July 2016
Makoto Irie, Tetsuro Sohda, Akira Anan, Atsushi Fukunaga, Kazuhide Takata, Takashi Tanaka, Keiji Yokoyama, Daisuke Morihara, Yasuaki Takeyama, Satoshi Shakado, and Shotaro Sakisaka

 

ABSTRACT

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.

 

How to cite this article

Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S. Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(1):13-18.

Keywords: 8-Hydroxy-2-deoxyguanosine, Gamma-glutamyltranspeptidase, Glutathione, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis.