Effects of ademetionine on behavior and biochemical blood parameters in rats with fatty liver disease
ORIGINAL PAPERS
Abstract
Introduction. Fatty liver disease is a chronic liver disease characterized by the accumulation of lipids in hepatocytes. Non-alcoholic fatty liver disease is a disease in which fatty liver disease occurs in a person who does not abuse alcohol. The drugs, which contains the active ingredient ademetionine, is used to treat liver diseases caused by various factors. Aim of the study — to evaluate the therapeutic effects of parenteral administration on psychomotor activity, biochemical blood parameters, and histological features of liver structure in rats with mixed-genesis fatty liver disease. Materials and methods. The study was conducted on 20 male Wistar rats. Initially, a model of fatty liver was created. All animals were fed food pellets containing 30% (by weight) fructose and drinking water in place of 10% ethyl alcohol (patent no. 2757199) for 30 days. The rats were then divided into two groups. Control animals were sacrificed on day 31. The experimental group received ademetionine parenterally at a dose of 30 mg/day for 21 days. All rats underwent behavioral assessment using the open field method, biochemical analysis of carbohydrate, lipid, and pigment metabolism, and histological analysis of liver tissue on day 31 for the first group and on day 52 for the second group. Results. In the open field test 21 days after treatment, the experimental group of rats demonstrated increased psychomotor activity compared to the control group. Blood biochemistry showed a decrease in total bilirubin by 88.3%, total cholesterol by 30.9%, glucose by 48.3%, and alkaline phosphatase by 83%. Histological examination of rat liver autopsies revealed a reduced severity of inflammation and enhanced liver reparative processes in the experimental group. Conclusion. Ademetionine demonstrates potential value in the treatment of fatty liver disease, has the ability to improve the functional state of the liver, and also causes an increase in the psychomotor activity of animals.
References
1. Брус Т.В., Пюрвеев С.С., Васильева А.В., Забежинский М.М., Кравцова А.А., Пахомова М.А., Утехин В.И. Морфологические изменения печени при жировой дистрофии различной этиологии. Российские биомедицинские исследования. 2021;6(3):21–26. EDN: HHYCJM.
2. Брус Т.В., Васильев А.Г., Трашков А.П., Кравцова А.А., Балашов Л.Д., Пюрвеев С.С. Способ моделирования жировой болезни печени смешанного генеза у крыс. Патент РФ RU 2757199.
3 декабря 2020 г. 3. Брус Т.В., Евграфов В.А. Патофизиология печеночной недостаточности. Педиатр. 2022;13(3):55–64. https://doi.org/10.17816/PED13355-64.
4. Rinella M.E., Neuschwander-Tetri B.A., Siddiqui M.S., Abdelmalek M.F., Caldwell S. et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797–1835. https://doi.org/10.1097/HEP.0000000000000323.
5. Комиссарова М.Ю., Мальцев P.С., Филин А.М., Алимов М.М., Евдокимова H.B., Новикова В.П. Метаболически-ассоциированная жировая болезнь печени у детей: современный взгляд на патогенез, клинические особенности, методы диагностики и лечения. Экспериментальная и клиническая гастроэнтерология. 2024;(9):75–85. https://doi.org/10.31146/1682-8658-ecg-229-9-75-85.
6. Савченко Я.В., Сергиевская З.А., Лопатиева С.О. Неалкогольная жировая дегенерация печени у людей различных возрастных групп: современный взгляд на проблему. University Therapeutic Journal. 2022;4(1):11–21. https://doi.org/10.56871/4338.2022.10.13.002.
7. Васильев А.Г., Власов Т.Д., Галагудза М.М. Патофизиология. Типовые патологические процессы и состояния. СПб.: СПб ГПМУ; 2023. С. 509–511.
8. Loomba R., Sanyal A.J. The global NAFLD epidemic. Nat Rev Gastroenterol Hepatol. 2013;10(11):686–690. https://doi.org/10.1038/nrgastro.2013.171.
9. Byrne C.D., Targher G. NAFLD: a multisystem disease. J Hepatol. 2015;62(1S):S47–64. https://doi.org/10.1016/j.jhep.2014.12.012.
10. Xian Y.X., Weng J.P., Xu F. MAFLD vs. NAFLD: shared features and potential changes in epidemiology, pathophysiology, diagnosis, and pharmacotherapy. Chinese Medical Journal. 2020;134(1):8–19. https://doi.org/10.1097/CM9.0000000000001263.
11. Ahmed A., Wong R.J., Harrison S.A. Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol. 2015;13(12):2062–2070. https://doi.org/10.3748/wjg.14.2474.
12. Lomonsco R., Ortiz-Lopez C., Orsak B., Webb A., Hardies J. et al. Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology. 2012;55(5):1389–1397. https://doi.org/10.1002/hep.25539.
13. Nelson D.L., Cox M.M., Hoskins A.A. Lehninger principles of biochemistry. New York; 2021. 1152 p.
14. Машковский М.Д. Лекарственные средства. М.: Новая Волна; 2012.
15. Балакина М.Е., Дегтярева Е.В., Некрасов М.С., Брус Т.В., Пюрвеев С.С. Воздействие раннего постнатального стресса на психоэмоциональное состояние и развитие склонности к чрезмерному употреблению высокоуглеводной пищи у крыс. Российские биомедицинские исследования. 2021;6(2):27–37. EDN: ABECPH.
16. Полухина А.В., Винницкая Е.В., Сандлер Ю.Г., Хайменова Т.Ю. Адеметионин в лечении неалкогольной жировой болезни печени. Медицинский Совет. 2015;(15):104–111. https://doi.org/10.21518/2079-701X-2017-15-104-111.
17. Manzillo G., Piccinino F., Surrenti C., Frezza M., Giudici G.A., Grazie C. Multicentre Double-Blind Placebo-Controlled Study of Intravenous and Oral S-Adenosyl-L-Methionine (SAMe) in Cholestatic Patients with Liver Disease. Drug Invest. 1992;1,4(4):90–100. https://doi.org/10.1007/BF03258369.
18. Hardy M.L., Coulter I., Morton S.C., Favreau J., Venuturupalli S. et al. S-Adenosyl-L-Methionine for Treatment of Depression, Osteo arthritis, and Liver Disease. Evid Rep Technol Assess (Summ). 2003;(64):1–3.
19. Ильченко Л.Ю. Возможности применения адеметионина у пациентов с неалкогольной жировой болезнью печени. Медицинский Совет. 2016;(5):150–154. https://doi.org/10.21518/2079-701X-2017-15-104-111.
