Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice

Authors

  • Daisuke Kawai,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Akinobu Takaki,

    Corresponding author
    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
    • 2-5-1 Shikata Cho, Kita-Ku, Okayama City, Okayama 700-8558, Japan===

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    • fax: (81)-86-225-5991

  • Atsuko Nakatsuka,

    1. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Jun Wada,

    1. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Naofumi Tamaki,

    1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Tetsuya Yasunaka,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Kazuko Koike,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Ryuichiro Tsuzaki,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Kazuyuki Matsumoto,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Yasuhiro Miyake,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Hidenori Shiraha,

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Manabu Morita,

    1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Hirofumi Makino,

    1. Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Kazuhide Yamamoto

    1. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City, Okayama, Japan
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  • Potential conflict of interest: Nothing to report.

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. Conclusion: Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis. (HEPATOLOGY 2012;56:912–921)

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