The creation of universally effective and safe correctors of biliary secretion disorders is becoming more timely. There is an urgent need for scientists to find drugs that would correct blood cholesterol levels and metabolism in liver effectively and without limiting side effects. The purpose of the study was to investigate the possibility of using corvitin to correct stress-induced biliary disorders of the liver of male rats. Materials and methods. The article looks at recent research dealing with changes in the bile acid composition of outbred male rats’ bile under chronic social stress (social defeat in daily male confrontations, 14 days) when using Corvitin (1 mg/kg, intragastrically, 7 days). Chronic social stress was created by daily agonistic interactions between animals. The state of memory and the level of research activity in the object recognition test (cognitive test) were also studied. The main fractions of conjugated bile acids (taurocholic, taurohenodeoxycholic and taurodeoxycholic, glycocholic, glycochenodeoxycholic and glycodeoxycholic and free ones – cholic, chenodeoxycholic and deoxycholic) were determined by the method of thin layer chromatography of bile. Results and discussion. Chronic social stress leads to a slight increase in the overall activity of the experimental animals, but significantly impairs the processes of recognition and memory. Social stress significantly inhibits the processes that ensure the synthesis, biotransformation and transport of bile acids in the bile. Also, chronic social stress causes changes in bile production, which reduce the solubilization properties of bile and increase the risk of lithogenesis. Conclusion. The use of Corvitin simultaneously with the simulation of experimental social stress normalized the biliary secretory function of the liver, which indicates a high potential for the use of Corvitin as a corrective factor in chronic social stress. Corvitin used by us in the conditions of experimental social stress to some extent corrected the content of bile acids in the liver of male rats, which indicates the ability of this drug to interfere with the metabolism of cholate in liver cells, in the mechanisms of bile acid transport. Correction of stress-induced pathologies of liver bile-secretory function by Corvitin requires further thorough experimental studies

Keywords: liver, bile, cholates, Corvitin, social defeat model

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1. Baraboy VA, Reznikov OG. Fiziologiya, biokhimiya i psykhologiya stresu [Physiology, biochemistry and psychology of stress]. Мonografiya. K; 2013. 314 p. [Ukrainian]
2. Reznikov AG, Limareva АА. Modulation of Puberty Terms and Sexual Behavior of Rats after prenatal Exposure to Methyldopa, Phenibut, and Stress. Int J Physiol Pathophysiol. 2018; 9(1): 27-35. https://doi.org/10.1615/IntJPhysPathophys.v9.i1.40
3. Boyer JL. Bile formation and secretion. J Comparative Physiol. 2013; 3(3): 1035-1078. https://www.ncbi.nlm.nih.gov/pubmed/23897680. Https://www.ncbi.nlm.nih.gov/pmc/articles/4091928. https://doi.org/10.1002/cphy.c120027
4. Jensen MP, Sherlin LH, Askew RL, Fregni F, Witkop G, Gianas A, et al. Effects of non-pharmacological pain treatments on brain states. Clin Neurophysiol. 2016; 124: 2016-2024. https://www.ncbi.nlm.nih.gov/pubmed/23706958. Https://www.ncbi.nlm.nih.gov/pmc/articles/3759647. https://doi.org/10.1016/j.clinph.2013.04.009
5. Silvennoinen R, Quesada H, Kareinen I, Julve J, Kaipiainen L, Gylling H, et al. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice. Physiolog Rep. 2015; 3(5): 12-14. https://www.ncbi.nlm.nih.gov/pubmed/25969465. Https://www.ncbi.nlm.nih.gov/pmc/articles/4463831. https://doi.org/10.14814/phy2.12402
6. Kulyanda OO. Stan antyoksydantnogo zakhystu tvaryn z politravmoyu pislya provedennya kompleksnoyi korektsiyi [The state of antioxidant protection of animals with polytrauma after a comprehensive correction]. Medychna khimiya. 2015; 1(17): 104-106. [Ukrainian]
7. Giudetti AM, Testini M, Vergara D, Priore P, Damiano F, Gallelli CA, et al. Chronic psychosocial defeat differently affects lipid metabolism in liver and white adipose tissue and induces hepatic oxidative stress in mice fed a high-fat diet. FASEB J. 2019; 33(1): 1428-1439. https://www.ncbi.nlm.nih.gov/pubmed/30133327. https://doi.org/10.1096/fj.201801130R
8. Yun-zi L, Wei P, Ji-kuai C, Wen-jun S, Wen-jie Y, Yun-xia W, et al. FoxO1 is a critical regulator of hepatocyte lipid deposition in chronic stress mice. Peer J. 2019; 7: 76-78. https://www.ncbi.nlm.nih.gov/pubmed/31579588. Https://www.ncbi.nlm.nih.gov/pmc/articles/6768057. https://doi.org/10.7717/peerj.7668
9. Ferents NM. Osoblyvosti aktyvnosti transaminaz u krovi ta pechintsi pry eksperymentalniy pnevmoniyi v umovakh immobilizatsiynogo stresu ta vplyv na nykh korvitynu [Features of transamination in blood and participation in experimental pneumonia in the conditions of immobilization stress and influence on them]. Zdobutky klinichnoyi i eksperymentalnoyi medytsyny. 2016; 1: 82-84. [Ukrainian]
10. Sinclair JG, Main CD, Lo GF. Spinal vs. supraspinal actions of morphine on the rat tail-flick reflex. Pain. 1988; 33(3): 357-362. https://doi.org/10.1016/0304-3959(88)90296-5
11. Carlini VP. The object recognition task: a new proposal for the memory performance study. IntechOpen Access Publisher. 2011; 27-43. https://doi.org/10.5772/14667
12. Vovkun TV, Yanchuk PI, Shtanova LY, Vesеlskyу SP, Shalamaу AS. Exocrine function of the liver in rats with exposure to cоrvitin. Fiziologichnyi Zhurnal. 2016; 62(3): 30-38. https://www.ncbi.nlm.nih.gov/pubmed/29569883. https://doi.org/10.15407/fz62.03.030
13. Kudryavtseva N. A sensory contact model for the study of aggressive and submissive behavior in male mice. Aggressive Behavior. 1991; 17(5): 285-291. https://doi.org/10.1002/1098-2337(1991)17:5<285::AID-AB2480170505>3.0.CO;2-P
14. Horid’ko TM, Kosiakova HV, Berdyshev AG, Meged OF, Gudz EA, Onopchenko OV, et al. Antistress effects of n-stearoylethanolamine in rats with chronic social stress. Ukr Biochem J. 2017; 89(4): 68-76. https://doi.org/10.15407/ubj89.04.068
15. Patent 1624322 Ukraine, MPK G01N 33/50, A 1. Sposob opredelenyja zhelchnyyh kyslot v byologycheskyh zhydkostjah [Method for determination of bile acids in biological fluids] / Veselsky SP, Lyashchenko PS, Luk'janenko YA. (UA); zayavnik i vlasnik patentu Kievskiy gosudarstvennyy universitet imeni Tarasa Shevchenko MOZ Ukraine (UA). № 4411066/14; zayavl 25.01.88; opubl 30.01.91. Byul № 4.
16. Bhatia SN, Toner M, Foy BD, Rotem A, O’Neil KM, Tompkins RG, et al. Zonal Liver Cell Heterogeneity: Effects of Oxygen on Metabolic Functions of Hepatocytes. J Cell Eng. 1996; 1: 125-135.
17. Antunes M, Biala G. The novel object recognition memory: neurobiology, test procedure, and its modifications. Cognitive processing. 2012; 13(2): 93-110. https://www.ncbi.nlm.nih.gov/pubmed/22160349. Https://www.ncbi.nlm.nih.gov/pmc/articles/3332351. https://doi.org/10.1007/s10339-011-0430-z
18. Liashevych AM, Tubalceva II, Reshetnik YM, Bondarenko OV, Veselsky SP, Makarchuk MY. Influence of experimental chronic social stress on bile acids content in the bile of male rats. Fiziologichnyi Zhurnal. 2017; 63(4), 24-29. https://doi.org/https://doi.org/10.15407/fz63.04.024