Reduced Glutathione suppresses Oxidative Stress in Nonalcoholic Fatty Liver Disease

Abstract

Background and aimsInsulin 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 methodsFive 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.ResultsBefore 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.DiscussionThe 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 articleIrie 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.

Burden of Alcoholic Liver Disease in a Tertiary Care Center: A Descriptive Cross-sectional Study

“…1,18,20 Increase in serum levels of ALP along with GGT suggests a liver pathology. 19 The De-ritis ratio was higher in patients with ALD (2.49±0.8) than that of NAFLD (0.87±0.27). Serum AST level was significantly higher than ALT in ALD groups which gave rise to higher De-ritis ratio, and this was similar to the studies done by Ram, et al 21 Junking, et al 1 Serum ALT is usually higher than AST in most causes of liver damage, but AST remains significantly higher in case of ALD.…”

“…18 Elevated GGT level was related to biological effect of alcohol consumption rather than amount of alcohol consumed, which induces the protein expression and increased synthesis of GGT. 19 Alcohol abuse causes damage to the liver cell causing release of GGT from microsomes into blood. Studies have shown that GGT has higher predictive value of ALD.…”

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

“…Of major concern, while the human body is designed to fend off such undesirable metabolic effects, the intracellular response systems such as antioxidants are also suppressed in conditions of NAFLD [ 81 , 82 ]. Importantly, a reduction in one of the major antioxidants within the human body such as GSH has been consistent with the progression from NAFLD to NASH in some patients [ 83 ]. Hence, GSH is an increasing target of pharmacological compounds that have the capacity to enhance intracellular antioxidant defence systems [ 19 , 20 , 21 , 22 ].…”

“…In addition, NAC shows an enhanced effect to improve liver function by reducing the levels of oxidative stress and pro-inflammatory markers such as IL-6, TNF-α and IL-1β, NF-κB, TGFβ-1, and MDA levels ( Table 2 , Figure 3 ). This appears to be mainly modulated through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, mainly GSH content [ 41 , 56 , 79 , 80 , 81 , 82 , 83 ]. Although there are very few clinical studies published on the topic, the evidence summarized in Table 4 suggests that daily intake of NAC at doses between 0.6–1 g is able to improve liver enzymes such as ALT and AST in patients with NAFLD.…”

Successful treatment of obesity and insulin resistance via ketogenic diet status post Roux-en-Y

“…Additionally, IR and cytokine production are key mechanisms leading to NASH 26. Acyl and acetyl CoA are both precursors to cholesterol synthesis 27.…”