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Adding a Hydrogen-producing Magnesium stick to the drinking water protects cardiac allografts and reduces allograft vasculopathy in rats
Atsunori Nakao, Sungsoo Lee, Chien-sheng Huang, Zhiliang Wang,
Norihisa Shigemura, Yoshiya Toyoda
Oxidative stress likely contributes to allograft vasculopathy and interstitial fibrosis, limiting long-term survival after cardiac transplantation. Molecular hydrogen (H2) has therapeutic value as an antioxidant through its ability to selectively reduce cytotoxic reactive oxygen species. We hypothesized that drinking hydrogen water (HW) would protect cardiac and aortic allograft recipients from allograft vasculopathy via the antioxidant and anti-inflammatory effects of H2. We further tested whether therapeutic HW could be generated via a magnesium (Mg) stick placed in the drinking water.
Allogeneic heterotopic heart transplantation (HTx) and aortic transplantation were performed in rats (LEW and BN) with tacrolimus immunosuppression (0.5 mg/kg, days 0-6). HW was generated either by bubbling hydrogen gas through tap water or with a Mg stick immersed in tap water (Mg + 2H2O → Mg (OH)2 + H2). For 100 continuous days, beginning the day of transplantation, recipients were given either regular water (RW), HW, or HW that had been subsequently degassed. Graft survival was assessed by daily palpation for a heartbeat. Aortic grafts were harvested at day 60 for histologic analysis.
Oral administration of HW generated with a Mg stick (H2 concentration: 0.6 mM) caused a significant elevation in blood H2 (up to 28.6 ± 2.9 µM 15 min after intake) as compared to RW (8.1 ± 0.4 µM). Supplementation of H2 in the drinking water, either by reaction with the Mg stick or by bubbling with H2 gas (0.5 mM), was remarkably effective in prolonging heart graft survival (median of >100 days for both) without adverse effects. In contrast, heart grafts survived 49.5 days in animals given RW and 51.5 days in animals given degassed HW. At day 50, there was a marked increase in graft infiltrating cells, including macrophages and T cells. HW reduced inflammatory cell infiltration and graft lipid peroxidation. Drinking HW also reduced intragraft mRNA levels for IFNγ at day 50. While Verhoeff’s van Gieson staining of transplanted aortas showed massive neointimal hyperplasia associated with the accumulation of αSMA-positive smooth muscle cells, HW treatment significantly reduced these pathological changes in aortic allografts.
Dissolving H2 in drinking water prolongs survival of cardiac allografts. Drinking HW may protect cardiac allografts from allograft vasculopathy. The HW-producing Mg stick may have novel therapeutic value in HTx due to its portability.