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Gestational Diabetes Mellitus Model and its Pharmacological Validation

https://doi.org/10.33647/2074-5982-21-2-58-70

Abstract

Previous studies have shown the combined effect of short-term nutritional intake and intraperitoneal administration of the nonionic surfactant tyloxapol in the second half of pregnancy in rats on impaired glucose tolerance at its normal fasting level or a moderate increase in blood. This can be regarded as a condition corresponding to gestational diabetes mellitus (GDM), in which DNA damage occurs in embryo cells along with the disorders of the pre- and postnatal development of rat offspring. The proposed GDM biomodel had required pharmacological verification, which was performed in our study using hypoglycemic drugs metformin and glimepiride. The drugs were administered orally from the first day of pregnancy in a 1% starch solution. We assessed the capacity of each drug to reduce or eliminate impaired glucose tolerance and/or moderate hyperglycemia, developmental abnormalities in offspring, DNA damage in embryonic tissues, changes in muscle tone, and formation of unconditioned reflexes in the neonatal period. The behavior of adult offspring was assessed using elevated plus maze, novel object recognition, open field, and others tests. Metformin at a dose of 250 mg/kg showed a weak capacity to reduce impaired glucose tolerance in pregnant rats and to reduce DNA damage levels in embryonic cells, showing no action in other tests. Glimepiride at a dose of 4 mg/kg effectively eliminated carbohydrate metabolism disorders in pregnant rats, reduced DNA damage in fetal liver and brain cells, increased offspring survival, and corrected behavioral abnormalities in offspring. Thus, the results obtained indicate the feasibility of the analyzed experimental model when searching for means of pharmacological correction of GDM and its complications in offspring.

About the Authors

A. S. Solomina
Federal Research Center for Original and Promising Biomedical and Pharmaceutical Technologies
Russian Federation

Anna S. Solomina, Cand. Sci. (Biol.)

125315, Moscow, Baltiyskaya Str., 8



K. S. Kachalov
Federal Research Center for Original and Promising Biomedical and Pharmaceutical Technologies
Russian Federation

Kirill S. Kachalov 

125315, Moscow, Baltiyskaya Str., 8



A. V. Rodina
Federal Research Center for Original and Promising Biomedical and Pharmaceutical Technologies
Russian Federation

Anastasia V. Rodina 

125315, Moscow, Baltiyskaya Str., 8



A. D. Durnev
Federal Research Center for Original and Promising Biomedical and Pharmaceutical Technologies
Russian Federation

Andrey D. Durnev, Dr. Sci. (Med.), Prof., Corr. Member of the Russian Academy of Sciences

125315, Moscow, Baltiyskaya Str., 8



L. G. Kolik
Federal Research Center for Original and Promising Biomedical and Pharmaceutical Technologies
Russian Federation

Larisa G. Kolik, Dr. Sci. (Biol.), Prof. 

125315, Moscow, Baltiyskaya Str., 8



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For citations:


Solomina A.S., Kachalov K.S., Rodina A.V., Durnev A.D., Kolik L.G. Gestational Diabetes Mellitus Model and its Pharmacological Validation. Journal Biomed. 2025;21(2):58-70. (In Russ.) https://doi.org/10.33647/2074-5982-21-2-58-70

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ISSN 2074-5982 (Print)
ISSN 2713-0428 (Online)