Changes in the Deformability and Resistance of Erythrocyte Membranes under the Action of Gamma-Aminobutyric Acid Derivatives in the Offspring of Rats with Experimental Preeclampsia

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Abstract

INTRODUCTION: Preeclampsia is a severe complication of pregnancy associated with the negative consequences for the mother and child. Such complications can be a reduction in the resistance of erythrocyte membranes to damaging agents and alteration of rheological properties of the blood in offspring. Promising compounds for the correction of these negative consequences of preeclampsia are gamma-aminobutyric acid (GABA) derivatives, which showed membrane–protective, antioxidant, and antihypoxic effects in previous studies.

AIM: To evaluate the effect of GABA derivatives Succicard® (4-phenylpiracetam and ethane-1,2-dicarboxylic acid, 2:1), Salifen® (4-amino-3-phenylbutanoic acid and 2-hydroxybenzoic acid, 2:1), and Phenibut® (aminophenylbutyric acid) on the deformability and resistance of erythrocyte membranes in 8- and 14-month-old offspring of rats with experimental preeclampsia (EP).

MATERIALS AND METHODS: The study involved offspring (male and female) of white non-inbred female rats with a normal pregnancy and EP that was modeled by replacement of drinking water with a 1.8% sodium chloride solution during gestation (1–21 days). For 30 days (from day 40 to day 70 of life), pup rats intragastrically received Succicard® (22 mg/kg), Salifen® (7.5 mg/kg), and Phenibut® (25 mg/kg), along with a comparison drug Pantogam® (calcium gopantenate) (50 mg/day) once a day. The offspring of the positive and negative control groups were injected with distilled water in a similar mode. In offspring aged 8 and 14 months, the resistance of erythrocyte membranes to the action of hydrochloric acid and their deformability were determined.

RESULTS: In 8-month-old male offspring of rats with EP, a shorter time of achievement of half the maximal amplitude of erythrogram was noted in acid hemolysis relative to the positive control group, and the erythrocyte elongation index was reduced. Relative to the negative control group, Succicard®, Salifen®, Phenibut®, and Pantogam® promoted the prolongation of hemolysis and the erythrocyte elongation index in 8-month-old male rats in the experimental groups. In 14-month-old male and female rats of different ages, no statistically significant differences were found between the groups.

CONCLUSION: Changes in the stiffness and strength of erythrocyte membranes were noted only in male offspring of rats with EP. Succicard®, Salifen®, Phenibut®, and Pantogam® produced membrane-protective effects on the erythrocytes of 8-month-old male rats of the experimental groups.

About the authors

Elena A. Muzyko

Volgograd State Medical University

Author for correspondence.
Email: muzyko.elena@mail.ru
ORCID iD: 0000-0003-0535-9787
SPIN-code: 9939-9414

MD, Cand. Sci. (Med.), assistant at the department of theoretical biochemistry with a course in clinical biochemistry

Russian Federation, Volgograd

Lyudmila V. Naumenko

Volgograd State Medical University

Email: milanaumenko@mail.ru
ORCID iD: 0000-0002-2119-4233
SPIN-code: 8537-0991

MD, Associate Professor, doctor of science (Medicine), assistant professor, professor of the department of pharmacology and bioinformatics

Russian Federation, Volgograd

Valentina N. Perfilova

Volgograd State Medical University; Scientific Center for Innovative Medicines

Email: vnperfilova@mail.ru
ORCID iD: 0000-0002-2457-8486
SPIN-code: 3291-9904

doctor of science (Biology), professor, professor of the department of pharmacology and pharmacy

Russian Federation, Volgograd; Volgograd

Valeriya E. Zavadskaya

Volgograd State Medical University

Email: valzavadskaya@yandex.ru
ORCID iD: 0000-0003-0772-8371

student of 4 course of the Pharmacy Faculty

Russian Federation, Volgograd

Sof’ya V. Varlamova

Volgograd State Medical University

Email: varlamovasophia@yandex.ru
ORCID iD: 0000-0002-4242-9863

student of 4 course of the Pharmacy Faculty

Russian Federation, Volgograd

Ivan N. Tyurenkov

Volgograd State Medical University

Email: fibfuv@mail.ru
ORCID iD: 0000-0001-7574-3923
SPIN-code: 6195-6378

HFRHE RF, HSW RF, corresponding member of RAS, MD, doctor of science (Medicine), professor, head of the department of pharmacology and pharmacy of Institute of Continuing Medical and Pharmaceutical Education

Russian Federation, Volgograd

Ol’ga S. Vasil'yeva

The Herzen State Pedagogical University of Russia

Email: kohrgpu@yandex.ru
ORCID iD: 0000-0002-7779-8861
SPIN-code: 9820-9881

candidate of science (Chemistry), senior researcher of Problem Laboratory of Nitro Compounds, Department of Organic Chemistry

Russian Federation, Saint-Petersburg

References

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Supplementary files

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2. Fig. 1. Effect of gamma-aminobutyric acid derivatives on the duration of reaching one-half of the maximal amplitude in the erythrogram (Т1/2 of hemolysis) in 8-month-old (A) and 14-month-old (B) offspring of rats with experimental preeclampsia (M ± m). Note: * p < 0.05 in comparison with the data of the positive control group (Student’s t-test); # p < 0.05 in comparison with the data of the negative control group (Newman–Keuls test).

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3. Fig. 2. Effect of gamma-aminobutyric acid derivatives on erythrocyte elongation index in 8-month-old (A) and 14-month-old (B) offspring of rats with experimental preeclampsia (M ± m). Note: * p < 0.05 in comparison with the data of the positive control group (Student’s t-test); # p < 0.05 in comparison with the data of the negative control group (Newman–Keuls test).

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