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Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

Nature Medicine volume 13, pages 688694 (2007) | Download Citation

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Abstract

Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H2) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H2 selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H2 did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H2 gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H2 can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.

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Acknowledgements

This work was supported by grants to S.O. from the Ministry of Health, Labor and Welfare (H17-Chouju-009, longevity science; and 17A-10, nervous and mental disorders) and the Ministry of Education, Culture, Sports, Science and Technology (16390257).

Author information

Affiliations

  1. Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki City 211-8533, Japan.

    • Ikuroh Ohsawa
    • , Masahiro Ishikawa
    • , Kumiko Takahashi
    • , Megumi Watanabe
    • , Kiyomi Nishimaki
    • , Kumi Yamagata
    • , Sadamitsu Asoh
    •  & Shigeo Ohta
  2. Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.

    • Megumi Watanabe
    • , Ken-ichiro Katsura
    •  & Yasuo Katayama

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Contributions

S.O. conceived the experiments. S.O., I.O., K.K. and Y.K. designed the experiments. I.O., S.A. and S.O. performed data analysis. I.O., M.I., K.T., M.W., K.N, K.Y., S.A. and S.O. performed the experiments. S.O. and I.O. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Shigeo Ohta.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Molecular hydrogen dissolved in culture medium does not reduce cellular hydrogen peroxide and nitric oxide.

  2. 2.

    Supplementary Fig. 2

    pH, H2 and O2 maintain constant in culture medium in a closed flask filled with a mixed gas.

  3. 3.

    Supplementary Fig. 3

    Several methods confirm protection of cells by H2 against oxidative stress.

  4. 4.

    Supplementary Fig. 4

    Molecular hydrogen protects cultured neurons from ischemia and reperfusion in vitro.

  5. 5.

    Supplementary Fig. 5

    Cerebral blood flow is not influenced by H2 inhalation.

  6. 6.

    Supplementary Fig. 6

    The brain after induction of ischemia reperfusion injury with or without H2 treatment was immunostained.

  7. 7.

    Supplementary Table 1

    Physiological parameters during cerebral ischemia reperfusion

  8. 8.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nm1577

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