Euroasian journal of hepato-gastroenterology

Register      Login

VOLUME 6 , ISSUE 1 ( January-June, 2016 ) > List of Articles


Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease

Makoto Irie, Tetsuro Sohda, Akira Anan, Atsushi Fukunaga, Kazuhide Takata, Takashi Tanaka

Citation Information : Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T. Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease. Euroasian J Hepatogastroenterol 2016; 6 (1):13-18.

DOI: 10.5005/jp-journals-10018-1159

License: CC BY-NC 4.0

Published Online: 01-12-2017

Copyright Statement:  Copyright © 2016; The Author(s).


Background and aims: Insulin resistance and cytokine production are key mechanisms leading to fatty change in the liver and may produce nonalcoholic steatohepatitis (NASH). Oxidative stress may also contribute to clinical progression from simple fatty liver (FL) to NASH. A therapy for insulin resistance and antioxidant has been applied to treat NASH, yet these treatments are not fully established. In the present study, we have evaluated whether an antioxidant agent, glutathione, prevents the development of NASH from FL. Materials and methods: Five patients with FL and 10 with NASH were enrolled in the study. Three hundred milligrams per day of glutathione was given orally to patients with nonalcoholic fatty liver disease (NAFLD) every day, and an oxidative stress marker and biochemical tests were analyzed before treatment and 1 and 3 months after starting the treatment. We measured serum levels of 8-hydroxy- 2-deoxyguanosine (8-OHdG) and gamma-glutamyltranspeptidase (GGT). Immunohistochemistry for glutathione was performed on formalin fixed liver specimens obtained from liver biopsies. Results: Before treatment, the NASH group had higher serum 8-OHdG and lower serum glutathione levels than the FL group. Immunohistochemistry revealed that a strong expression of glutathione was observed in zone 3 in both NASH and FL before treatment. Serum levels of alanine transaminase and 8-OHdG were significantly decreased after treatment in the NASH group. Gamma-glutamyltranspeptidase was decreased after treatment, although the decrease was statistically not significant. Discussion: The present pilot study demonstrated that antioxidant therapy with glutathione may reduce the pathological oxidative stress in the liver in NASH, preventing the progression from NAFLD to NASH.

PDF Share
  1. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the Figs 4A and B: Immunohistochemical staining of glutathione in liver tissues. Immunoreactivity glutathione was strongly expressed in the cytoplasm of hepatocytes in an FL tissue; (A) as well as in a NASH tissue; (B) in the liver lobule zones 3 (× 200). There were no differences in the localization, but immunoreactivity of glutathione expression is stronger in an FL tissue than in an NASH tissue; and (C) Central vein A B Makoto Irie et al 18 American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012 Jun;55(6):2005-2023
  2. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 2010 Feb;51(2):679-689
  3. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 2013 May 10;5(5): 1544-1560
  4. The role of insulin-sensitizing agents in the treatment of nonalcoholic steatohepatitis. Therap Adv Gastroenterol 2011 Jul;4(4):249-263
  5. Nonalcoholic fatty liver disease. Best Pract Res Clin Gastroenterol 2010 Oct;24(5): 695-708
  6. Hydroxyl free radical mediated formation of 8-hydroxyguanine in isolated DNA. Arch Biochem Biophys 1988 Apr;262(1): 266-272
  7. Quantitative immunohistochemical determination of 8-hydroxy-2-deoxyguanosine by a monoclonal antibody N45.1: its application to ferric nitrilotriacetate-induced renal carcinogenesis model. Lab Invest 1997 Mar;76(3):365-374
  8. Role of oxidative DNA damage in cancer initiation and promotion. Eur J Cancer Prev 1998 Feb;7(1):9-16
  9. γ-Glutamyl transferase: a marker of nonalcoholic fatty liver disease in patients with the metabolic syndrome. Eur J Gastroenterol Hepatol 2012 Jul;24(7):805-810
  10. The association of serum gammaglutamyltransferase with components of the metabolic syndrome in the Korean adults. Diabetes Res Clin Pract 2007 Aug;77(2):306-313
  11. Levels of the oxidative stress marker γ-glutamyltranspeptidaseat different stages of nonalcoholic fatty liver disease. J Int Med Res 2012;40(3): 924-933
  12. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol 1997 Jul;27(1):103-107
  13. Nateglinide is useful for nonalcoholic steatohepatitis (NASH) patients with type 2 diabetes. Hepatogastroenterology 2005 Sep-Oct;52(65):1338-1343
  14. Hepatic expression of gamma-glutamyltranspeptidase in the human liver of patients with alcoholic liver disease. Hepatol Res 2007 Nov;37(11):966-973
  15. Insulin resistance accelerates a dietary rat model of nonalcoholic steatohepatitis. Gastroenterology 2007 Jan;132(1):282-293
  16. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic Biol Med 2012 Jan 1; 52(1):59-69
  17. The role of small intestinal bacterial overgrowth, intestinal permeability, endo-toxaemia, and tumour necrosis factor αin the pathogenesis of non-alcoholic steatohepatitis. Gut 2001 Feb;48(2):206-211
  18. Influence of TNF gene polymorphisms in Japanese patients with NASH and simple steatosis. J Hepatol 2007 Jun;46(6):1104-1110
  19. Oxidative stress and antioxidant defenses in serum of patients with non-alcoholic steatohepatitis. Clin Biochem 2007 Jul;40(11):776-780
  20. Non-alcoholic fatty liver disease. Crit Rev Clin Lab Sci 2011 May-Jun;48(3):97-113
  21. Blood oxidative stress markers in non-alcoholic steatohepatitis and how it correlates with diet. Scand J Gastroenterol 2008 Jan;43(1):95-102
  22. Effects of glutamine on oxidative stress and nuclear factor-κB expression in the livers of rats with nonalcoholic fatty liver disease. Exp Ther Med 2014 Feb;7(2):365-370
  23. Oral N-acetylcysteine rescues lethality of hepatocyte-specific Gclc-knockout mice, providing a model for hepatic cirrhosis. J Hepatol 2010 Dec;53(6):1085-1094.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.