Hydrogen inhalation ameliorates oxidative stress in transplantation induced intestinal graft injury

B. M. Buchholz, D. J. Kaczorowski, R. Sugimoto, R. Yang, Y. Wang, T. R. Billiar, K. R. McCurry, A. J. Bauer, A. Nakao

Research output: Contribution to journalArticlepeer-review

272 Citations (Scopus)


Ischemia/reperfusion (I/R) injury during small intestinal transplantation (SITx) frequently causes complications including dysmotility, inflammation and organ failure. Recent evidence indicates hydrogen inhalation eliminates toxic hydroxyl radicals. Syngeneic, orthotopic SITx was performed in Lewis rats with 3 h of cold ischemic time. Both donor and recipient received perioperative air or 2% hydrogen inhalation. SITx caused a delay in gastrointestinal transit and decreased jejunal circular muscle contractile activity 24 h after surgery. Hydrogen treatment resulted in significantly improved gastrointestinal transit, as well as jejunal smooth muscle contractility in response to bethanechol. The transplant induced upregulation in the inflammatory mediators CCL2, IL-1β, IL-6 and TNF-α were mitigated by hydrogen. Hydrogen significantly diminished lipid peroxidation compared to elevated tissue malondialdehyde levels in air-treated grafts demonstrating an antioxidant effect. Histopathological mucosal erosion and increased gut permeability indicated a breakdown in posttransplant mucosal barrier function which was significantly attenuated by hydrogen treatment. In recipient lung, hydrogen treatment also resulted in a significant abatement in inflammatory mRNA induction and reduced neutrophil recruitment. Hydrogen inhalation significantly ameliorates intestinal transplant injury and prevents remote organ inflammation via its antioxidant effects. Administration of perioperative hydrogen gas may be a potent and clinically applicable therapeutic strategy for intestinal I/R injury.

Original languageEnglish
Pages (from-to)2015-2024
Number of pages10
JournalAmerican Journal of Transplantation
Issue number10
Publication statusPublished - Oct 2008
Externally publishedYes


  • Gastrointestinal motility
  • Hydrogen
  • Inflammation
  • Intestinal transplantation
  • Oxidative stress

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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