PDF (Українська)


liver cirrhosis, oxidative stress, antioxidants, prooxidants, comorbid lesions

How to Cite

M. O. Abrahamovych, O. O. Abrahamovych, O. P. Fayura, & L. R. Fayura. (2020). REDOX-HOMEOSTASIS FEATURES IN PATIENTS WITH LIVER CIRRHOSIS DEPENDING ON SEVERITY OF THE INTERNAL ORGANS SYNTROPIC COMORBID LESIONS. Eastern Ukrainian Medical Journal, 8(1), 24-33.;8(1):24-33


Relevance and purpose. Oxidative stress, as an imbalance in the anti-/prooxidants system, is a direct cause or one of the most important pathogenetic links of many diseases. Liver cirrhosis is not an exception. With its decompensation the syntropic comorbid lesions that worsen prognosis and often cause the death of patients of working age occur. However, despite the prevalence of studying the pathogenetic mechanisms of liver cirrhosis, the relationship between the content of pro- and antioxidants in the blood and the presence of comorbidities in different C. H. Child – R. N. Pugh classes is still insufficiently studied. Therefore, the aim of the study is to identify the redox homeostasis features in patients with liver cirrhosis depending on the internal organs syntropic comorbid lesions severity.

Materials and methods. The study was conducted in two stages. 75 patients (23 females (30.7%), 52 males (68.3%) (mean age – 47.2 ± 10.4 years) were included in the randomized trial with the preliminary stratification by the presence of liver cirrhosis. All of them were hospitalized and treated at the Department of Internal Medicine 1 at Danylo Halytsky Lviv National Medical University and the Gastroenterology Department of Lviv Regional Clinical Hospital – Lviv Regional Hepatology Center. All patients underwent the complex comprehensive clinical laboratory and instrumental examination of all organs and systems in accordance with the requirements of the modern medicine. To study the redox homeostasis state the contents of catalase and thiobarbituric acid products, in particular malondialdehyde, were determined. At the first stage, we determined the levels of malondialdehyde and catalase in the cirrhotic patients and syntropic comorbid lesions of the internal organs. According to the second stage we studied the dependence between the characteristic parameters of redox homeostasis changes and the severity of syntropic comorbidities in the cirrhotic patients using the correlation analysis. The actual material was handled on a personal computer in Excel 2010, Statistica 6.0, RStudio v. 1.1.442 and R Commander v.2.4-4 using descriptive statistics. The results obtained in the case of normal distribution were presented as M ± σ, where n is the number of patients examined in the group, in case of abnormal distribution – Me [25,0%; 75.0%]. The difference was considered statistically significant if p < 0.05.

Results. In accordance with the first stage of the study, it was found that the malondialdehyde content was highest in patients with liver cirrhosis and varicose veins of the esophagus (VVE) of 3 degree, cirrhotic gastropathy (CGP) of 3 degree, varicose hemorrhoid veins (VHV) of 2 degree, cirrhotic cardiomyopathy of 3 degree, arterial hypotension of 2 degree, hepatopulmonary syndrome of 3 degree, hepatic encephalopathy (HE) of 3 degree, osteoporosis of 3 degree, anemia of 3 degree. The content of catalase was the lowest in patients with liver cirrhosis and with 3 degree VVE, 3 degree CGP, 3 degree VHV, 3 degree arterial hypotension, 3 degree hepatopulmonary syndrome, 3 degree HE, 2 degree osteoporosis, 2 degree anemia. In accordance with the second stage of the study it was revealed that the severity of VVE, CGP, VHV, cirrhotic cardiomyopathy, hepatopulmonary syndrome of hepatic encephalopathy, osteoporosis significantly increases with malondialdehyde content increasing. In its turn the content of catalase decreases with the VVE, CGP, VHV, cirrhotic cardiomyopathy, arterial hypotension, hepatopulmonary syndrome, osteoporosis severity increase.

Conclusions. Patients with liver cirrhosis have some features of redox homeostasis disorders with increasing of malondialdehyde and decreased of catalase content, depending on the severity of the synthropic comorbid lesions of the internal organs, the correlation of which is most pronounced in the presence of hepatopulmonary syndrome, osteoporosis and cirrhotic cardiomyopathy.;8(1):24-33
PDF (Українська)


1. Schuppan D, Afdhal NH. Liver Cirrhosis. Lancet. 2008;371(9615):838–851. doi: 10.1016/s0140-6736(08)60383-9.
2. Sherlock S: Disorders of the liver and the biliary system. Blackwell: Oxford, 1989. 749 pp.
3. Abrahamovych OO, Abrahamovych MO, Tolopko SYa, Dovhan YP, Ferko MR, Fayura OP. Ultrasound Doppler-flowmetric signes of portal hypertension in patients with liver cirrhosis, complicated with edematous-ascitic syndrome. Gastroenterologia Polska. 2013;20(4):139-142.
4. Parnes E. Ya. Tsyrroz pecheny. Ros. med. zhurnal. 1999;1:45–51.
5. Abrahamovych MO, Abrahamovych OO. Klasyfikatsiia tsyrozu pechinky: retrospektyvnyi pohliad na problemu ta suchasne yii vyrishennia z urakhuvanniam syntropichnykh ko- ta polimorbidnykh urazhen khvoroho. Medytsyna transportu Ukrainy. 2013;2:10-16.
6. Abrahamovych OO, Fayura OP, Abrahamovych UO. Komorbidnist: suchasnyi pohliad na problemu; klacyfikatsiia (povidomlennia druhe). Lvivskyi klinichnyi visnyk. 2016;1:31-39. doi: 10.25040/lkv2016.01.031.
7. Abrahamovych OO, Fayura OP, Abrahamovych UO. Komorbidnist: suchasnyi pohliad na problemu; klacyfikatsiia (povidomlennia pershe). Lvivskyi klinichnyi visnyk. 2015;4:56-64.doi: 10.25040/lkv2015.04.056.
8. Tymyrbulatov RR, Seleznev EY. Metod povyshenyia intensivnosti svobodnoradykalnoho okyslenyia lypydosoderzhashchykh komponentov krovy y eho dyahnostycheskoe znachenye. Lab. delo, 1981;4:209–211.
9. Koroliuk MA, Yvanova LY, Maiorova YH, Tokarev VE. Metod opredelenyia aktyvnosty katalazy. Laboratornoe delo 1983;10:16–18.
10. Vairappan B. Endothelial dysfunction in cirrhosis: Role of inflammation and oxidative stress. World J Hepatol. 2015;7(3):443–459. doi:10.4254/wjh.v7.i3.443.
11. Gracia-Sancho J, Lavina B, Rodriguez-Vilarrupla A, et al. Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability. Hepatology. 2008;47(4):1248–1256. doi:10.1002/hep.22166.
12. Lee JH, Yang ES, Park JW. Inactivation of NADP+-dependent isocitrate dehydrogenase by peroxynitrite. Implications for cytotoxicity and alcohol-induced liver injury. J. Biol. Chem. 2003;278:51360–51371. doi: 10.1074/jbc.m302332200.
13. Ridnour LA, Thomas DD, Mancardi D, Espey MG, Miranda KM, Paolocci N, Feelisch M, Fukuto J, Wink DA. The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen oxide species. Putting perspective on stressful biological situations. Biol. chem. 2004;385:1–10. doi: 10.1515/bc.2004.001.
14. Balasubramaniyan V, Wright G, Sharma V, Davies NA, Sharifi Y, Habtesion A, Mookerjee RP, Jalan R. Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats. Am J Physiol Gastrointest Liver Physiol. 2012;302:G145–G152. doi:10.1152/ajpgi.00097.2011.
15. MacMicking JD, Nathan C, Hom G, Chartrain N, Fletcher DS, Trumbauer M, Stevens K, Xie QW, Sokol K, Hutchinson N. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell. 1995;81:641–650. doi:10.1016/0092-8674(95)90085-3.
16. Guarner C, Soriano G, Tomas A, Bulbena O, Novella MT, Balanzo J, Vilardell F, Mourelle M, Moncada S. Increased serum nitrite and nitrate levels in patients with cirrhosis: relationship to endotoxemia. Hepatology. 1993;18:1139–1143.
17. Morales-Ruiz M, Jimenez W, Perez-Sala D, Ros J, Leivas A, Lamas S, Rivera F, Arroyo V. Increased nitric oxide synthase expression in arterial vessels of cirrhotic rats with ascites. Hepatology. 1996;24:1481–1486. doi:10.1053/jhep.1996.v24.pm0008938184.
18. Garcia-Estan J, Ortiz MC, Lee SS. Nitric oxide and renal and cardiac dysfunction in cirrhosis. Clin. Sci. (Lond). 2002;102:213–222.
19. Zhou WC, Zhang QB, Qiao L. Pathogenesis of liver cirrhosis. World J. Gastroenterol. 2014, 20, 7312–7324. doi:10.3748/wjg.v20.i23.7312.
20. Shim KY, Eom YW, Kim MY, Kang HY, Baik SK. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. Korean J. Intern. Med. 2018;33:453-461. doi:10.3904/kjim.2017.317.
21. Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J. Clin. Invest. 1996;97:1916–1923. doi:10.1172/JCI118623.
22. Yoshiji H, Kuriyama S, Yoshii J, Ikenaka Y, Noguchi R, Nakatani T, Tsujinoue H, Fukui H. Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology. 2001;34:745–750. 10.1053/jhep.2001.28231.
23. Grace JA, Klein S, Herath CB, Granzow M, Schierwagen R, Masing N, Walther T, Sauerbruch T, Burrell LM, Angus PW, et al. Activation of the MAS receptor by angiotensin-(1-7) in the renin-angiotensin system mediates mesenteric vasodilatation in cirrhosis. Gastroenterology. 2013;145:874–884.e5. doi:10.1053/j.gastro.2013.06.036.
24. Pugsley MK. The angiotensin-II (AT-II) receptor blocker olmesartan reduces renal damage in animal models of hypertension and diabetes. Proc. West Pharmacol. Soc. 2005;48:35–38.
25. Jacobs BP, Dennehy C, Ramirez G, Sapp J, Lawrence VA. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. Am. J. Med. 2002;113(6):506-515. doi:10.1016/s0002-9343(02)01244-5.
26. Abrahamovych O, Abrahamovych M, Tolopko S, Fayura O, Ferko M. Character and Frequency of the Variations of Co- and Polymorbid Syntropic Extrahepatic Lesions and Their Dependence on the Hepatopulmonary Syndrome Severity Degree in Cirrhotic Patients. Georgian Medical News. 2016;11 (260):34–41.
27. Shah V, Toruner M, Haddad F, Cadelina G, Papapetropoulos A, Choo K, Sessa WC, Groszmann RJ. Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat. Gastroent. 1999;117(5):1222–1228. doi:10.1016/s0016 5085(99)70408-7.
28. Kwok W, Lee SH, Culberson C, Korneszczuk K, Clemens MG. Caveolin-1 mediates endotoxin inhibition of endothelin-1-induced endothelial nitric oxide synthase activity in liver sinusoidal endothelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2009;297(5):G930–G939. doi:10.1152/ajpgi.00106.2009.
29. Shentu TP, He M, Sun X, Zhang J, Zhang F, Gongol B, Marin TL, Zhang J, Wen L, Wang Y, Geary GG, Zhu Y, Johnson DA, Shyy JY. AMP-Activated Protein Kinase and Sirtuin 1 Coregulation of Cortactin Contributes to Endothelial Function. Arterioscler. Thromb. Vasc. Biol. 2016;36(12):2358–2368. doi:10.1161/ATVBAHA.116.307871.
30. Simões E Silva AC, Miranda AS, Rocha NP, Teixeira AL. Renin angiotensin system in liver diseases: Friend or foe? World J. Gastroenterol. 2017;23(19):3396–3406.
31. Jiang ZY, Zhou QL, Chatterjee A, Feener EP, Myers MG, White MF, King GL. Endothelin-1 modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells. Diabetes. 1999;48:1120–1130.
32. Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic. Biol. Med. 2009;47:469-484.
33. Sessa WC. eNOS at a glance. J. Cell Sci. 2004;117(12):2427–2429.
34. Knapp LT, Klann E. Role of reactive oxygen species in hippocampal long-term potentiation: contributory or inhibitory? J. Neurosci. Res. 2002;70:1–7. doi:10.3748/wjg.v23.i19.3396.
35. Vásquez-Vivar J, Whitsett J, Martásek P, Hogg N, Kalyanaraman B. Reaction of tetrahydrobiopterin with superoxide: EPR-kinetic analysis and characterization of the pteridine radical. Free Radic. Biol. Med. 2001;31:975–985. doi:10.1016/s0891-5849(01)00680-3.
36. Shihata WA, Putra MRA, Chin-Dusting JPF. Is There a Potential Therapeutic Role for Caveolin-1 in Fibrosis? Front. Pharmacol. 2017;567:1-8. doi:10.3389/fphar.2017.00567.
37. Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler. Thromb. Vasc. Biol. 2000; 20:2032–2037. doi:10.1161/01.ATV.20.9.2032.
38. Lluch P, Mauricio MD, Vila JM, Segarra G, Medina P, Del Olmo JA, Rodrigo JM, Serra MA. Accumulation of symmetric dimethylarginine in hepatorenal syndrome. Exp. Biol. Med. (Maywood) 2006;231:70-75. doi:10.1177/153537020623100108.
39. Ginès P, Guevara M, Arroyo V, Rodés J. Hepatorenal syndrome. Lancet. 2003;362:1819-1827. doi:10.1016/ S0140-6736(03)14903-3.
40. Nijveldt RJ, Teerlink T, van Leeuwen PA. The asymmetrical dimethylarginine (ADMA)-multiple organ failure hypothesis. Clin. Nutr. 2003;22:99-104. doi:10.1054/clnu.2002.0614.
41. DeLeve LD. Liver sinusoidal endothelial cells in hepatic fibrosis. Hepatology. 2015;61:1740–1746. doi:10.1002/hep.27376.
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.