Features of the structural and functional parameters of the liver in experimental steatohepatitis and its correction in obese rats
The improvement of the pharmacological strategy of non-alcoholic fatty liver disease is based on the study of the effect of pharmaceutical preparations on the structure and function of the liver. The pathogenesis of steatohepatitis is complex and multifactorial, mainly involving genetic, metabolic and environmental factors. The purpose of the study was to characterize the structural and functional parameters of the liver when using the biologically active compound Angiolin for the correction of experimental steatohepatitis. An experimental study was performed on 110 sexually mature white male rats weighing 180-220 grams, which were kept on a standard diet of vivarium. All animals were divided into two groups: control (30 intact animals) and experimental (80 animals). A model of non-alcoholic steatohepatitis was created for all animals of the experimental group. They were kept on a hypercaloric diet with a high fat and high cholesterol content for 8 weeks. After that, part of the animals (10 rats) was withdrawn from the experiment by intrapleural administration of sodium thiopental (50 mg/kg) and the necessary biochemical and morphological studies were performed. Part of the animals (30 rats) was continued to be kept on a high-fat diet for 4 weeks and the biologically active compound Angiolin was administered (20 rats), and Rings-Locke solutions were administered to 10 rats. After the creation of the model, the other animals of the experimental group (40 rats) were transferred to a full-fledged standard semi-synthetic starch-casein diet, and the biologically active compound Angiolin was administered for 20 rats and Ringer-Locke solution for another 20 rats for 4 weeks. Macroscopic evaluation and description of the liver of animals was carried out after withdrawal under thiopental anesthesia. Statistical analysis of the results was carried out using the program “STATISTICA 8” using parametric and non-parametric methods for assessing the results. It was found that the use of the biologically active compound Angiolin once a day for 30 days can reduce cytolysis syndrome (reduce biochemical parameters such as ALT, AST, gamma-glutamyl transpeptidase), reduce cholestasis syndrome (decrease in alkaline phosphatase level), and normalize liver function, improves the morphological state of hepatocytes, which indicates the normalization of the structural and functional state of the liver.
 Anyanwu, G. O., Onyeneke, E. C., Usunobun, U., & Adegbegi, A. J. (2013). Impact of Anthocleista vogelii root bark ethanolic extract on weight reduction in high carbohydrate diet induced obesity in male wistar rats. African Journal of Biochemistry Research, 7(11), 225-232. doi: 10.5897/AJBR2013.0692
 Arab, J. P., Arrese, M., & Trauner, M. (2018). Recent insights into the pathogenesis of nonalcoholic fatty liver disease. Annual Review of Pathology: Mechanisms of Disease, 13, 321-350. doi: 10.1146 / annurev-pathol-020117-043617.
 Bahrii, M. M., Dibrova, V. A., Popadynets, O. H. & Hryshchuk, M. I. (2016). Methods of morphological studies. Vinnytsia: New Book.
 Belenichev, I. F., Mazur, I. A., Abramov, A. V., Kucherenko, L. I., Bukhtiyarova, N. V., Egorov, A. A., ... & Polyakova, E. N. (2013). The endothelium-protective effect of 3-methyl-1, 2, 4-triazolyl-5-thioacetate (S)-2, 6-diaminohexanic acid (lysinium): Effects on the expression of vascular endothelial growth factor (VEGF) and the characteristics of the endotheliocytes of the cerebral vessels of animals with cerebral ischemia. Neurochemical journal, 7(4), 296-302.
 Benedict, M., & Zhang, X. (2017). Non-alcoholic fatty liver disease: An expanded review. World J. Hepatol., 9(16), 715-732. doi: 10.4254/wjh.v9.i16.715
 European Association for the Study of the Liver. (2016). Electronic address eee, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol., 64(6), 1388-1402. doi: 10.1016/j.jhep.2015.11.004
 Fan, J. G., Saibara, T., Chitturi, S., Kim, B. I., Sung, J. J., Chutaputti, A., & Asia-Pacific Working Party for NAFLD. (2007). What are the risk factors and settings for non alcoholic fatty liver disease in Asia-Pacific? Journal of gastroenterology and hepatology, 22(6), 794-800. doi.org/10.1111/j.1440-1746.2007.04952.x
 Hamaguchi, M., Takeda, N., Kojima, T., Ohbora, A., Kato, T., Sarui, H., ... & Takeda, J. (2012). Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome. World journal of gastroenterology: WJG, 18(13), 1508-1516. doi: 10.3748/wjg.v18.i13.1508
 Hyogo, H., Chayama, K., Yamagishi, S. (2014). Nonalcoholic fatty liver disease and cardiovascular disease. Curr. Pharm. Des., 20(14), 2403-2411. doi: 10.2174/13816128113199990476
 Khukhlina, O. S., Antoniv, A. A., Kuzminska, O. B., Mandryk, O. Ye., & Kotsiubiichuk, Z. Ya. (2018). Morphological features of the comorbid course of non-alcoholic steatohepatitis on the background of obesity and secondary arterial hypertension. Morphologia, 12(3), 140-145. doi.org/10.26641/1997-9665.2018.3.140-145
 Kucera, O., & Cervinkova, Z. (2014). Experimental models of non-alcoholic fatty liver disease in rats. World J. Gastroenterol., 20(26), 8364-8376. doi: 10.3748/wjg.v20.i26.8364
 LaBrecque, D. R., Abbas, Z., Anania, F., Ferenci, P., Khan, A. G., Goh, K. L., ... & Ramos, J. F. (2014). World Gastroenterology Organisation global guidelines: Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Journal of clinical gastroenterology, 48(6), 467-473. doi: 10.1097/MCG.0000000000000116
 Lazo, M., Hernaez, R., Bonekamp, S., Kamel, I. R., Brancati, F. L., Guallar, E., & Clark, J. M. (2011). Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. Bmj, 343, d6891. doi: https://doi.org/10.1136/bmj.d6891
 Lonardo, A., Nascimbeni, F., Mantovani, A., & Targher, G. (2018). Hypertension, diabetes, atherosclerosis and NASH: cause or consequence? Journal of hepatology, 68(2), 335-352. doi: 10.1016/j.jhep.2017.09.021
 Lonardo, A., Nascimbeni, F., Maurantonio, M., Marrazzo, A., Rinaldi, L., & Adinolfi, L. E. (2017). Nonalcoholic fatty liver disease: Evolving paradigms. World Journal of gastroenterology, 23(36), 6571-6592. doi: 10.3748/wjg.v23.i36.6571
 Motamed, N., Rabiee, B., Poustchi, H., Dehestani, B., Hemasi, G. R., Khonsari, M. R., ... & Zamani, F. (2017). Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases. Clinics and research in hepatology and gastroenterology, 41(1), 31-38. doi.org/10.1016/j.clinre.2016.07.005
 Nagornaya, E. A., Belenichev, I. F., Gorchakova, N. A., Mazur, I. A., & Chekman, I. S. (2017). Angiolon Influence on the Morphofunctional Characteristics of Rats’ Endotheliocytes in Chronic Cardiac Insufficiency. Ukrainian Journal of Medicine, Biology and Sport, 3(5), 21-25. doi: 10.26693/jmbs02.03.021
 Novelli, E. L. B., Diniz, Y. S., Galhardi, C. M., Ebaid, G. M. X., Rodrigues, H. G., Mani, F., ... & Novelli Filho, J. L. V. B. (2007). Anthropometrical parameters and markers of obesity in rats. Laboratory animals, 41(1), 111-119.
 Peverill, W., Powell, L., & Skoien, R. (2014). Evolving concepts in the pathogenesis of NASH: beyond steatosis and inflammation. International journal of molecular sciences, 15(5), 8591-8638. doi: 10.3390/ijms15058591
 Pivtorak, K. V. (2015). Submicroscopic State of the Liver in the Correction of Steatosis Using the Hepatoprotector of Amino Acid Origin. Bulletin of problems in Biology and Medicine, 3, 2(123), 310-313.
 Pivtorak, K. V. (2015). Submicroscopic changes in experimental hepatic steatosis. Vіsnyk morfologіi, 21(1), 69-72.
 Pivtorak, K. V., Mazur, I. A., & Voloshyn, M. A. (2015). The ultrastructure of endothelial cells of hepatic steatosis in the correction of new biologically active compound Angiolin. Pathology, 12(3), 49-52. doi: http://dx.doi.org/10.14739/2310-1237.2015.3.55587
 Sahini, N., & Borlak, J. (2014). Recent insights into the molecular pathophysiology of lipid droplet formation in hepatocytes. Progress in lipid research, 54, 86-112. doi: 10.1016/j.plipres.2014.02.002
 Smagris, E., BasuRay, S., Li, J., Huang, Y., Ka‐man, V. L., Gromada, J., Cohen, J.C. & Hobbs, H. H. (2015). Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis. Hepatology, 61(1), 108-118. doi: 10.1002/hep.27242
 Stepanov, Yu. M., Gaidar, Yu. A., Didenko, V. I., Oshmianskaia, N. Yu., & Arzhanova, G. Yu. (2016). Morphological differentiation of hepatic steatosis in patients with alcoholic and non-alcoholic hepatitis. Journal of the National Academy of Medical Sciences of Ukraine, 22(3-4), 359-367.
 Tajiri, K., & Shimizu, Y. (2012). Role of NKT cells in the pathogenesis of NAFLD. International journal of hepatology, 2012. doi: 10.1155/2012/850836
 Takahashi, Y., Soejima, Y., & Fukusato, T. (2012). Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J. Gastroenterol., 18(19), 2300-2308. doi: 10.3748/wjg.v18.i19.2300
 Tumansky, V. A., Fen’, S. V., & Tumanskaya, L. M. (2017). Pathomorphological analysis of adverse effects of non-alcoholic and alcoholic steatohepatitis. Morphologia, 11(4), 59-74.
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