title: Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice.
abstract: 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.
  
  
  CONCLUSIONS
  Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawai
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakatsuka
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Naofumi
authors.initials: N
authors.lastname: Tamaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koike
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Tsuzaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shiraha
authors.forename: Manabu
authors.initials: M
authors.lastname: Morita
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D018450:Disease Progression; D005234:Fatty Liver / Q000150:complications / Q000517:prevention & control*; D006859:Hydrogen / Q000032:analysis / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000150:complications / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014867:Water / Q000737:chemistry
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014867:Water; D006859:Hydrogen; D000077205:Pioglitazone