Evaluation of the pharmacological activity of a somatostatin-containing protein-based preparation in a model of cyclophosphamide-induced ovarian failure in female mice
- Authors: Matichin A.A.1, Kryshen K.L.1, Faustova N.M.1, Gushchin Y.A.1, Makarova M.N.1, Reshetnik V.V.2, Sukhikh G.T.3, Yudin S.M.4, Lunin V.G.5
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Affiliations:
- RMC “HOME OF PHARMACY”
- Yurspharm LLC
- Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
- Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency
- National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya, Ministry of Health of Russia
- Issue: No 7 (2023)
- Pages: 119-125
- Section: Original Articles
- URL: https://journals.rcsi.science/0300-9092/article/view/274615
- DOI: https://doi.org/10.18565/aig.2023.150
- ID: 274615
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Abstract
According to statistical studies, the number of infertile couples in the world is constantly growing and accounts for approximately 15%. Female infertility makes up 20–35%. The new drug being developed on the basis of somatostatin-containing protein is supposed to be used in female and male infertility, to increase the reproductive capacity of the body, to enhance the ovarian reserve and their entry into the growth phase, to accelerate the beginning of growth of resting follicles, to expand the volume of ejaculate and improve the quality characteristics of sperm.
Objective: Evaluation of the pharmacological activity of a somatostatin-containing protein-based preparation in a model of cyclophosphamide-induced ovarian failure in female mice.
Materials and methods: The drug "Endoxan" was used as an inducer of pathology once intraperitoneally at a dose of 70 mg/kg. Six groups were formed for the study: 1st – intact (n=15); 2nd – negative control (pathology+sodium chloride solution 0.9%, n=10); 3rd – positive control (pathology+recombinant murine somatotropic hormone at a dose of 800 µg/kg, n=10); 4th – pathology+test subject at a dose of 10 µg/kg (n=15); 5th – pathology+test subject at a dose of 50 µg/kg (n=15), 6th – pathology+test subject at a dose of 250 µg/kg (n=15).
The study included evaluation of microscopic changes in ovarian tissue, ovarian mass ratios, morphometric analysis of follicles, and plasma PGE2 and somatotropin levels.
Results: It was found that against the background of induced pathology the tested drug in the dose range of 10–250 µg/kg leads to a dose-dependent increase in the level of somatotropin and PGE2 and normalisation of folliculogenesis. It was revealed that a significant increase in the proportion of primordial and tertiary follicles and a decrease in the proportion of atretic follicles occurred under the effect of the tested preparation. This suggests a possible mechanism of action of the tested object, namely the synthesis of specific autoantibodies to somatostatin and a decrease in its concentration. This in turn leads to an increase in the content of endogenous somatotropic and sex hormones in the body.
Conclusion: The results obtained are consistent with the data of earlier studies on the increase in the size and number of follicles upon administration of exogenous somatotropic hormone to animals. We believe that clinical studies of the possibility of using a preparation based on somatostatin-containing protein for the treatment of female infertility associated with disorders of folliculogenesis are necessary.
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##article.viewOnOriginalSite##About the authors
Aleksandr A. Matichin
RMC “HOME OF PHARMACY”
Author for correspondence.
Email: matichin.aa@doclinika.ru
ORCID iD: 0000-0001-7478-4942
Deputy Head of the Department of Specific Toxicology and Pharmacodynamics
Russian Federation, 188663, Leningrad region, Vsevolozhsk district, p. Kuzmolovsky, Zavodskay str. 3, 245Kirill L. Kryshen
RMC “HOME OF PHARMACY”
Email: matichin.aa@doclinika.ru
ORCID iD: 0000-0003-1451-7716
PhD (Bio), Head of the Department of Specific Toxicology and Microbiology
Russian Federation, 188663, Leningrad region, Vsevolozhsk district, p. Kuzmolovsky, Zavodskay str. 3, 245Natalya M. Faustova
RMC “HOME OF PHARMACY”
Email: matichin.aa@doclinika.ru
ORCID iD: 0000-0002-5557-1287
PhD (Chem), Head of the Laboratory of Enzyme Immunoassay
Russian Federation, 188663, Leningrad region, Vsevolozhsk district, p. Kuzmolovsky, Zavodskay str. 3, 245Yaroslav A. Gushchin
RMC “HOME OF PHARMACY”
Email: matichin.aa@doclinika.ru
ORCID iD: 0000-0002-7656-991X
Head of the Laboratory Diagnostics Department
Russian Federation, 188663, Leningrad region, Vsevolozhsk district, p. Kuzmolovsky, Zavodskay str. 3, 245Marina N. Makarova
RMC “HOME OF PHARMACY”
Email: matichin.aa@doclinika.ru
ORCID iD: 0000-0003-3176-6386
Dr. Med. Sci., Director
Russian Federation, 188663, Leningrad region, Vsevolozhsk district, p. Kuzmolovsky, Zavodskay str. 3, 245Vyacheslav V. Reshetnik
Yurspharm LLC
Email: matichin.aa@doclinika.ru
Director
Russian Federation, 117041, Moscow, Admiral Rudnev str., 4, office 6/31/1Gennady T. Sukhikh
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: matichin.aa@doclinika.ru
Academician of the Russian Academy of Sciences, Dr. Med. Sci., Professor, Honoured Scientist of the Russian Federation, Director
Russian Federation, 117997, Moscow, Oparina str., 4Sergei M. Yudin
Centre for Strategic Planning and Management of Biomedical Health Risks of the Federal Medical Biological Agency
Email: matichin.aa@doclinika.ru
Dr. Med. Sci., Professor, Director General
Russian Federation, 119121, Moscow, Pogodinskaya str., 10 bld. 1Vladimir G. Lunin
National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya, Ministry of Health of Russia
Email: matichin.aa@doclinika.ru
Dr. Bio. Sci., Leading Researcher
Russian Federation, 123098, Moscow, Gamaleya str., 18References
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