Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration
Kentaro Noda
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
These authors contributed to this work equally.
Search for more papers by this authorYugo Tanaka
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
These authors contributed to this work equally.
Search for more papers by this authorNorihisa Shigemura
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorTomohiro Kawamura
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorYinna Wang
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorKosuke Masutani
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
Search for more papers by this authorXuejun Sun
Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
Search for more papers by this authorYoshiya Toyoda
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorChristian A. Bermudez
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorAtsunori Nakao
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
Department of Emergency and Critical Care Medicine, Hyogo College of Medicine, Hyogo, Japan
Search for more papers by this authorKentaro Noda
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
These authors contributed to this work equally.
Search for more papers by this authorYugo Tanaka
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
These authors contributed to this work equally.
Search for more papers by this authorNorihisa Shigemura
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorTomohiro Kawamura
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorYinna Wang
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorKosuke Masutani
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
Search for more papers by this authorXuejun Sun
Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, China
Search for more papers by this authorYoshiya Toyoda
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorChristian A. Bermudez
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Search for more papers by this authorAtsunori Nakao
Department of Cardiothoracic Surgery, Pittsburgh, PA, USA
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA
Department of Emergency and Critical Care Medicine, Hyogo College of Medicine, Hyogo, Japan
Search for more papers by this authorConflicts of Interest: All authors declare no conflict of interest exists.
Summary
Recent evidence suggests that molecular hydrogen has therapeutic value for disease states that involve inflammation. We hypothesized that drinking hydrogen-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 transplantation 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 → Mg (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 presence of hydrogen in vitro, accompanied by less production of interleukin-2 and interferon-γ. 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 hyperplasia of aortic allografts.
Supporting Information
Table S1. Experimental groups.
Table S2. Nucleotide sequences of oligonucleotide primers (RT-PCR).
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