Characteristics of the model of early stage fibrosis in chronic alcoholic liver disease in rats
- Authors: Sivak K.V.1, Savateeva-Lyubimova T.N.2, Stosman K.I.2,3, Kalinina E.Y.2,4
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Affiliations:
- Smorodintsev Research Institute of Influenza, Saint Petersburg, Russia
- Smorodintsev Research Institute of Influenza
- Institute of Toxicology of Federal Medico-Biological Agency
- Saint Petersburg State Pediatric Medical University
- Section: Original research
- Published: 11.12.2024
- URL: https://journals.eco-vector.com/MAJ/article/view/642238
- DOI: https://doi.org/10.17816/MAJ642238
- ID: 642238
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Abstract
Background. The initial stage of liver fibrosis of alcoholic and drug genesis in humans is difficult to diagnose, since it is often asymptomatic. The development of experimental models of early stages of liver fibrosis, close to clinical indicators, allowing to evaluate the effectiveness of candidate hepatoprotectors for the prevention and treatment of fibrosis is an important task of hepatology.
Objective. Development of a model of the initial stage of liver fibrosis with an assessment of typical pathomorphological and biochemical indicators of chronic alcoholic liver disease in rats.
Materials and methods. The experiments were performed on 20 white outbred male rats weighing 270-315 g, which were divided into 2 groups: experimental and control (n = 10 in each group). Alcoholic liver disease was modeled by intragastric administration of 40% ethanol at a dose of 5 g / kg during the first 14 days and at a dose of 3.75 g / kg during the next 14 days. During the experiment, the general condition of the animals, body weight, and mortality were recorded. After the end of the ethanol administration, the animals were subjected to planned euthanasia, blood was taken for biochemical analysis, the liver was taken to determine the concentration of S-adenosylmethionine and histological examination. The severity of liver fibrosis was assessed using the METAVIR scale. In addition, the liver mass coefficient was determined.
Results. The modeled alcoholic liver disease (ALD) was characterized by the presence of mortality, neurological disorders in the form of increased aggression, slow dynamics of body weight gain compared to the control rats. The death of animals from the experimental group (2 rats died) was recorded on the 13th day after the start of ethanol administration. Laboratory data demonstrated elevated levels of aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase activity in the blood, as well as decreased R-Factor and S-adenosylmethionine synthesis in the liver. Liver dysfunction occurred against the background of a decrease in its mass coefficient, nucleomegalic and fatty changes of hepatocytes and moderate hepatofibrosis (stage F2 of METAVIR scale) due to the proliferation of collagen fibers around the bile ducts in the portal tracts and the onset of portoportal septa formation.
Conclusion. The study revealed that the manifestation of typical signs of alcoholic liver disease allows us to recommend this model of ALD for studying the pathogenesis and initial stages of liver cirrhosis, searching for and evaluating the effectiveness of candidate hepatoprotectors and antifibrotic agents.
Key words: ethanol, rats, alcoholic liver disease, liver fibrosis.
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About the authors
Konstantin Vladimirovich Sivak
Smorodintsev Research Institute of Influenza, Saint Petersburg, Russia
Email: kvsivak@gmail.com
ORCID iD: 0000-0003-4064-5033
DS/PhD in Biology, Head of the department of preclinical trials of Smorodintsev Research Institute of Influenza
Russian FederationTatiana N. Savateeva-Lyubimova
Smorodintsev Research Institute of Influenza
Email: drugs_safety@mail.ru
ORCID iD: 0000-0003-4516-3308
Professor, MD, PhD in Medicine, leading researcher in the Laboratory of Drug Safety
Russian Federation, Saint PetersburgKira I. Stosman
Smorodintsev Research Institute of Influenza; Institute of Toxicology of Federal Medico-Biological Agency
Email: labtox6@rambler.ru
ORCID iD: 0000-0001-7959-2376
PhD in Biology, senior researcher in the Laboratory of Drug Safety
Russian Federation, Saint PetersburgElena Yu. Kalinina
Smorodintsev Research Institute of Influenza; Saint Petersburg State Pediatric Medical University
Author for correspondence.
Email: drkalinina@yandex.ru
ORCID iD: 0000-0001-7077-3584
MD, PhD in Medicine (pathologist), Leading Researcher in Laboratory of Drug Safety; Associate Professor, Department of Pathological Anatomy
Saint PetersburgReferences
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