Irie Makoto, Sohda Tetsuro, Anan Akira, Fukunaga Atsushi, Takata Kazuhide, Tanaka Takashi, Yokoyama Keiji, Morihara Daisuke, Takeyama Yasuaki, Shakado Satoshi, Sakisaka Shotaro
Department of Gastroenterology and Medicine, Fukuoka University, Faculty of Medicine, Fukuoka, Japan.
Euroasian J Hepatogastroenterol. 2016 Jan-Jun;6(1):13-18. doi: 10.5005/jp-journals-10018-1159. Epub 2016 Jul 9.
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.
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.
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.
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.
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.
胰岛素抵抗和细胞因子生成是导致肝脏脂肪变性的关键机制,可能引发非酒精性脂肪性肝炎(NASH)。氧化应激也可能促使单纯性脂肪肝(FL)向NASH临床进展。一种针对胰岛素抵抗和抗氧化的治疗方法已应用于NASH的治疗,但这些治疗方法尚未完全确立。在本研究中,我们评估了抗氧化剂谷胱甘肽是否能预防FL发展为NASH。
纳入5例FL患者和10例NASH患者。每天给非酒精性脂肪性肝病(NAFLD)患者口服300毫克谷胱甘肽,并在治疗前以及开始治疗后1个月和3个月分析氧化应激标志物和生化指标。我们检测了血清8-羟基-2-脱氧鸟苷(8-OHdG)和γ-谷氨酰转肽酶(GGT)水平。对从肝活检获取的福尔马林固定肝脏标本进行谷胱甘肽免疫组化检测。
治疗前,NASH组血清8-OHdG水平高于FL组,血清谷胱甘肽水平低于FL组。免疫组化显示,治疗前NASH组和FL组的3区均观察到谷胱甘肽的强表达。NASH组治疗后血清丙氨酸转氨酶和8-OHdG水平显著降低。治疗后γ-谷氨酰转肽酶降低,尽管降低幅度无统计学意义。
本初步研究表明,谷胱甘肽抗氧化治疗可能减轻NASH患者肝脏的病理性氧化应激,防止NAFLD进展为NASH。
Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, Yokoyama K, Morihara D, Takeyama Y, Shakado S, Sakisaka S. 还原型谷胱甘肽抑制非酒精性脂肪性肝病中的氧化应激。《欧亚肝脏胃肠病学杂志》2016;6(1):13 - 18。