Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan.
Hepatology. 2012 Sep;56(3):912-21. doi: 10.1002/hep.25782. Epub 2012 Jul 17.
Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen is an effective antioxidant that reduces cytotoxic reactive oxygen species. In this study, we investigated the effects of hydrogen-rich water and the drug pioglitazone on the progression of NASH in mouse models. A methionine-choline-deficient (MCD) diet mouse model was prepared. Mice were divided into three experimental groups and fed for 8 weeks as follows: (1) MCD diet + control water (CW group); (2) MCD diet + hydrogen-rich water (HW group); and (3) MCD diet mixed with pioglitazone (PGZ group). Plasma alanine aminotransferase levels, hepatic expression of tumor necrosis factor-α, interleukin-6, fatty acid synthesis-related genes, oxidative stress biomarker 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis marker terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells in the liver were decreased in the HW and PGZ groups. The HW group showed a smaller decrease in hepatic cholesterol; however, stronger antioxidative effects in serum and lower peroxisome proliferator-activated receptor-α expression in the liver were seen in comparison with the PGZ group. We then investigated the effects of hydrogen in the prevention of hepatocarcinogenesis in STAM mice, known as the NASH-related hepatocarcinogenesis model. Eight-week-old male STAM mice were divided into three experimental groups as follows: (1) control water (CW-STAM); (2) hydrogen-rich water (HW-STAM); and (3) pioglitazone (PGZ-STAM). After 8 weeks, hepatic tumors were evaluated. The number of tumors was significantly lower in the HW-STAM and PGZ-STAM groups than in the CW-STAM group. The maximum tumor size was smaller in the HW-STAM group than in the other groups.
Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis.
氧化应激是从单纯性脂肪肝发展为非酒精性脂肪性肝炎（NASH）的主要原因。分子氢是一种有效的抗氧化剂，可减少细胞毒性活性氧。本研究旨在探讨富氢水和药物吡格列酮对 NASH 进展的影响。制备了蛋氨酸-胆碱缺乏（MCD）饮食小鼠模型。将小鼠分为三组进行实验，喂养 8 周：（1）MCD 饮食+对照水（CW 组）；（2）MCD 饮食+富氢水（HW 组）；和（3）MCD 饮食混合吡格列酮（PGZ 组）。HW 组和 PGZ 组的血浆丙氨酸氨基转移酶水平、肝脏肿瘤坏死因子-α、白细胞介素-6、脂肪酸合成相关基因、氧化应激生物标志物 8-羟基脱氧鸟苷（8-OHdG）和肝内凋亡标志物末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）阳性细胞减少。HW 组肝脏胆固醇减少较少，但与 PGZ 组相比，血清中抗氧化作用更强，肝脏过氧化物酶体增殖物激活受体-α表达水平更低。然后，我们研究了氢气在预防 STAM 小鼠（即 NASH 相关肝癌发生模型）肝癌发生中的作用。将 8 周龄雄性 STAM 小鼠分为三组：（1）对照水（CW-STAM）；（2）富氢水（HW-STAM）；和（3）吡格列酮（PGZ-STAM）。8 周后评估肝肿瘤。HW-STAM 和 PGZ-STAM 组的肿瘤数量明显少于 CW-STAM 组。HW-STAM 组的最大肿瘤尺寸小于其他组。
富氢水的摄入可能通过减少肝脏氧化应激、细胞凋亡、炎症和肝癌发生来有效治疗 NASH。
