Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration
Kentaro Noda, Yugo Tanaka, Norihisa Shigemura, Tomohiro Kawamura, Yinna Wang, Kosuke Masutani, Xuejun Sun, Yoshiya Toyoda, Christian A. Bermudez, Atsunori Nakao
Transplant International · 2012 · 25 · 1213–1222
Abstract
Recent evidence suggests that molecular hydrogen has therapeutic value for dis- ease states that involve inflammation. We hypothesized that drinking hydro- gen-rich water (HW) daily would protect cardiac and aortic allograft recipients from inflammation-associated deterioration. Heterotopic heart transplantation with short-course tacrolimus immunosuppression and orthotopic aortic trans- plantation were performed in allogeneic rat strains. HW was generated either by bubbling hydrogen gas through tap water (Bu-HW) or via chemical reaction using a magnesium stick [Mg + 2H2O fiMg (OH)2 + H2] immersed in tap water (Mg-HW). Recipients were given either regular water (RW), Mg-HW, Bu-HW, or Mg-HW that had been subsequently degassed (DW). Graft survival was assessed by daily palpation for a heartbeat. Drinking Mg-HW or Bu-HW was remarkably effective in prolonging heart graft survival and reducing intimal hyperplasia in transplanted aortas as compared with grafts treated with RW or DW. Furthermore, T cell proliferation was significantly inhibited in the pres- ence of hydrogen in vitro, accompanied by less production of interleukin-2 and interferon-c. Hydrogen treatment was also associated with increased graft ATP levels and increased activity of the enzymes in mitochondrial respiratory chain. Drinking HW prolongs survival of cardiac allografts and reduces intimal hyper- plasia of aortic allografts.
Study details
- Article type
- Original Research
- Disease / injury model
- Cardiac and aortic allograft transplantation (chronic rejection, vasculopathy)
- Duration
- 100 days
- Dose comparison
- Compared two concentrations of hydrogen in water (0.6 mM for Mg-HW, 0.5 mM for Bu-HW) and their effects on blood hydrogen levels and outcomes.
- Dose-dependent effect
- No
- Outcome
- Positive
- Findings
- Drinking hydrogen-rich water (HW) significantly prolonged cardiac allograft survival and reduced intimal hyperplasia in transplanted aortas in rats. HW also reduced inflammatory cell infiltration, oxidative injury, and pro-inflammatory cytokine/chemokine expression, while increasing ATP and mitochondrial enzyme activity in grafts. In vitro, hydrogen inhibited T cell proliferation and Th1 cytokine production. No adverse effects were observed.
Classification
- Research Topics
- Study Type
- Species
- Organs & Tissues
- Physiological Systems
- Biomarkers
- Adenosine triphosphate (ATP)CCL2 mRNACCL5 mRNACD3+ T cellsCD68+ macrophagesCitrate synthase activityIFN-γ mRNAInterferon Gamma (IFN-γ)Interleukin-10 (IL-10)Interleukin-2 (IL-2)Malondialdehyde (MDA)Mitochondrial Complex I activityMitochondrial Complex II/III activityMitochondrial Complex IV activityMitochondrial Complex V activityMyeloperoxidase (MPO) activityTumor Necrosis Factor Alpha (TNF-α)
- Methods of Administration
- Countries
- Also
- Highlighted ArticlesMethods of Administration ComparedDose/Concentration ComparedDrug/Therapy/Supplement ComparedPharmacokinetics DiscussedH2 Safety Discussed
