Abstract
Purpose
Acute liver failure (ALF) is characterized by a rapid and massive destruction of hepatocytes. The role of oxidative stress in perpetuating the injury is undefined and may be a potential therapeutic target. Our aim was to study serial variation in oxidative stress and antioxidant status in patients with ALF.
Methods
The study involved a prospective case–control study set in a tertiary care referral center. Thirty-two consecutive patients admitted with ALF were included with 23 healthy controls for comparison. Level of systemic oxidative stress as defined by superoxide dismutase (SOD), lipid peroxidation products (thiobarbituric acid reactive derivatives [TBARS]), and the total antioxidant capacity as the ferric reducing ability of plasma (FRAP) was measured at baseline on days 3 and 7.
Results
The patients were aged 24 years (range 13–60 years) and included 20 females. Thirteen (40.6%) patients died. Patients with ALF had significantly increased systemic oxidative stress at presentation, as reflected by higher levels of SOD (P < 0.001) and TBARS (P < 0.001) than controls. Both TBARS levels and FRAP decreased progressively from admission to the end of first week among the survivors (P = 0.004 and 0.015, respectively). The antioxidant status reflected by FRAP (P = 0.001) was significantly lower in ALF patients than controls. No relation was found between the level of oxidative stress and the mortality or complications.
Conclusion
A high level of systemic oxidative stress exists in ALF, with depletion of antioxidant reserves. Further studies are needed to define the clinical correlation of the large pro-oxidant burden.
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References
Trey C, Davidson CS. The management of fulminant hepatic failure. In Popper H, Schaffner F, editors. Progress in Liver Diseases, vol. III. New York: Grune & Stratton; 1970. 282–298.
Fagan EA, Williams R. Fulminant viral hepatitis. Br Med Bull 1990;46:462–480.
Fagan E, Yousef G, Brahm J, Garelick H, Mann G, Wolstenholme A, et al. Persistence of hepatitis A virus in fulminant hepatitis and after liver transplantation. J Med Virol 1990;30:131–136. doi:10.1002/jmv.1890300210.
Ruprah M, Mant TGK, Flanagan RJ. Acute carbon tetrachloride poisoning in 19 patients: implications for diagnosis and treatment. Lancet 1985;1:1027–1029. doi:10.1016/S0140-6736(85)91624-1.
Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose: analysis of the National Multicenter Study (1976 to 1985). N Engl J Med 1988;319:1557–1562.
Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB. Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Ann Intern Med 1986;104:399–404.
Pawa S, Ali S. Boron ameliorates fulminant hepatic failure by counteracting the changes associated with the oxidative stress. Chem Biol Interact 2006;160:89–98. doi:10.1016/j.cbi.2005.12.002.
Detry O, Gaspar Y, Cheramy-Bien JP, De Roover A, Honoré P, Meurisse M, et al. Oxidative stress in the liver and the brain of rats in fulminant hepatic failure. Transplant Proc 2005;37:2883–2885. doi:10.1016/j.transproceed.2005.05.012.
Shapiro H, Ashkenazi M, Weizman N, Shahmurov M, Aeed H, Bruck R. Curcumin ameliorates acute thioacetamide-induced hepatotoxicity. J Gastroenterol Hepatol 2006;21:358–366. doi:10.1111/j.1440-1746.2005.03984.x.
Ritter C, Reinke A, Andrades M, Martins MR, Rocha J, Menna-Barreto S, et al. Protective effect of N-acetylcysteine and deferoxamine on carbon tetrachloride-induced acute hepatic failure in rats. Crit Care Med 2004;32:2079–2083. doi:10.1097/01.CCM.0000142699.54266.D9.
Dikici I, Mehmetoglu I, Dikici N, Bitirgen M, Kurban S. Investigation of oxidative stress and some antioxidants in patients with acute and chronic viral hepatitis B and the effect of interferon-alpha treatment. Clin Biochem 2005;38:1141–1144. doi:10.1016/j.clinbiochem.2005.10.006.
Swietek K, Juszczyk J. Reduced glutathione concentration in erythrocytes of patients with acute and chronic viral hepatitis. J Viral Hepat 1997;4:139–141.
Lu Y, Cederbaum AI. Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1. Toxicol Sci 2006;89:515–523. doi:10.1093/toxsci/kfj031.
Liu LG, Yan H, Yao P, Zhang W, Zou LJ, Song FF, et al. CYP2E1-dependent hepatotoxicity and oxidative damage after ethanol administration in human primary hepatocytes. World J Gastroenterol 2005;11:4530–4535.
Tandon BN, Bernauau J, O’Grady J, Gupta SD, Krisch RE, Liaw YF, et al. Recommendations of the International Association for the Study of the Liver Subcommittee on nomenclature of acute and subacute liver failure. J Gastroenterol Hepatol 1999;14:403–404. doi:10.1046/j.1440-1746.1999.01905.x.
Bhatia V, Singh R, Acharya SK. Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut 2006;55:98–104. doi:10.1136/gut.2004.061754.
Riegler JL, Lake JR. Fulminant hepatic failure. Med Clin North Am 1993;77:1057–1083.
Bhatia V, Batra Y, Acharya SK. Prophylactic phenytoin does not improve cerebral edema or survival in ALF—a controlled clinical trial. J Hepatol 2004;41:89–96. doi:10.1016/j.jhep.2004.03.017.
Jameel S, Durgapal H, Habibullah CM, Khuroo MS, Panda SK. Enteric non-A non-B hepatitis: epidemics, animal transmission, and hepatitis E virus detection by the polymerase chain reaction. J Med Virol 1992;37:263–270. doi:10.1002/jmv.1890370405.
Nanda SK, Yalchinkaya K, Panigrahi AK, Acharya SK, Jameel S, Panda SK. Etiological role of hepatitis ‘E’ virus in sporadic fulminant hepatitis. J Med Virol 1994;42:133–137. doi:10.1002/jmv.1890420207.
Belch JJF, Bridges AB, Scott N, Chopra M. Oxygen free radicals and congestive heart failure. Br Heart J 1991;65:215–218. doi:10.1136/hrt.65.5.245.
Marklund S, Marklund G. Involvement of superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for SOD. Eur J Biochem 1974;47:469–474. doi:10.1111/j.1432-1033.1974.tb03714.x.
Benzie IFF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 1996;239:70–76. doi:10.1006/abio.1996.0292.
Cipak A, Borovic S, Scukanec-Spoljar M, Kirac I, Zarkovic N. Possible involvement of 4-hydroxynonenal in splenocyte regulated liver regeneration. Biofactors 2005;24:217–226.
Park JE, Yang JH, Yoon SJ, Lee JH, Yang ES, Park JW. Lipid peroxidation mediated cytotoxicity and DNA damage in U937 cells. Biochimie 2002;84:1199–1205. doi:10.1016/S0300-9084(02)00039-1.
Akalin FA, Toklu E, Renda N. Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls. J Clin Periodontol 2005;32:238–243. doi:10.1111/j.1600-051X.2005.00669.x.
Raho G, Cassano N, D’Argento V, Vena GA, Zanotti F. Over-expression of Mn superoxide dismutase as a marker of oxidative stress in lesional skin of chronic idiopathic urticaria. Clin Exp Dermatol 2003;28:318–320. doi:10.1046/j.1365-2230.2003.01264.x.
Broide E, Klinowski E, Koukoulis G, Hadzic N, Portmann B, Baker A, et al. Superoxide dismutase activity in children with chronic liver diseases. J Hepatol 2000;32:188–192. doi:10.1016/S0168-8278(00)80062-8.
Choung BY, Byun SJ, Suh JG, Kim TY. Extracellular superoxide dismutase tissue distribution and the patterns of superoxide dismutase mRNA expression following ultraviolet irradiation on mouse skin. Exp Dermatol 2004;13:691–699. doi:10.1111/j.0906-6705.2004.00209.x.
Jaeschke H, Knight TR, Bajt ML. The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity. Toxicol Lett 2003;144:279–288. doi:10.1016/S0378-4274(03)00239-X.
Madan K, Bhardwaj P, Thareja S, Gupta SD, Saraya A. Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD). J Clin Gastroenterol 2006;40:930–935. doi:10.1097/01.mcg.0000212608.59090.08.
Albano E, Mottaran E, Vidali M, Reale E, Saksena S, Occhino G, et al. Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis. Gut 2005;54:987–993. doi:10.1136/gut.2004.057968.
Perlemuter G, Davit-Spraul A, Cosson C, Conti M, Bigorgne A, Paradis V, et al. Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease. Liver Int 2005;25:946–953. doi:10.1111/j.1478-3231.2005.01126.x.
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Bhatia, V., Bhardwaj, P., Elikkottil, J. et al. A 7-day profile of oxidative stress and antioxidant status in patients with acute liver failure. Hepatol Int 2, 465–470 (2008). https://doi.org/10.1007/s12072-008-9098-6
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DOI: https://doi.org/10.1007/s12072-008-9098-6