teleschenko

Belgorod State National Research University

Email: marijastreltsowa@yandex.ru
ORCID iD: 0000-0003-0849-4351

postgraduate student of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, 85, Pobeda St., Belgorod, 308015

Yulia M. Tsuverkalova

Belgorod State National Research University

Email: cvd404@mail.ru
ORCID iD: 0000-0001-8489-247X

post-graduate student of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, 85, Pobeda St., Belgorod, 308015

Mikhail V. Pokrovsky

Belgorod State National Research University

Email: mpokrovsky@yandex.ru
ORCID iD: 0000-0002-2761-6249

Doctor of Sciences (Medicine), Professor, Professor of the Department of Pharmacology and Clinical Pharmacology, the Head of the Research Institute of Pharmacology of Living Systems

Russian Federation, 85, Pobeda St., Belgorod, 308015

Vladimir V. Gureev

Belgorod State National Research University

Email: produmen@yandex.ru
ORCID iD: 0000-0003-1433-1225

Doctor of Sciences (Medicine), Associate Professor, Professor of the Department of Pharmacology and Clinical Pharmacology

Russian Federation, 85, Pobeda St., Belgorod, 308015

Maria A. Zatolokina

Kursk State Medical University

Email: marika1212@mail.ru
ORCID iD: 0000-0002-9553-1597

Doctor of Sciences (Medicine), Professor, Professor of the Department of Histology, Cytology, Embryology

Russian Federation, 3, Karl Marx St., Kursk, 305041

Anastasia V. Gureeva

Kursk State Medical University

Email: nastasyi.207@gmail.com
ORCID iD: 0000-0003-1719-7316

4th year student of Medical Department

Russian Federation, 3, Karl Marx St., Kursk, 305041

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2. Figure 1 – The effect of the Preductal® MB and Detralex® combination, as well as their combination with Dopegit®, on proteinuria and fluid content in the tissue of the greater omentum in ADMA-like preeclampsiaNote: # – at p <0.05 in comparison with intact pregnant rats; * – at p <0.05 in comparison with the group of pregnant animals treated with L-NAME; y – at p <0.05 in comparison with both monotherapy options.

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3. Figure 2 – The effect of the Preductal® МВ and Detralex® combination, as well as their combination with Dopegit®, on the fetal and maternal size parts of the placenta, in ADMA-like preeclampsiaNote: # – at p <0.05 in comparison with intact pregnant rats; * – at p <0.05 in comparison with the group of pregnant animals treated with L-NAME; y – at p <0.05 in comparison with both monotherapy options

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Copyright (c) 2020 Antsiferova O.E., Teleshchenko M.P., Tsuverkalova Y.M., Pokrovsky M.V., Gureev V.V., Zatolokina M.A., Gureeva A.V.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
 

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