Mechanisms of ethanol liver damage in rats with different emotionality
Keywordscytokines, transaminase, liver, heart, ethanol, rats
Alcoholic liver disease is associated with liver injury ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. One of the mechanisms of organs damage is cytokines influences. The intensity of injury depends on individual reactivety.
The aim of the study was to evaluate changes in the blood of interleukins in the heart of high- and low-emotional (HE, LE) male rats with ethanol hepatosis, hepatitis, fibrosis and cirrhosis of the liver and to determine the degree of liver and heart damage.
Material and methods of investigation. The experiments were performed on 72 HE and LE outbred male rats aged 4 months ((control 1, glucose 7 days, acute ethanol hepatitis – EH) and 120 HE and LE autbred male rats aged 5.5-6.5 months (control 2, glucose 67 days, ethanol hepatosis – EHs, ethanol fibrosis – EF, ethanol cirrhosis – EC). The emotionality was determined by "open field" method.
Determined in the blood serum Tumor Necrosis Factor Alpha (TNF-α), Interleukin 1 Beta (IL-1β), Interleukin 4 (IL-4), Interleukin 10 (IL-10), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP). All animals underwent histological examination of the liver and heart, right and left ventricles (RV, LV), and ventricular septum (VS) square.
Results. In EH increase IL-1β, IL-10 and decrease TNF-α in LE rats. In EHs, EF and EC were decrease of IL-1β, IL-4 and IL-10 in HE rats and decrease of TNF-α, IL-4 and IL-10 in LE rats. In EH decrease ALT (more in LE), AST (more in HE) and increase AP. In HE rats in EHs, EF and EC decreased ALT, in EC increased AST. AP in HE rats increased in EHs; decreased in EF and EC. In LE rats ALT was increased in EHs, and decreased in EC; AST was increased in EC; AP was increased in EHs. In both groups of animals at ethanol damage of a liver remodeling of heart is observed. The earlier and bigger is observed in HE rats.
Conclusion. The degree of ethanol damage to the liver and heart depends on the emotionality of the animals and the severity of the simulated pathology, which is more pronounced in highly emotional rats. In the mechanisms of ethanol damage of organism of different emotionality rats take plase cytokines changes. In hepatitis increase IL-1β, IL-10 and decrease TNF-α in low emotions rats. In hepatosis, firosis and cirrhosis were decrease of IL-1β, IL-4 and IL-10 in high emotional rats and decrease of TNF-α, IL-4 and IL-10 in low emotional rats.
Leptin downregulates ethanol-induced secretion of proinflammatory cytokines and growth factor / V. Balasubramaniyan, G. Murugaiyan, R. Shukla, R. R. Bhonde, N. Nalini // Cytokine. 2007;37(1):96–100.
A role for interleukin-10 in alcohol-induced liver sensitization to bacterial lipopolysaccharide / D. B. Hill, N. B. D'Souza, E. Y. Lee, R. Burikhanov, I. V. Deaciuc, W. J. S. de Villiers // Alcohol. Clin. Exp. Res. https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Alcohol+Clin+Exp+Res%22%5BTitle+Abbreviation%5Dhttps://pubmed.ncbi.nlm.nih.gov/11821657/2002;26(1):74–82.
An L., Wang X., Cederbaum A. I. Cytokines in alcoholic liver disease // Arch. Toxicol. 2012;86(9):1337–1348.
Molecular mechanisms of neuroimmunoendocrine effects of alcohol / A. N. Ilnitski, N. I. Zhernakoua, L. I. Postnikoua, O. A. Borisov, N. M. Pozdnyakoua // Scientific information. Medicine series. Pharmacy. 2011;4(99),13:5–12. [in Russian].
Tumour Necrosis Factor Microsatellite Haplotypes Are Associated with Chronic Pancreatitis / D. O. ’Reilly, S. Dunlop, K. Sargen, A. Demaine, S. Wilkinson, A. N. Kingsnotrh // J. Pancreas. 2006;7(1):14–26.
Szabo G. Moderate drinking, inflammation, and liver disease // Annals of Epidimiology. 2007;17:49–54.
Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction / C. Aloman, S. Gehring, P. Wintermeyer, N. Kuzushita, J. R. Wands // Gastroenterology. 2007;132 (2):698–708.
Effects of in vitro ethanol on tumor necrosis factor-alpha production by blood obtained from simian immunodeficiency virus-infected rhesus macaques / D. A. Stoltz, S. Nelson, J. K. Kolls, P. Zhang, R. P. Bohm, M. Murphey-Corb, G. J. Bagby // Alcohol. Clin. Exp. Res. – 2002;26(4):527–534.
Differential contributions of C3, C5, and decay-accelerating factor to ethanol-induced fatty liver in mice / M. T. Pritchard, M. R. McMullen, A. B. Stavitsky, J. I. Cohen, F. Lin, Medof M. Edward, L. E. Nagy // Gastroenterology. 2007;132(3):1117–1126.
Razvodovskiy Yu. Ye. Alcoholic cardiomyopathy: the current state of the problem // Healthcare. 2007;4:42–45. [in Russian].
Lukyanova L. V. Study of behavioral reactions with the introduction of caffeine, carbmazepine and their compositions under conditions of formalin edema in rats. Ukrainian biopharmaceutical journal. 2016;42(1): 22–26. [in Russian].
Kostyuk O.A., Denefil O.V., Holovata T.K. Patent № 135341 IPC: G 09 B 23/28; Method for modeling acute ethanol hepatitis in highly emotional and low-emotional male rats. Published on June 25, 2019, Bull. 12/2019. [in Ukrainian].
Kostyuk O.A., Denefil O.V., Holovata T.K. Patent № 135342 IPC: G 09 B 23/28; Method for modeling chronic ethanol hepatosis in highly emotional and low-emotional male rats. Published on June 25, 2019, Bull. 12/2019. [in Ukrainian].
Kostyuk O.A., Denefil O.V., Holovata T.K. Patent № 135948 IPC: G 09 B 23/28; Method of modeling ethanol cirrhosis in highly emotional and low-emotional male rats. Published on July 25, 2019, Bull. 14/2019. [in Ukrainian].
Kostyuk OA, Denefil OV, Holovata TK. Patent № 135949 IPC: G 09 B 23/28; Method of modeling ethanol fibrosis in highly emotional and low-emotional male rats. Published on July 25, 2019, Bull. 14/2019. [in Ukrainian]..
Sennikov S. V., Silkov A, N. Methods for determination of cytokines // Cytokines and inflammation. 2005;4(1):22–27. [in Russian].
ALT Assay Kit Colorimetric (АLТ; EC 2,6,1,2) АLТ GPT (ALAT) IFCCmod.liqui – UV Kinetic method for determination activity of ALT compliant with the recommendations of experts of the International Society of Clinical Chemistry IFCC. HumanGmbH. Max – Planck – Ring 21, D- 65205 Wiesbaden, Germany.
AST Assay Kit Colorimetric (АSТ; EC 2,6,1,1) АSТ GOT (ASAT) IFCCmod.liqui – UV Kinetic method for determination activity of AST compliant with the recommendations of experts of the International Society of Clinical Chemistry IFCC. HumanGmbH. Max – Planck – Ring 21, D- 65205 Wiesbaden, Germany.
Colorimetric test (Orthophosphate monoetherphosphohydrolase) (Optimum activity in the pH range) ЕС 184.108.40.206. (ALKALINE PHOSPHATASE) liquicolor. Human GmbH. Max – Planck – Ring 21, D- 65205 Wiesbaden, Germany.
Lapach S.N., Chubenko A.V., Babich P.N. Statistical methods in biomedical research using Excel. Kyiv: Morion, 2000. 320 с. [in Russian].
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