title: Oral intake of hydrogen-rich water inhibits intimal hyperplasia in arterialized vein grafts in rats.
abstract: OBJECTIVE
  Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia.
  
  
  RESULTS
  The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H(2)O → Mg (OH)(2) + H(2)). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration.
  
  
  CONCLUSIONS
  Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life.
authors.affiliation: Department of Cardiothoracic Surgery,  University of Pittsburgh Medical Center, Pittsburgh, PA,  USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawamura
authors.forename: Kosuke
authors.initials: K
authors.lastname: Masutani
authors.forename: Ximei
authors.initials: X
authors.lastname: Peng
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.forename: John P
authors.initials: JP
authors.lastname: Pribis
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.forename: Christian A
authors.initials: CA
authors.lastname: Bermudez
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D001012:Aorta, Abdominal / Q000601:surgery; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000097:blood; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004326:Drinking; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D006801:Humans; D006859:Hydrogen / Q000008:administration & dosage* / Q000097:blood; D006965:Hyperplasia; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014185:Transplantation, Isogeneic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058017:Vascular Grafting / Q000009:adverse effects*; D014682:Vena Cava, Inferior / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002317:Cardiovascular Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D006859:Hydrogen; D048051:p38 Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat