Features of redox homeostasis in patients with liver cirrhosis (literature review and clinical case description)

  • M.O. Abrahamovych The Danylo Halytsky National Medical University in Lviv
  • O.O. Abrahamovych The Danylo Halytsky National Medical University in Lviv
  • O.P. Fayura The Danylo Halytsky National Medical University in Lviv
  • L.R. Fayura Institute of Cell Biology, National Academy of Sciences of Ukraine
Keywords: cirrhosis, endothelial dysfunction, oxidative stress, antioxidants, portal hypertension


Aim. To review the literature devoted to the study of redox homeostasis in patients with liver cirrhosis, and to describe the clinical case from practice.

Material and Methods. The content analysis, method of systematic and comparative analysis, and bibliosemantic method of studying relevant research concerning the state of redox homeostasis in patients with liver cirrhosis were used. The data was searched in the following research databases: PubMed, Medline, Springer, Google Scholar, Research Gate by keywords: liver cirrhosis, redox homeostasis, endothelial dysfunction, oxidative stress, antioxidants, portal hypertension. As many as 143 English and Ukrainian sources were analyzed. The sources highlighting the features of redox homeostasis in patients with liver cirrhosis were selected. A clinical case is described.

Results and Discussion. The review of the current literature and the description of the clinical case suggest that under the influence of alcohol, hepatitis B and C, medicines, etc., an imbalance occurs in the system of prooxidants-antioxidants, causing multiple molecular and biochemical changes in the liver and nervous system due to changes in L-arginine, nitric oxide, endothelin metabolism, as well as synthesis, activation, and deactivation of cytokines, lipid peroxidation products, adhesion molecules, pro-, anticoagulation factors, and immune complexes, which increases the disease severity. The revealed role of oxidative stress, in turn, urges us to use medicines with antioxidant properties for treatment of patients with liver cirrhosis.

Conclusions. Under the influence of a number of etiologic factors of the liver cirrhosis onset, there is the disturbance of redox homeostasis, which causes endothelial dysfunction and leads to an imbalance of the autonomic nervous system and increases the disease severity, which causes us to use medicines with antioxidant properties in the treatment.


Abrahamovych OO, Abrahamovych MO. Pokaznyky endotelinu-1 plazmy krovi u patsiientiv z dyfuznymy urazhenniamy pechinky. Praktychna medytsyna. 2011. 17, 4. S.99-103 Ukrainian.

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). P. 34-41.

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. - Vol. 20, N 4. - P. 139-142.

Alexander V, Ivanov O, Khomich А, Birke B. Oxidative Stress in Hepatitis C Infection. The Liver. Oxid Stress Diet Antioxidants 2018, 1-13. https://doi.org/10.1016/B978-0-12-803951-9.00001-X

Andreychyn MA, Ryabokon YY. Rol endotelialnoi dysfunktsii v perebihu hepatytu C ta yiyi korektsiia preparatom L-arhininu. Ukrainian Chemotherapy Journal 2012, 3 (26), 8-14. Ukrainian

Assimakopoulos SF, Gogos C, Labropoulou-Karatza C. Could antioxidants be the "magic pill" for cirrhosis-related complications? A pathophysiological appraisal. Med Hypotheses 2011,77,419-423. https://doi.org/10.1016/j.mehy.2011.05.034

Baffy G. Kupffer cells in non-alcoholic fatty liver disease: the emerging view. J. Hepatol. 2009, 51, 212-223. https://doi.org/10.1016/j.jhep.2009.03.008

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. https://doi.org/10.1152/ajpgi.00097.2011

Bauer M, Bauer I, Sonin NV. Functional significance of endothelin B receptors in mediating sinusoidal and extrasinusoidal effects of endothelins in the intact rat liver. Hepatology 2000, 31(4), 937-947. https://doi.org/10.1053/he.2000.5922

Bec N, Gorren AFC B, Schmidt PP, Andersson KK, Lange R. The role of tetrahydrobiopterin in the activation of oxygen by nitric-oxide synthase. J Inorg Biochem 2000, 81, 207-211. https://doi.org/10.1016/S0162-0134(00)00104-5

Bhogal RH, Weston CJ, Curbishley SM, Adams DH, Afford SC. Autophagy: a cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress. Autophagy 2012, 8, 545-558. https://doi.org/10.4161/auto.19012

Bode C, Kugler V, Bode JC. Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol 1987, 4, 8-14. https://doi.org/10.1016/S0168-8278(87)80003-X

Boger RH. The pharmacodynamics of L-arginine. J Nutr 2007, 137, 6, 1650-1655. https://doi.org/10.1093/jn/137.6.1650S

Boueiz A, Hassoun PM. Regulation of endothelial barrier function by reactive oxygen and nitrogen species. Microvasc Res 2009, 77, 26-34. https://doi.org/10.1016/j.mvr.2008.10.005

Boyer TD. Tolvaptan and hyponatremia in a patient with cirrhosis. Hepatology 2010, 51, 699. https://doi.org/10.1002/hep.23522

Bryan NS. Discovery of the nitric oxide signaling pathway and targets for drug development. Frontiers in Bioscience 2009, 14, 1-18. https://doi.org/10.2741/3228

Castells A, Salo J, Planas R, Quer JC, Gines A, Boix J, Gines P, Gassull MA, Teres J, Arroyo V. Impact of shunt surgery for variceal bleeding in the natural history of ascites in cirrhosis: a retrospective study. Hepatology 1994, 20, 584. https://doi.org/10.1002/hep.1840200306

Center SA. Metabolic, antioxidant, nutraceutical, probiotic, and herbal therapies relating to the management of hepatobiliary disorders. Vet Clin N Am Small Anim Pract 2004, 34, 67-172. https://doi.org/10.1016/j.cvsm.2003.09.015

Chatterjee R, Mitra A. An overview of effective therapies and recent advances in biomarkers for chronic liver diseases and associated liver cancer. Int Immunopharmacol 2015, 24, 335-345. https://doi.org/10.1016/j.intimp.2014.12.024

Chen XM, Huang BQ, Splinter PL, Cao H, Zhu G, McNiven MA, LaRusso NF. Cryptosporidium parvum invasion of biliary epithelia requires host cell tyrosine phosphorylation of cortactin via c-Src. Gastroenterology 2003, 125, 216-228. https://doi.org/10.1016/S0016-5085(03)00662-0

Cheng C, van Haperen R, de Waard M, van Damme LC, Tempel D, Hanemaaijer L, van Cappellen GW, Bos J, Slager CJ, Duncker DJ, van der Steen AF, de Crom R, Krams R. Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique. Blood 2005, 106, 3691-3698. https://doi.org/10.1182/blood-2005-06-2326

Chrobot AM, Szaflarska-Szczepanik A, Drewa G. Antioxidant defense in children with chronic viral hepatitis B and C. Med Sci Monit 2000, 6, 713-78.

Cichoz-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol 2014, 20, 8082-8091. https://doi.org/10.3748/wjg.v20.i25.8082

Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb. Vasc Biol 2000, 20, 2032-2037. https://doi.org/10.1161/01.ATV.20.9.2032

Cooper SA, Whaley-Connell A, Habibi J, Wei Y, Lastra G, Manrique C, Stas S, Sowers JR. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am J Physiol Heart Circ Physiol 2007, 293(4), H2009-2023. https://doi.org/10.1152/ajpheart.00522.2007

Cosen-Binker LI, Kapus A. Cortactin: the gray eminence of the cytoskeleton. Physiology (Bethesda) 2006, 21, 352-361. https://doi.org/10.1152/physiol.00012.2006

Czaja AJ. Hepatic inflammation and progressive liver fibrosis in chronic liver disease. World J Gastroenterol 2014, 20, 2515-2532. https://doi.org/10.3748/wjg.v20.i10.2515

Dalle-Donne I, Rossi R, Colombo R, Gustarini D, Milzani A. Biomarkers of oxidative damage in human disease. Clin Chem 2006, 52, 601-623. https://doi.org/10.1373/clinchem.2005.061408

Das KS, Balakrishnan V, Mukherjee S, Vasudevan DM. Evaluation of blood oxidative stress-related parameters in alcoholic liver disease and non-alcoholic fatty liver disease. Scand J Clin Lab Investig 2008, 68, 323-334. https://doi.org/10.1080/00365510701673383

Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxidative stress and toxicity. J Toxicol 2012, 2012, 645460. https://doi.org/10.1155/2012/645460

DeLeve LD. Liver sinusoidal endothelial cells in hepatic fibrosis. Hepatology 2015, 61, 1740-1746. https://doi.org/10.1002/hep.27376

Diesen DL, Kuo PC. Nitric oxide and redox regulation in the liver: Part II. Redox biology in pathologic hepatocytes and implications for intervention. J Surg Res 2011, 167, 96-112. https://doi.org/10.1016/j.jss.2009.10.006

Dinda PK, Leddin DJ, Beck IT. Histamine is involved in ethanol-induced jejunal microvascular injury in rabbits. Gastroenterology 1988, 95, 1227-1233. https://doi.org/10.1016/0016-5085(88)90355-1

Dudek SM, Jacobson JR, Chiang ET, Birukov KG, Wang P, Zhan X, Garcia JG. Pulmonary endothelial cell barrier enhancement by sphingosine 1-phosphate: roles for cortactin and myosin light chain kinase. J Biol Chem 2004, 279, 24692-24700. https://doi.org/10.1074/jbc.M313969200

Duval F, Moreno-Cuevas JE, Gonzalez-Garza MT, Rodriguez-Montalvo C, Cruz-Vega DE. Protective mechanisms of medicinal plants targeting hepatic stellate cell activation and extracellular matrix deposition in liver fibrosis. Chin Med 2014, 9, 27. https://doi.org/10.1186/s13020-014-0027-4

Federico А, Conti V, Russomanno G, Dallio M. A Long-term Treatment with Silybin in Patients with Non-alcoholic Steatohepatitis Stimulates Catalase Activity in Human Endothelial Cells. In Vivo 2017, 31(4), 609-618. https://doi.org/10.21873/invivo.11101

Fujita N, Sugimoto R, Ma N, Tanaka H, Iwasa M, Kobayashi Y, Kawanishi S, Watanabe S, Kaito M, Takei Y. Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. J Viral Hepat 2008, 15(7), 498-507. https://doi.org/10.1111/j.1365-2893.2008.00972.x

Galicia-Moreno M, Rosique-Oramas D, Medina-Avila Z, Alvarez-Torres T, Falcon D, Higuera-de la tijera F, Bejar YL, Cordero-P?rez P, Munoz-Espinosa L, Perez-Hernandez JL, Kershenobich D, Gutierrez-Reyes G. Behavior of Oxidative Stress Markers in Alcoholic Liver Cirrhosis Patients. Oxid Med Cell Longev 2016, 2016, 9370565. https://doi.org/10.1155/2016/9370565

Garcia Ponce A, Citalan Madrid A, Vargas Robles H. Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility. Sci Rep 2016, 6, 29003. https://doi.org/10.1038/srep29003

Garcia-Estan J, Ortiz MC, Lee SS. Nitric oxide and renal and cardiac dysfunction in cirrhosis. Clin Sci (Lond) 2002, 102, 213-222. https://doi.org/10.1042/cs1020213

Garcia-Tsao G. Bacterial translocation: Cause or consequence of decompensation in cirrhosis. J Hepatol 2001, 34, 150-155. https://doi.org/10.1016/S0168-8278(00)00006-4

Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet 2003, 362, 1819-1827. https://doi.org/10.1016/S0140-6736(03)14903-3

Grace JA, Klein S, Herath CB, Granzow M, Schierwagen R, Masing N, Walther T, Sauerbruch T, Burrell LM, Angus PW. Activation of the MAS receptor by angiotensin-(1-7) in the renin-angiotensin system mediates mesenteric vasodilatation in cirrhosis. Gastroenterology 2013, 145, 874-884. https://doi.org/10.1053/j.gastro.2013.06.036

Gracia-Sancho J, Lavina B, Rodriguez-Vilarrupla A. Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability. Hepatology 2008, 47(4), 1248-1256. https://doi.org/10.1002/hep.22166

Gracia-Sancho J, Russo L, Garcia-Caldero H, Garcia-Pagan JC, Garcia-Cardena G, Bosch J. Endothelial expression of transcription factor Kruppel-like factor 2 and its vasoprotective target genes in the normal and cirrhotic rat liver. Gut. 2011, 60(4), 517-524. https://doi.org/10.1136/gut.2010.220913

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. https://doi.org/10.1002/hep.1840180520

Hutcheson IR, Griffith TM. Mechanotransduction through the endothelial cytoskeleton: mediation of flow- but not agonist-induced EDRF release. Br J Pharmacol 1996, 118, 720-726. https://doi.org/10.1111/j.1476-5381.1996.tb15459.x

Iglarz M, Clozel M. Mechanisms of ET-1-induced endothelial dysfunction. J Cardiovasc Pharmacol 2007, 50, 621-628. https://doi.org/10.1097/FJC.0b013e31813c6cc3

Ishikawa T, Seki S. The association between oxidative stress and endothelial dysfunction in early childhood patients with Kawasaki disease. BMC Cardiovasc Disord 2018, 18(1), 30. https://doi.org/10.1186/s12872-018-0765-9

Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. J Hepatol 2007, 46(5), 927-934. https://doi.org/10.1016/j.jhep.2007.02.006

Iwakiri Y. The molecules: mechanisms of arterial vasodilatation observed in the splanchnic and systemic circulation in portal hypertension. J Clin Gastroenterol 2007, 41(10), S288-S294. https://doi.org/10.1097/MCG.0b013e3181468b4c

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. https://doi.org/10.2337/diabetes.48.5.1120

Juan CC, Fang VS, Huang YJ, Kwok CF, Hsu YP, Ho LT. Endothelin-1 induces insulin resistance in conscious rats. Biochem Biophys Res Commun 1996, 227, 694-699. https://doi.org/10.1006/bbrc.1996.1571

Karabulut AB, Gui M, Karabulut E, Kiran TR, Ocak SG, Otlu O. Oxidant and antioxidant activity in rabbit livers treated with zoledronic acid. Transplant Proc 2010, 42, 3820-3822. https://doi.org/10.1016/j.transproceed.2010.06.017

Kansagra C, Kumar A, Abhisheka T, Joshi N, Sukanya B, Sandip S, Nikhil S, Kunal V. NT Pro-BNP Levels in Patients With Cirrhosis: Correlation With Cardiovascular Dysfunction and Severity of Disease. Clinical Gastroenterology and Hepatology 2015, 13(1), 214. https://doi.org/10.1016/j.cgh.2014.09.007

Katerynchuk IP. Sertsevo-sudynnyi kontynuum - vid dysfunktsii endoteliiu do sudynnykh ta pozasudynnykh proiaviv aterosklerozu: zavdannia i mozhlyvosti simeinoho likaria shchodo profilaktyky, diahnostyky ta likuvannia. Praktychna anhiolohiia. 1 (30) 2010. Ukrainian

Kawada N, Tran-Thi TA, Klein H, Decker K. The contraction of hepatic stellate (Ito) cells stimulated with vasoactive substances. Possible involvement of endothelin 1 and nitric oxide in the regulation of the sinusoidal tonus. Eur J Biochem 1993, 213(2), 815-823. https://doi.org/10.1111/j.1432-1033.1993.tb17824.x

Kim CH, Zou YN, Kim DH, Kim ND, Yu BP, Chung HY. Proteomic analysis of nitrated and 4-hydroxy-2-nonenal modified serum proteins during aging. J Gerontol A BiolSci Med Sci 2006, 61, 332-338. https://doi.org/10.1093/gerona/61.4.332

Kwok W, Clemens MG. Targeted mutation of Cav-1 alleviates the effect of endotoxin in the inhibition of ET-1-mediated eNOS activation in the liver. Shock 2010, 33(4), 392-398. https://doi.org/10.1097/SHK.0b013e3181be3e99

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. https://doi.org/10.1152/ajpgi.00106.2009

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. https://doi.org/10.1074/jbc.M302332200

Lee JY. Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, Pandey UB, Kaushik S, Tresse E, Lu J, Taylor JP, Cuervo AM, Yao TP. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J 2010, 29, 969-980. https://doi.org/10.1038/emboj.2009.405

Lee KC, Ying-Ying Y, Ying-Wen W, Lee FY, Loong CC, Hou MG, Lin HC, Lee SD. Increased Plasma Malondialdehyde in Patients with Viral Cirrhosis and Its Relationships to Plasma Nitric Oxide, Endotoxin, and Portal Pressure. Digestive Diseases and Sciences 2009, 55, 2077-2085. https://doi.org/10.1007/s10620-009-0990-2

Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008, 132, 27-42. https://doi.org/10.1016/j.cell.2007.12.018

Li H, Huang MH, Jiang JD, Peng ZG. Hepatitis C: From inflammatory pathogenesis to anti-inflammatory/hepatoprotective therapy. World J Gastroenterol 2018, 24(47), 5297-5311. https://doi.org/10.3748/wjg.v24.i47.5297

Li S, Tan HY, Wang N, Zhang Z-J, Lao L, Wong C-W, Feng Y. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int J Mol Sci 2015, 16(11), 26087-26124. https://doi.org/10.3390/ijms161125942

Li Y, Liu J, Zhan X. AMPK and SIRT1 Coregulation of Cortactin Contributes to Endothelial Function, Tyrosine Phosphorylation of Cortactin Is Required for H2O2-mediated Injury of Human Endothelial Cells. Arterioscler Thromb Vasc Biol 2016, 36(12), 2358-2368.

Li Y, Liu J, Zhan X.Tyrosine phosphorylation of cortactin is required for H2O2-mediated injury of human endothelial cells. J Biol Chem 2000, 24, 275(47), 37187-37193. https://doi.org/10.1074/jbc.M005301200

Licata G, Tuttolomondo A, Licata A, Parrinello G, Di Raimondo D, Di Sciacca R, Camm C, Crax A, Paterna S, Pinto A. Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites. Aliment Pharmacol Ther 2009, 30, 227. https://doi.org/10.1111/j.1365-2036.2009.04040.x

Liu S, Premont RT, Kontos CD, Huang J, Rockey DC. Endothelin-1 activates endothelial cell nitric-oxide synthase via heterotrimeric G-protein betagamma subunit signaling to protein jinase B Akt. J Biol Chem 2003, 278(50), 49929-49935. https://doi.org/10.1074/jbc.M306930200

Liu W, Phang, JM. Proline dehydrogenase (oxidase), a mitochondrial tumor suppressor, and autophagy under the hypoxia microenvironment. Autophagy 2012, 8, 1407-1409. https://doi.org/10.4161/auto.21152

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. https://doi.org/10.1177/153537020623100108

Lluch P, Segarra G, Medina P. Asymmetric dimethylarginine as a mediator of vascular dysfunction in cirrhosis. World J Gastroenterol 2015, 21(32), 9466-9475. https://doi.org/10.3748/wjg.v21.i32.9466

Locatelli F, Del Vecchio L, Cavalli A. Inhibition of the renin-angiotensin system in chronic kidney disease: a critical look to single and dual blockade. Nephron Clin Pract 2009, 113, c286-c293. https://doi.org/10.1159/000235946

Lodder J, Denaes T, Chobert MN, Wan J, El-Benna J, Pawlotsky JM, Lotersztajn S, Teixeira-Clerc F. Macrophage autophagy protects against liver fibrosis in mice. Autophagy 2015, 11, 1280-1292. https://doi.org/10.1080/15548627.2015.1058473

Luo X, Wang D, Luo X, Zhu X, Wang G, Ning Z, Li Y, Ma X, Yang R, Jin S, Huang Y, Meng Y, Li X. Caveolin 1-related autophagy initiated by aldosterone-induced oxidation promotes liver sinusoidal endothelial cells defenestration. Redox Biol 2017, 13, 508-521. https://doi.org/10.1016/j.redox.2017.07.011

Luo X, Wang D, Zhu X, Wang G, You Y, Ning Z, Li Y, Jin S, Huang Y, Hu Y, Chen T, Meng Y, Li X. Autophagic degradation of caveolin-1 promotes liver sinusoidal endothelial cells defenestration. Cell Death Dis 2018, 9, 576. https://doi.org/10.1038/s41419-018-0567-0

Luu AZ, Chowdhury B, Al-Omran M, Teoh H, Hess DA, Verma S. Role of Endothelium in Doxorubicin-Induced Cardiomyopathy. Microcirculation 2018, 25(7), e12486.

MacGrath SM, Koleske AJ. Cortactin in cell migration and cancer at a glance. J Cell Sci 2012, 125(Pt 7), 1621-1626. https://doi.org/10.1242/jcs.093781

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. https://doi.org/10.1016/0092-8674(95)90085-3

Mallikarjuna K, Shanmugam KR, Nishanth K, Wu MC, Hou CW, Kuo CH, Reddy KS. Alcohol-induced deterioration in primary antioxidant and glutathione family enzymes reversed by exercise training in the liver of old rats. Alcohol 2010, 44, 523-529. https://doi.org/10.1016/j.alcohol.2010.07.004

Matei V, Rodriguez-Vilarrupla A, Deulofeu R, Colomer D, Fernandez M, Bosch J, Garcia-Pagan JC. The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis. Hepatology 2006, 44, 44-52. https://doi.org/10.1002/hep.21228

Matei V, Rodriguez-Vilarrupla A, Deulofeu R, Garcia-Caldero H, Fernandez M, Bosch J, Garcia-Pagan JC. Three-day tetrahydrobiopterin therapy increases in vivo hepatic NOS activity and reduces portal pressure in CCl4 cirrhotic rats. J Hepatol 2008, 49, 192-197. https://doi.org/10.1016/j.jhep.2008.04.014

Mittler R. Oxidative stress, antioxidants and stress tolerance. Trends Plant Sci 2002, 7, 405-410. https://doi.org/10.1016/S1360-1385(02)02312-9

Moller S. Circulatory abnormalities in cirrhosis with focus on neurohumoral aspects. Semin Nephrol 1997, 17(6), 505-519.

Moore K. Endothelin and vascular function in liver disease. Gut 2004, 531-559.

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. https://doi.org/10.1002/hep.510240630

Moreau R, Nguyen BT, Doneanu CE, Hagen TM. Reversal by aminoguanidine of the age-related increase in glycoxidation and lipoxidation in the cardiovascular system of Fischer 344 rats. Biochem Pharmacol 2005, 69, 29-40. https://doi.org/10.1016/j.bcp.2004.09.006

Mormone E, George J, Nieto N. Molecular pathogenesis of hepatic fibrosis and current therapeutic approaches. Chem Biol Interact 2011, 193, 225-231. https://doi.org/10.1016/j.cbi.2011.07.001

Nijveldt RJ, Teerlink T, van Leeuwen PA. The asymmetrical dimethylarginine (ADMA)-multiple organ failure hypothesis. Clin Nutr 2003, 22, 99-104. https://doi.org/10.1054/clnu.2002.0614

Niki E. Lipid peroxidation: physiological levels and dual biological effects. Free Radic Biol Med 2009, 47, 469-484. https://doi.org/10.1016/j.freeradbiomed.2009.05.032

N'Kontchou G, Seror O, Bourcier V, Ajavon Y, Castera L, Grando-Lemaire V, Ganne-Carrie N, Sellier N, Trinchet JC, Beaugrand M. Partial splenic embolization in patients with cirrhosis: efficacy, tolerance and long-term outcome in 32 patients. Eur J Gastroenterol Hepatol 2005, 17, 179. https://doi.org/10.1097/00042737-200502000-00008

Osman HG, Gabr OM, Lotfy S, Gabr S. Serum levels of bcl-2 and cellular oxidative stress in patients with viral hepatitis. Indian J Med Microbiol 2007, 25, 323-329. https://doi.org/10.4103/0255-0857.37333

Ou HY, Huang TL, Chen TY, Tsang LL, Concejero AM, Chen CL, Cheng YF. Emergency splenic arterial embolization for massive variceal bleeding in liver recipient with left-sided portal hypertension. Liver Transpl 2005, 11, 1136. https://doi.org/10.1002/lt.20543

Palm F, Onozato ML, Luo Z, Wilcox CS. Dimethylarginine dimethylaminohydrolase (DDAH): Expression, regulation, and function in the cardiovascular and renal systems. Am J Physiol Heart Circ Physiol 2007, 293, H3227-H3245. https://doi.org/10.1152/ajpheart.00998.2007

Palsson B, Hallen M, Forsberg AM, Alwmark A. Partial splenic embolization: long-term outcome. Langenbecks Arch Surg 2003, 387, 421. https://doi.org/10.1007/s00423-002-0342-6

Papadakis MA, Arieff AI. Unpredictability of clinical evaluation of renal function in cirrhosis. Prospective study. Am J Med 1987, 82, 945. https://doi.org/10.1016/0002-9343(87)90156-2

Parnes EY. Tsyrroz pecheny. Ros med zhurnal 1999; 1: 45-51. Russian

Possomato-Vieira JS, Khalil RA. Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia. Adv Pharmacol 2016, 77, 361-431. https://doi.org/10.1016/bs.apha.2016.04.008

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.

Rajagopalan S, Kurz S, Munzel 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. https://doi.org/10.1172/JCI118623

Rasaratnam B, Kaye D, Jennings G, Dudley F, Chin-Dusting J. The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial. Ann Intern Med 2003, 139, 186-193. https://doi.org/10.7326/0003-4819-139-3-200308050-00008

Reeves WB, Andreoli TE. Chapter 31 - Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct. In Seldin and Giebisch's the kidney: physiology and pathophysiology. Eds.: Giebisch GH, Alpern RA, Herbert SC, Seldin DW, Elsevier/Academic Press, Amsterdam: 2008, 849-887. https://doi.org/10.1016/B978-012088488-9.50034-6

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. https://doi.org/10.1515/BC.2004.001

Riordan SM, Skinner N, Nagree A, McCallum H, McIver CJ, Kurtovic J, Hamilton JA, Bengmark S, Williams R, Visvanathan K. Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis. Hepatology 2003, 37, 1154-1164. https://doi.org/10.1053/jhep.2003.50180

Rockey DC. Vasoactive agents in intrahepatic portal hypertension and fibrogenesis: implications for therapy. Gastroenterology 2000, 118, 1261-1265. https://doi.org/10.1016/S0016-5085(00)70379-9

Rosemurgy AS, Goode SE, Zwiebel BR, Black TJ, Brady PG. A prospective trial of transjugular intrahepatic portasystemic stent shunts versus small-diameter prosthetic H-graft portacaval shunts in the treatment of bleeding varices. Ann Surg 1996, 224, 378. https://doi.org/10.1097/00000658-199609000-00014

Runyon BA. Ascites and spontaneous bacterial peritonitis. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease, Pathophysiology/Diagnosis/Management. Eds.: Feldman M, Friedman LS, Sleisenger MH, WB Saunders, Philadelphia 2002, 1517. https://doi.org/10.1016/B978-1-4160-6189-2.00091-3

Runyon BA. Historical aspects of treatment of patients with cirrhosis and ascites. Semin Liver Dis 1997, 17, 163. https://doi.org/10.1055/s-2007-1007195

Sakaguchi S, Takahashi S, Sasaki T, Kumagai T, Nagata K. Progression of alcoholic and non-alcoholic steatohepatitis: Common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet 2011, 26, 30-46. https://doi.org/10.2133/dmpk.DMPK-10-RV-087

Schulze F. L-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides. Nutr Res 2009, 29(5), 291-297. https://doi.org/10.1016/j.nutres.2009.04.004

Schuppan D, Afdhal NH. Liver Cirrhosis. Lancet 2008, 371 (9615), 838-851. https://doi.org/10.1016/S0140-6736(08)60383-9

Searles CD, Ide L, Davis ME, Cai H, Weber M. Actin cytoskeleton organization and posttranscriptional regulation of endothelial nitric oxide synthase during cell growth. Circ Res 2004, 95, 488-495. https://doi.org/10.1161/01.RES.0000138953.21377.80

Sessa WC. eNOS at a glance. J Cell Sci 2004, 117(12), 2427-2429. https://doi.org/10.1242/jcs.01165

Shah R, Mahour GH, Ford EG, Stanley P. Partial splenic embolization. An effective alternative to splenectomy for hypersplenism. Am Surg 1990, 56, 774.

Shah V, Haddad FG, Garcia-Cardena G, Frangos JA, Mennone A, Groszmann RJ, Sessa WC. Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids. J Clin Invest 1997, 100(11), 2923-2930. https://doi.org/10.1172/JCI119842

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. https://doi.org/10.1016/S0016-5085(99)70408-7

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. https://doi.org/10.1161/ATVBAHA.116.307871

Sherlock S: Disorders of the liver and the biliary system. Blackwell, Oxford 1989, 8th ed., 82-86.

Shim KY, Eom YW, Kim MY, Kang SH, Baik SK. Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension. Korean J Intern Med 2018, 33(3), 453-461. https://doi.org/10.3904/kjim.2017.317

Shrestha B, Prasai PK, Kaskas AM, Khanna A, Letchuman V, Letchuman S, Alexander JS, Orr AW, Woolard MD, Pattillo CB. Differential arterial and venous endothelial redox responses to oxidative stress. Microcirculation 2018, 25(7), e12486. https://doi.org/10.1111/micc.12486

Simoes 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. https://doi.org/10.3748/wjg.v23.i19.3396

Singal AK, Jampana SC, Weinman SA. Antioxidants as therapeutic agents for liver disease. Liver Int 2011, 31, 1432-1448. https://doi.org/10.1111/j.1478-3231.2011.02604.x

Siqueira C, de Moura MC, Pedro AJ, Rocha P. Elevated nitric oxide and 3',5' cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis. World J Gastroenterol 2008, 14, 236-242. https://doi.org/10.3748/wjg.14.236

Szczurek W, Szygula-Jurkiewicz B. Oxidative stress and inflammatory markers - the future of heart failure diagnostics? Kardiochir Torakochirurgia Pol 2015, 12(2), 145-149. https://doi.org/10.5114/kitp.2015.52856

Tain YL, Kao YH, Hsieh CS, Chen CC, Sheen JM, Lin IC., Huang LT. Melatonin blocks oxidative stress-induced increased asymmetric dimethylarginine. Free Radic Biol Med 2010, 49, 1088-1098. https://doi.org/10.1016/j.freeradbiomed.2010.06.029

Thabut D, Shah V. Intrahepatic angiogenesis and sinusoidal remodeling in chronic liver disease: new targets for the treatment of portal hypertension? J Hepatol 2010, 53(5), 976-980. https://doi.org/10.1016/j.jhep.2010.07.004

Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet 2014, 383(9930), 1749-1761. https://doi.org/10.1016/S0140-6736(14)60121-5

Vairappan B. Endothelial dysfunction in cirrhosis: Role of inflammation and oxidative stress. World J Hepatol 2015, 7(3), 443-459. https://doi.org/10.4254/wjh.v7.i3.443

Vasquez-Vivar J, Whitsett J, Martasek 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. https://doi.org/10.1016/S0891-5849(01)00680-3

Videla LA, Rodrigo R, Orellana M, Fernandez V, Tapia G, Quinones L, Varela N, Contreras J, Lazarte R, Csendes A. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci 2004, 106, 261-268. https://doi.org/10.1042/CS20030285

Waled A. Shihata, Mohammad R. A. Putra1 and Jaye P. F. Chin-Dusting. Is There a Potential Therapeutic Role for Caveolin-1 in Fibrosis? Front. Pharmacol 2017, 567, 1-8. https://doi.org/10.3389/fphar.2017.00567

Wong F, Watson H, Gerbes A, Vilstrup H, Badalamenti S, Bernardi M, Ginas P; Satavaptan Investigators Group. Satavaptan for the management of ascites in cirrhosis: efficacy and safety across the spectrum of ascites severity. Gut 2012, 61, 108. https://doi.org/10.1136/gutjnl-2011-300157

Wong F. The renal sympathetic and renin-angiotensin response to lower body negative pressure in well-compensated cirrhosis. Gastroenterol 1998, 155(2), 397-405. https://doi.org/10.1016/S0016-5085(98)70206-9

Wong F, Siu S, Liu P, Blendis LM. Brain natriuretic peptide: is it a predictor of cardiomyopathy in cirrhosis? Clin Sci (Lond) 2001, 101(6), 621-628. https://doi.org/10.1042/cs1010621

Wu D, Cederbaum AI. Oxidative stress and alcoholic liver disease. Semin Liver Dis 2009, 29, 141-154. https://doi.org/10.1055/s-0029-1214370

Xu RY, Liu B, Lin N. Therapeutic effects of endoscopic variceal ligation combined with partial splenic embolization for portal hypertension. World J Gastroenterol 2004, 10, 1072. https://doi.org/10.3748/wjg.v10.i7.1072

Xu XM, Zhou XY, Li XY, Guo J, Wang HZ, Li Y, Yang CC, Liu TH, Cai JP. Increased oxidative damage of RNA in liver injury caused by hepatitis B virus (HBV) infection. Free Radic Res 2018, 52(4), 426-433. https://doi.org/10.1080/10715762.2018.1439165

Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988, 332, 411-415. https://doi.org/10.1038/332411a0

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. https://doi.org/10.1053/jhep.2001.28231

Zampino R, Marrone A, Rinaldi L, Guerrera B, Nevola R, Boemio A, Iuliano N, Giordano M, Passariello N, Sasso FC, Albano E, Adinolfi LE. Endotoxinemia contributes to steatosis, insulin resistance and atherosclerosis in chronic hepatitis C: the role of pro-inflammatory cytokines and oxidative stress. Infection 2018, 46(6), 793-799. https://doi.org/10.1007/s15010-018-1185-6

Zhou C, Lai Y, Huang P, Xie L, Lin H, Zhou Z, Mo C, Deng G, Yan W, Gao Z, Huang S, Chen Y, Sun X, Lv Z, Gao L. Naringin attenuates alcoholic liver injury by reducing lipid accumulation and oxidative stress. Life Sci 2019, 216, 305-312. https://doi.org/10.1016/j.lfs.2018.07.031

Zhou WC, Zhang QB, Qiao L. Pathogenesis of liver cirrhosis. World J Gastroenterol 2014, 20, 7312-7324. https://doi.org/10.3748/wjg.v20.i23.7312

How to Cite
Abrahamovych, M., Abrahamovych, O., Fayura, O., & Fayura, L. (2020). Features of redox homeostasis in patients with liver cirrhosis (literature review and clinical case description). Acta Medica Leopoliensia, 26(1), 70-86. https://doi.org/10.25040/aml2020.01.070