Effect of mesenchymal stem cell transplantation on the structural and functional parameters of the liver in acute toxic hepatitis in rats

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Abstract

Acute toxic hepatitis is a serious health problem for the working population. The currently widely used pharmacological preparations with claimed hepatoprotective properties for the treatment of liver diseases have dubious therapeutic efficacy and cannot restore functional and structural changes in the damaged organ. Thus, the search for new methods of treating liver diseases, including toxic etiology, is an urgent task. An experimental study was conducted on 134 nonlinear white outbred rats (3–5 months) weighing 250–390 g. The animals were divided into four groups: group I, control group (n = 15); group II, single intragastric administration of an oil solution of carbon tetrachloride at a dose of 1500 mg/kg (n = 41); group III, single intravenous administration of multipotent mesenchymal stem cells of the mouse (n = 20); group IV, single intragastric administration of an oil solution of carbon tetrachloride at a dose of 1500 mg/kg and subsequent intravenous transplantation of multipotent mesenchymal stem cells of the mouse (2 × 106) (n = 58). On days 1, 3, 5, and 7 of the experiment, blood sampling was performed for biochemical analysis, and organs and tissues were selected for histological and morphometric studies. The transplantation of multipotent mouse mesenchymal stem cells reduced the mortality of animals after exposure to carbon tetrachloride and did not cause acute toxicity. According to a morphometric study, starting from day 3, the introduction of multipotent mouse mesenchymal stem cells led to a statistically significant decrease in the infiltrative processes in the liver tissue. Statistically significant changes in the biochemical composition of the rat blood serum were noted against the transplantation of multipotent mouse mesenchymal stem cells: a decrease in the activities of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma-glutamyltransferase, amylase, creatinine, uric acid, direct and total bilirubin, and cholesterol. The transplantation of multipotent mouse mesenchymal stem cells was found to be an effective method of treating acute toxic hepatitis. The use of multipotent mouse mesenchymal stem cells contributed to an increase in the survival rate of laboratory animals and faster recovery of structural and functional disorders in liver tissue after its acute toxic damage.

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About the authors

Elena G. Trapeznikova

North-Western State Medical University named after I.I. Mechnikov

Author for correspondence.
Email: pishite22@mail.ru
ORCID iD: 0000-0002-9334-4042
SPIN-code: 8588-4013

graduate student

Russian Federation, Saint Petersburg

Viktor V. Shilov

North-Western State Medical University named after I.I. Mechnikov

Email: pishite22@mail.ru
ORCID iD: 0000-0003-3256-2609
SPIN-code: 3541-4782
Scopus Author ID: 7102157390

doctor of medical sciences, professor

Russian Federation, Saint Petersburg

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2. Fig. 1. Dynamics of the levels of bilirubin and its direct fraction in the blood serum of group II and IV rats on days 1, 3, 5, and 7 after exposure to carbon tetrachloride and transplantation of multipotent mouse mesenchymal stem cells: * — p ≤ 0.05 (Mann — Whitney U-test)

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3. Fig. 2. Dynamics of hepatic transaminases (alanine aminotransferase and aspartate aminotransferase) in rat blood serum on days 1, 3, 5, and 7 after exposure to carbon tetrachloride and transplantation of mouse multipotent mesenchymal stem cells;: * —p ≤ 0,05 (U-test Mann — Whitney)

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4. Fig. 3. Dynamics of the morphometric indicators of the pathological processes in rats after exposure to carbon tetrachloride and transplantation of multipotent mouse mesenchymal stem cells: * — p ≤ 0,05 (U-test Mann — Whitney)

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