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Hydrogen water alleviates obliterative airway disease in mice

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Abstract

Objective

Bronchiolitis obliterans syndrome arising from chronic airway inflammation is a leading cause of death following lung transplantation. Several studies have suggested that inhaled hydrogen can protect lung grafts from ischemia–reperfusion injury via anti-inflammatory and -oxidative mechanisms. We investigated whether molecular hydrogen-saturated water can preserve lung allograft function in a heterotopic tracheal allograft mouse model of obliterative airway disease

Methods

Obliterative airway disease was induced by heterotopically transplanting tracheal allografts from BALB/c donor mice into C57BL/6 recipient mice, which were subsequently administered hydrogen water (10 ppm) or tap water (control group) (n = 6 each) daily without any immunosuppressive treatment. Histological and immunohistochemical analyses were performed on days 7, 14, and 21.

Results

Hydrogen water decreased airway occlusion on day 14. No significant histological differences were observed on days 7 or 21. The cluster of differentiation 4/cluster of differentiation 3 ratio in tracheal allografts on day 14 was higher in the hydrogen water group than in control mice. Enzyme-linked immunosorbent assay performed on day 7 revealed that hydrogen water reduced the level of the pro-inflammatory cytokine interleukin-6 and increased that of forkhead box P3 transcription factor, suggesting an enhancement of regulatory T cell activity.

Conclusions

Hydrogen water suppressed the development of mid-term obliterative airway disease in a mouse tracheal allograft model via anti-oxidant and -inflammatory mechanisms and through the activation of Tregs. Thus, hydrogen water is a potential treatment strategy for BOS that can improve the outcome of lung transplant patients.

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Acknowledgement

We thank Dr. Koji Kawaguchi, Dr. Takayuki Fukui, Dr. Shota Nakamura, Dr. Shunsuke Mori, and Dr. Kohei Yokoi for all their help and guidance.

Funding

This work was supported by MiZ Co., Ltd. (Kamakura, Japan). S. Hirano and R. Kurokawa are board members of MiZ Co., Ltd.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Naoki Ozeki

  2. Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Aika Yamawaki-Ogata, Yuji Narita & Akihiko Usui

  3. Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Shinji Mii & Kaori Ushida

  4. Specimen Preparation Room for Optical Microscopic Examinations, Core Clinical Research Hospital Support Room, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kaori Ushida

  5. Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Mikako Ito & Kinji Ohno

  6. MiZ Company Limited, Kamakura, Japan

    Shin-ichi Hirano & Ryosuke Kurokawa

Authors
  1. Naoki Ozeki
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  2. Aika Yamawaki-Ogata
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Correspondence to Naoki Ozeki.

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Ozeki, N., Yamawaki-Ogata, A., Narita, Y. et al. Hydrogen water alleviates obliterative airway disease in mice. Gen Thorac Cardiovasc Surg 68, 158–163 (2020). https://doi.org/10.1007/s11748-019-01195-3

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  • DOI: https://doi.org/10.1007/s11748-019-01195-3

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