Experimental model of non-alcoholic fatty liver disease in pregnant rats to evaluate the effectiveness of therapy

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Abstract

Background: The growing incidence of non-alcoholic fatty liver disease in the population contributes to the development of obstetric complications during pregnancy and demands searching effective methods of hepatoprotective therapy.

Aim: The aim of this study was to evaluate the efficacy of therapy for non-alcoholic fatty liver disease in an experimental model in pregnant rats.

Materials and methods: this experimental study was carried out on 19 female Wistar rats weighing 250–300 g, obtained from the laboratory animal nursery of SMK Stezar Ltd. (Vladimir, Russia). Using a high-fat diet, non-alcoholic fatty liver disease was simulated in the study groups as follows. Group 1 (n = 7) consisted of non-pregnant rats, group 2 comprised pregnant rats without therapy (n = 6), and group 3 included pregnant rats and intraperitoneal administration of 12 mg of the low-molecular sugar preparation from day 16 to day 20 of gestation (n = 6). During the experiment, the body weight of female rats was measured weekly. After the experiment was completed, we evaluated the blood serum levels of aspartate aminotransferase, alanine aminotransferase, ferritin, triglycerides, total cholesterol, total bilirubin, urea, total alkaline phosphatase, bile acids, glucose, C-reactive protein, cholinesterase, and malondialdehyde, as well as catalase activity. Histological examination of the rat liver was carried out using the standard method with hematoxylin and eosin staining.

Results: This study showed that high-fat diet caused oxidative stress manifested by decreased the blood catalase level and increased malonovodialdehyde in both pregnant and non-pregnant females; the blood bile acids level also increased. In pregnant rats with non-alcoholic fatty liver disease, the serum C-reactive protein and total alkaline phosphatase levels increased, the cholinesterase level decreased, and the catalase activity decreased even more. In the study group using the low-molecular sugar preparation, biochemical parameters in non-alcoholic fatty liver disease improved, probably due to the effect on lipogenesis and oxidative stress in the liver. The histological pattern was characterized by the impaired structural characteristics of hepatocytes and the circulatory bed. With the use of the low-molecular-weight sugar preparation, we noted a tendency to restore the structure of the hepatic beam area and a decrease in the manifestations of steatosis.

Conclusions: The use of the low-molecular-weight sugar preparation in the treatment of non-alcoholic fatty liver disease improves biochemical blood parameters and tends to restore the histological structure of the liver.

About the authors

Elena V. Mozgovaia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: elmozg@mail.ru
ORCID iD: 0000-0002-6460-6816
SPIN-code: 5622-5674

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Marina A. Kryshnia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: Marina._k@mail.ru
ORCID iD: 0009-0000-2502-1578

MD

Russian Federation, Saint Petersburg

Alexandra А. Blazhenko

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: alexandradlazhenko@gmail.com
SPIN-code: 8762-3604

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Alina А. Nuzhnova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: lin.panaiotis@yandex.ru
SPIN-code: 5521-5096
Russian Federation, Saint Petersburg

Gulrukhsor Tolibova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: gulyatolibova@yandex.ru
ORCID iD: 0000-0002-6216-6220
SPIN-code: 7544-4825

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Tatyana G. Tral

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: ttg.tral@yandex.ru
ORCID iD: 0000-0001-8948-4811
SPIN-code: 1244-9631

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Janna N. Toumasova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: J_toumassa@mail.ru
SPIN-code: 2352-0755
Russian Federation, Saint Petersburg

Andrey V. Korenevsky

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: a.korenevsky@yandex.ru
ORCID iD: 0000-0002-0365-8532
SPIN-code: 7942-6016

Dr. Sci. (Biology)

Russian Federation, Saint Petersburg

Irina V. Zalozniaia

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: irinabiolog2012@yandex.ru
ORCID iD: 0000-0002-0576-9690
SPIN-code: 2488-3790

Cand. Sci. (Biology)

Russian Federation, Saint Petersburg

Victoria S. Ganzhina

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: ganzhina040799@gmail.com
ORCID iD: 0009-0001-5225-6484
Russian Federation, Saint Petersburg

Olesya N. Bespalova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953
SPIN-code: 4732-8089

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 3. Histological structure of the liver: a, small to medium vacuolar degeneration of hepatocytes (hematoxylin and eosin staining, zoom ×200); b, moderate venous ectasia with perivascular edema (hematoxylin and eosin staining, zoom ×100)

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3. Fig. 4. Histological structure of the liver: a, medium to large vacuolar degeneration of hepatocytes (hematoxylin and eosin staining, zoom ×100); b, structure of the hepatic beam area is preserved, with ectasia and anemia of the hepatic vein of the triad (hematoxylin and eosin staining, zoom ×200)

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4. Fig. 5. Histological structure of the liver: a, structure of the hepatic beam area is preserved (hematoxylin and eosin staining, zoom ×100); b, foci of large vacuolar degeneration of hepatocytes (hematoxylin and eosin staining, zoom ×200)

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5. Fig. 1. Blood chemistry parameters in rats with non-alcoholic fatty liver disease. 1: non-pregnant rats; 2: pregnant rats without treatment; 3: pregnant rats with treatment

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6. Fig. 2. Enzyme levels in rats with non-alcoholic fatty liver disease. 1: non-pregnant rats; 2: pregnant rats without treatment; 3: pregnant rats with treatment

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