Hydrogen Water Alleviates Obliterative Airway Disease in Mice

Gen Thorac Cardiovasc Surg. 2020 Feb;68(2):158-163. doi: 10.1007/s11748-019-01195-3. Epub 2019 Aug 29.

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.

MeSH terms

  • Airway Obstruction / etiology
  • Allografts
  • Animals
  • Bronchiolitis Obliterans / physiopathology
  • Bronchiolitis Obliterans / prevention & control*
  • Disease Models, Animal*
  • Enzyme-Linked Immunosorbent Assay
  • Hydrogen*
  • Immunosuppressive Agents
  • Lung / physiopathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Trachea / transplantation*
  • Transplantation, Homologous
  • Water / administration & dosage*

Substances

  • Immunosuppressive Agents
  • Water
  • Hydrogen