Correction of morphofunctional disturbances arising when modelling Preeclampsia with resveratrol and nicorandil

Ступакова, Е. Г.; Лазарева, Г. А.; Гуреев, В. В.

doi:10.3897/rrpharmacology.4.25528

Cited by 6 publications

(5 citation statements)

References 34 publications

(29 reference statements)

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“…In the context of our study of the activity of pHBSP in experimental preeclampsia, it should be noted that the chosen model of preeclampsia has an ischemic component despite the fact that it is caused by a vasoactive ADMA-like substance. Apparently, placental vessels are most sensitive to L-NAME, which causes their spasm and subsequent ischemia up to necrotic alteration [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Korokin

Гуреев

Гудырев

et al. 2020

IJMS

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Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Korokin

Гуреев

Гудырев

et al. 2020

IJMS

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“…Activation of KATP channels seems to play a predominant role in these effects where glibenclamide reduced significantly but not completely the effect of nicorandil. [52] In addition, the capability of nicorandil to relax the uterine muscle, which was mainly achieved through KATP channels, can improve the placental microcirculation. [53]…”

Section: Different Mechanisms Involved In Different Diseased Conditionsmentioning

confidence: 99%

Nicorandil: A drug with ongoing benefits and different mechanisms in various diseased conditions

Ahmed

2019

Indian J Pharmacol

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Nicorandil is a well-known antianginal agent, which has been recommended as one of the second-line treatments for chronic stable angina as justified by the European guidelines. It shows an efficacy equivalent to that of classic antianginal agents. Nicorandil has also been applied clinically in various cardiovascular diseases such as variant or unstable angina and reperfusion-induced damage following coronary angioplasty or thrombolysis. Different mechanisms have been involved in the protective effects of nicorandil in various diseases through either opening of adenosine triphosphate-sensitive potassium (KATP) channel or donation of nitric oxide (NO). The predominance or participation of any of these proposed mechanisms depends on the dose of nicorandil used, the location of diseased conditions, and if this mechanism is still functioning or not. The protection afforded by nicorandil has been shown to be mainly attributed to KATP channel opening in experimental models of myocardial and pulmonary fibrosis as well as renal injury or glomerulonephritis, whereas NO donation predominates as a mechanism of protection in hepatic fibrosis and inflammatory bowel diseases. Therefore, in different diseased conditions, it is important to know which mechanism plays the major role in nicorandil-induced curative or protective effects. This can bring new insights into the proper use of selected medication and its recommended dose for targeting certain disease.

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“…В экпериментальных исследованиях на модели L-NAME-индуцированной преэклампсии у крыс были продемонстрированы протективные свойства резвератрола [17,18], рекомбинантного эритропоэтина [19], тадалафила [20,21], обладающих эндотелиопротективными свойствами. Другим перспективным направлением профилактики и коррекции морфофункциональных нарушений, возникающих при преэклампсии, является применение препаратов с противоишемическими и антиоксидантными свойствами.…”

Section: Introductionunclassified

Correction of Morphofunctional Disorders in Experimental Preeclampsy by Combined Use of Trimetazidine and Purified Micronized Flavonoid Fraction as Well as Their Combinations With Methylampsy

Анциферова

Телещенко

Цуверкалова

et al. 2021

Farm. farmakol. (Pâtigorsk)

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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.

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Correction of morphofunctional disturbances arising when modelling Preeclampsia with resveratrol and nicorandil

Abstract: Introduction: Preeclampsia is one of the most serious diseases of the second half of pregnancy and is surely amongst the top three causes of maternal mortality. Therefore, the creation of new drugs for preventing and correcting preeclampsia is an urgent task.

Cited by 6 publications

References 34 publications

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Nicorandil: A drug with ongoing benefits and different mechanisms in various diseased conditions

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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