Dynamics of pathomorphological changes in the liver of rats at different stages of experimental alcohol damage
AbstractLiver diseases represent one of the most common problems in gastroenterology. The liver, as the most important organ of metabolism, which plays a major role in anabolic and energy processes, takes part in the adaptive and compensatory reactions of the body under exogenous and endogenous adverse influences. Individual factors play a major role in the development of this disease, one of which is the duration of the effect of alcohol on the body. The duration of alcohol consumption affects the morpho-functional properties of the liver. When alcohol was given to the research animals, hypertrophic changes were seen in the linear dimensions of hepatocytes: in the 12th week of alcoholization, the nuclear area was 1.25 times larger, and the cytoplasmic area of hepatocytes was 1.16 times larger compared with the same indicators in the 6th week of alcoholization. Alcoholic hepatitis is characterized by protein-fatty degeneration, inflammatory lymphocytic infiltration, increase in the area of sinusoids and the size of hepatocytes, and, accordingly, the Vizotto coefficient (1.83 times in the 6th week and 2.10 times in the 12th week of the research). The alcohol consumption is accompanied by increase in the volume of the nucleus and cytoplasm of hepatocytes, decrease in the nuclear-cytoplasmic ratio with increase in pathohistological changes. With the lengthening of the terms of alcoholization, the number of binuclear hepatocytes decreased. Morphometric calculation of the number of fat cells per 100 hepatocytes showed that in the 12th week of the experiment, the number of fatty inclusions increased by 1.42 times, compared with 6 weeks of forced alcoholization. Fatty small- and large-droplet steatosis of hepatocytes was diffuse in nature. The duration of alcoholization also affects the liver vessels. The diameter of the central vein in the 6th week of the experiment was 1.52 times greater than in control rats, and 1.81 times in the 12th week of alcoholization. The bile ducts of rats of the experimental groups were also larger in diameter: by 37% after 6 weeks and 47% after 12 weeks of forced alcoholization. An increase in the area of the sinusoids and the diameter of the central vein indicates an impairment of the blood supply to the liver. The complexity of the structure of the liver and the diversity of its functions necessitate the use of a variety of diagnostic techniques and methodological approaches to assessing its activity in the normal condition, during a pathology. It will be promising to study the structure of the liver at the ultramicroscopic level of the effect of drugs on the treatment of alcoholic liver disease during different periods of alcoholization.
Antonenko, P. P., Zazharskyi, V. V., Suslova, N. I., Sklyarov, P. M., Reshetnichenko, O. P., Kostyuk, V. K., & Mylostyvyi, R. V. (2020). Efficacy of herbal essential oils at tetrachloromethane induced hepatitis in laboratory rats. World of Medicine and Biology, 16(73), 149–153.
Argemi, J., Ventura-Cots, M., Rachakonda, V., & Bataller, R. (2020). Alcoholic-related liver disease: pathogenesis, management and future therapeutic developments. Revista Española de Enfermedades Digestivas, 112(11), 869–878.
Arteel, G. E. (2020). Liver-lung axes in alcohol-related liver disease. Clinical and Molecular Hepatology, 26(4), 670–676.
Askgaard, G., Kraglund, F., Kann, A. E., Vilstrup, H., & Jepsen, P. (2021). Epidemiology for alcohol-related liver disease. Ugeskrift for Laeger, 183(14), 1–9.
Bajaj, J. S. (2019). Alcohol, liver disease and the gut microbiota. Nature Reviews Gastroenterology and Hepatology, 16(4), 235–246.
Birková, A., Hubková, B., Čižmárová, B., & Bolerázska, B. (2021). Current view on the mechanisms of alcohol-mediated toxicity. International Journal of Molecular Sciences, 22(18), 14–22.
Brygadyrenko, V. V., Lieshchova, M. A., Bilan, M. V., Tishkina, N. M., & Horchanok, A. V. (2019). Effect of alcohol tincture of Aralia elata on the organism of rats and their gut microbiota against the background of excessive fat diet. Regulatory Mechanisms in Biosystems, 10(4), 497–506.
Buchanan, R., & Sinclair, J. M. A. (2021). Alcohol use disorder and the liver. Addiction, 116(5), 1270–1278.
Dastidar, S. G., Warner, J. B., Warner, D. R., McClain, C. J., & Kirpich, I. A. (2018). Rodent models of alcoholic liver disease: Role of binge ethanol administration. Biomolecules, 8(1), 3–21.
Donne, R., Sangouard, F., Celton-Morizur, S., & Desdouets, C. (2021). Hepatocyte polyploidy: Driver or gatekeeper of chronic liver diseases. Cancers, 13(20), 5151.
Elgendy, S. A., Baloza, S. H., Mohammed, L. A., Nasr, H. E., El-Shaer, N. O., Ghamry, H. I., Althobaiti, S. A., Shukry, M., Soliman, M. M., & Elnoury, H. A. (2022). Ameliorative impacts of wheat germ oil against ethanol-induced hepatic and renal dysfunction in rats: Involvement of anti-inflammatory, anti-apoptotic, and antioxidant signaling pathways. Life, 12(10), 1671.
Furuya, S., Cichocki, J. A., Konganti, K., Dreval, K., Uehara, T., Katou, Y., Fukushima, H., Kono, H., Pogribny, I. P., Argemi, J., Bataller, R., & Rusyn, I. (2019). Histopathological and molecular signatures of a mouse model of acute-on-chronic alcoholic liver injury demonstrate concordance with human alcoholic hepatitis. Toxicological Sciences, 170(2), 427–437.
Gao, B., & Bataller, R. (2011). Alcoholic liver disease: Pathogenesis and new therapeutic targets. Gastroenterology, 141(5), 1572–1585.
Ha, Y., Jeong, I., & Hyun, K. Т. (2022). Alcohol-related liver disease: An overview on pathophysiology, diagnosis and therapeutic perspectives. Biomedicines, 10(10), 2530.
Hyun, J., Han, J., Lee, C., Yoon, M., & Jung, Y. (2021). Pathophysiological aspects of alcohol metabolism in the liver. International Journal of Molecular Sciences, 22(11), 5717.
Khaderi, S. A. (2019). Introduction: Alcohol and alcoholism. Clinics in Liver Disease, 23(1), 1–10.
Kong, L.-Z., Chandimali, N., Han, Y.-H., & Kwon, T. (2019). Pathogenesis, early diagnosis, and therapeutic management of alcoholic liver disease. International Journal of Molecular Sciences, 20(11), 2712.
Lamas-Paz, A., Hao, F., Nelson, L. J., Vázquez, M. T., Canals, S., Gómez Del Moral, M., Martínez-Naves, E., & Cubero, F. J. (2018). Alcoholic liver disease: Utility of animal models. World Journal of Gastroenterology, 24(45), 5063–5075.
Lange, C. M., Bechstein, W. O., Berg, T., Engelmann, C., Bruns, T., Canbay, A., Moreau, R., & Trebicka, J. (2018). Acute-on-chronic liver failure. Visceral Medicine, 34(4), 296–300.
Li, W., Li, L., & Hui, L. (2020). Cell plasticity in liver regeneration. Trends in Cell Biology, 30(4), 329–338.
Liu, S.-Y., Tsai, I.-T., & Hsu, Y.-C. (2021). Alcohol-related liver disease: Basic mechanisms and clinical perspectives. International Journal of Molecular Sciences, 22(10), 5170.
Ma, J., Guillot, A., Yang, Z., Mackowiak, B., Hwang, S., Park, O., Peiffer, B. J., Ahmadi, A. R., Melo, L., Kusumanchi, P., Huda, N., Saxena, R., He, Y., Guan, Y., Feng, D., Sancho-Bru, P., Zang, M., MacGregor, C. A., Bataller, R., Tacke, F., Sun, Z., Liangpunsakul, S., & Gao, B. (2022). Distinct histopathological phenotypes of severe alcoholic hepatitis suggest different mechanisms driving liver injury and failure. Journal of Clinical Investigation, 132(14), e157780.
Macdonald, S., Andreola, F., Bachtiger, P., Amoros, A., Pavesi, M., Mookerjee, R., Zheng, Y. B., Gronbaek, H. L., Gerbes, A. L., Sola, E., Caraceni, P., Moreau, R., Gines, P., Arroyo, V., & Jalan, R. (2018). Cell death markers in patients with cirrhosis and acute decompensation. Hepatology, 67(3), 989–1002.
Mihm, S. (2018). Danger-associated molecular patterns (DAMPs): Molecular triggers for sterile inflammation in the liver. International Journal of Molecular Sciences, 19(10), 3104.
Monnig, M. A. (2017). Immune activation and neuroinflammation in alcohol use and HIV infection: Evidence for shared mechanisms. The American Journal of Drug and Alcohol Abuse, 43(1), 7–23.
Okamura, Y., Omori, А., Asada, N., & Ono, А. (2018). Effects of vitamin C and E on toxic action of alcohol on partial hepatectomy-induced liver regeneration in rats. Journal of Clinical Biochemistry and Nutrition, 63(1), 50–57.
Park, S. H., Lee, Y. S., Sim, J., Seo, S., & Seo, W. (2022). Alcoholic liver disease: A new insight into the pathogenesis of liver disease. Archives of Pharmacal Research, 45(7), 447–459.
Seitz, H. K., Bataller, R., Cortez-Pinto, H., Gao, B., Gual, A., Lakner, C., Mathurin, P., Mueller, S., Szabo, G., & Tsukamoto, H. (2018). Alcoholic liver disease. Nature Reviews Disease Primers, 16(4), 16.
Singal, А. K., Bataller, R., Ahn, J., Kamath, P. S., & Shah, V. Н. (2018). ACG clinical guideline: Alcoholic liver disease. World Journal of Gastroenterology, 113(2), 175–194.
Slevin, E., Baiocchi, L., Wu, N., Ekser, B., Sato, K., Lin, E., Ceci, L., Chen, L., Lorenzo, S. R., Xu, W., Kyritsi, K., Meadows, V., Zhou, T., Kundu, D., Han, Y., Kennedy, L., Glaser, S., Francis, H., Alpini, G., & Meng, F. (2020). Kupffer cells: Inflammation pathways and cell-cell interactions in alcohol-associated liver disease. The American Journal of Pathology, 190(11), 2185–2193.
Teschke, R. (2018). Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): Cascade of events, clinical aspects, and pharmacotherapy options. Expert Opinion on Pharmacotherapy, 19(8), 779–793.
Thomes, P. G., Rasineni, K., Yang, L., Donohue Jr., Т. М., Kubik, J. L., McNiven, М. А., & Casey, С. А. (2019). Ethanol withdrawal mitigates fatty liver by normalizing lipid catabolism. American Journal of Physiology Gastrointestinal and Liver Physiology, 316(4), 509–518.
Tsomaia, K., Patarashvili, L., Karumidze, N., Bebiashvili, I., Azmaipharashvili, E., Modebadze, I., Dzidziguri, D., Sareli, M., Gusev, S., & Kordzaia, D. (2020). Liver structural transformation after partial hepatectomy and repeated partial hepatectomy in rats: A renewed view on liver regeneration. World Journal of Gastroenterology, 26(27), 3899–3916.
Zhang, F., Little, A., & Zhang, H. (2017). Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15. Journal of Leukocyte Biology, 101(4), 1015–1027.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.