The role of oxidants and antioxidative parameters in patients with hepatic encephalopathy


  • Sami Bahcebasi Department of Internal Medicine, Kayseri City Hospital, Turkey
  • Gulden Baskol Department of Biochemistry, Erciyes University, Turkey
  • Mevult Baskol Department of Gastroenterology, Erciyes University, Turkey



Hepatic encephalopathy, Oxidative stress, Xanthine oxidase


Background: Hepatic encephalopathy is a serious neuropsychiatric complication of cirrhosis. Changes in the oxidative and anti-oxidative system and nitric oxide levels in brain tissue contribute to the development of symptoms related to HE and HE. Purpose of the study to reveal the alterations in oxidative, anti-oxidative system and nitric oxide levels in cirrhotic patients during and after hepatic encephalopathy periods.

Methods: This was a randomized controlled double-blind study conducted in Erciyes University Hospital between 3 July 2010 and 30 March 2011. We investigated the oxidative and anti-oxidative stress parameters by quantification of total antioxidant capacity (TAC), total oxidant capacity (TOC), nitric oxide (NO), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total thiol and xanthine oxidase (XO) levels in serum. We compared the group of patients with hepatic encephalopathy, post-hepatic encephalopathy (clinically recovered) and control groups (healthy control).  

Results: Thirty hepatic encephalopathy patients were studied. Serum levels of nitric oxide and xanthine oxidase were statistically significantly high in the hepatic encephalopathy group according to control group (p<0.031, and p<0.001, respectively). Serum thiol levels were significantly low in hepatic encephalopathy patients than the controls (p<0.001). Total oxidant capacity, total antioxidant capacity, glutathione peroxidase and superoxide dismutase levels were not significantly different in hepatic encephalopathy group than the controls. Serum thiol levels were low and serum NO levels were high in recovered clinically from hepatic encephalopathy group according to control group currently (p<0.001, p<0.001, respectively). Total antioxidant capacity, total oxidant capacity, glutathione peroxidase, superoxide dismutase and xanthine oxidase levels were similar in both groups (p>0.05). Total antioxidant capacity and especially xanthine oxidase levels were significantly decreased in recovered clinically from hepatic encephalopathy group compared to hepatic encephalopathy group (p<0.05, p<0.001, respectively).

Conclusions: Oxidative system, in   systemic circulation, is activated during hepatic encephalopathy and changes in XO level during and after hepatic encephalopathy is very different. This parameter may be a potential marker in differential diagnosis of hepatic encephalopathy from other coma causes. Further investigation is needed.


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Ramos JF, Rodríguez LC. Review of the final report of the 1998 Working Party on definition, nomenclature and diagnosis of hepatic encephalopathy. Ann Hepatol. 2011;10(2):36-9.

Shawcross DL, Shabbir SS, Taylor NJ, Hughes RD. Ammonia and the neutrophil in the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology. 2010;51(3):1062-9.

Muriel P. Role of free radicals in liver diseases. Hepatol Int. 2009;3:526-36.

Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans. 2007;35(5):1147-50.

Sanchez R, Rose CF. Pathogenesis of Hepatic Encephalopathy in Chronic Liver Disease. J Clin Exp Hepatol. 2018;8(3):262-71.

Schliess F, Gorg B, Haussinger D. Pathogenetic interplay between osmotic and oxidative stress: the hepatic encephalopathy paradigm. Biol Chem. 2006;387(10-11):1363-70.

Murthy CR, Rama Rao KV, Bai G, Norenberg MD. Ammonia induced production of free radicals in primary cultures of rat astrocytes. J Neurosci Res. 2001;66:282-8.

Schliess F, Gorg B, Fischer R, Desjardins P, Bidmon HJ, Herrmann A, et al. Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes. FASEB J. 2002;16(7):739-41.

Kruczek C, Gorg B, Keitel V, Bidmon HJ, Schliess F, Haussinger D. Ammonia increases nitric oxide, free Zn(2+), and metallothionein mRNA expression in cultured rat astrocytes. Biol Chem. 2011;392(12):1155-65.

Widmer R, Kaiser B, Engels M, Jung T, Grune T. Hyperammonemia causes protein oxidation and enhanced proteasomal activity in response to mitochondria-mediated oxidative stress in rat primary astrocytes. Arch Biochem Biophys. 2007;464(1):1-11.

Gorg B, Qvartskhava N, Bidmon HJ, Palomero GN, Kircheis G, Zilles K, et al. Oxidative stress markers in the brain of patients with cirrhosis and hepatic encephalopathy. Hepatology. 2010;52(1):256-65.

Mousa N, Razik A, Zaher A, Hamed M, Shiha G, Effat N, Elbaz S, et al. The role of antioxidants and zinc in minimal hepatic encephalopathy: a randomized trial. Therap Adv Gastroenterol. 2016;9(5):684-91.

Bemeur C, Desjardins P, Butterworth RF. Evidence for oxidative/nitrosative stress in the pathogenesis of hepatic encephalopathy. Metab Brain Dis. 2010;25(1):3-9.

Gorg B, Qvartskhava N, Bidmon HJ, Palomero GN, Kircheis G, Zilles K, et al. Oxidative stress markers in the brain of patients with cirrhosis and hepatic encephalopathy. Hepatology. 2010;52(1):256-65.

Kosenko E, Venediktova N, Kaminsky Y, Montoliu C, Felipo V. Sources of oxygen radicals in brain in acute ammonia intoxication in vivo. Brain Res. 2003;981(1):193-200.

Hilgier W, Anderzhanova E, Oja SS, Saransaari P, Albrecht J. Taurine reduces ammonia- and N-methyl-D-aspartate-induced accumulation of cyclic GMP and hydroxyl radicals in microdialysates of the rat striatum. Eur J Pharmacol. 2003;468(1):21-5.

Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy--definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35(3):716-21.

Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38(12):1103-11.

Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem. 1982;126(1):131-8.

Prajda N, Weber G. Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas. FEBS Lett. 1975;59(2):245-9.

Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37(4):277-85.

Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158-69.

Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497-500.

Hu ML, Louie S, Cross CE, Motchnik P, Halliwell B. Antioxidant protection against hypochlorous acid in human plasma. J Lab Clin Med. 1993;121(2):257-62.

Haussinger D. Hepatic encephalopathy. Acta Gastroenterol Belg. 2010;73(4):457-64.

Tarpey MM, Wink DA, Grisham MB. Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. Am J Physiol Regul Integr Comp Physiol. 2004;286(3):431-44.

Muriel P. Role of free radicals in liver diseases. Hepatol Int. 2009;3:526-36.

Glantzounis GK, Yang W, Koti RS, Mikhailidis DP, Seifalian AM, Davidson BR. The role of thiols in liver ischemia-reperfusion injury. Curr Pharm Des. 2006;12(23):2891-901.

Andersson A, Lindgren A, Arnadottir M, Prytz H, Hultberg B. Thiols as a measure of plasma redox status in healthy subjects and in patients with renal or liver failure. Clin Chem. 1999;45(7):1084-6.

Frei B, Stocker R, Ames BN. Molecular biology of free radical scavenging systems. 1st ed. New York, NY: Cold Spring Harbor Laboratory; 1992: 23-45.

Saugstad OD. Role of xanthine oxidase and its inhibitor in hypoxia: reoxygenation injury. Pediatrics. 1996;98(1):103-7.

Hearse DJ, Manning AS, Downey JM, Yellon DM. Xanthine oxidase: a critical mediator of myocardial injury during ischemia and reperfusion?. Acta Physiol Scand Suppl. 1986;548:65-78.

Xia Y, Zweier JL. Substrate control of free radical generation from xanthine oxidase in the postischemic heart. J Biol Chem. 1995;270(32):18797-803.

Shah VH, Kamath PS. Portal hypertension and gastrointestinal bleeding. In: Feldman M, Frieadman LS, Brandt LJ, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. Philadelphia, PA: Saunders Elsevier; 2010: 1489-1516.






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