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Gen Thorac Cardiovasc Surg. 2019 Aug 29. doi: 10.1007/s11748-019-01195-3. [Epub ahead of print]

Hydrogen water alleviates obliterative airway disease in mice.

Author information

1
Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. naokiozeki@med.nagoya-u.ac.jp.
2
Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
3
Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
4
Specimen Preparation Room for Optical Microscopic Examinations, Core Clinical Research Hospital Support Room, Nagoya University Graduate School of Medicine, Nagoya, Japan.
5
Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
6
MiZ Company Limited, Kamakura, Japan.

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.

KEYWORDS:

Bronchiolitis obliterans syndrome; Forkhead box P3; Hydrogen; Lung transplantation; Regulatory T cell

PMID:
31468277
DOI:
10.1007/s11748-019-01195-3

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