Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement

Biochem Biophys Res Commun. 2012 Sep 7;425(4):873-9. doi: 10.1016/j.bbrc.2012.08.005. Epub 2012 Aug 7.


Background: We previously demonstrated that donor treatment with inhaled hydrogen protects lung grafts from cold ischemia/reperfusion (I/R) injury during lung transplantation. To elucidate the mechanisms underlying hydrogen's protective effects, we conducted a gene array analysis to identify changes in gene expression associated with hydrogen treatment.

Methods: Donor rats were exposed to mechanical ventilation with 98% oxygen and 2% nitrogen or 2% hydrogen for 3 h before harvest; lung grafts were stored for 4h in cold Perfadex. Affymetrix gene array analysis of mRNA transcripts was performed on the lung tissue prior to implantation.

Results: Pretreatment of donor lungs with hydrogen altered the expression of 229 genes represented on the array (182 upregulated; 47 downregulated). Hydrogen treatment induced several lung surfactant-related genes, ATP synthase genes and stress-response genes. The intracellular surfactant pool, tissue adenosine triphosphate (ATP) levels and heat shock protein 70 (HSP70) expression increased in the hydrogen-treated grafts. Hydrogen treatment also induced the transcription factors C/EBPα and C/EBPβ, which are known regulators of surfactant-related genes.

Conclusion: Donor ventilation with hydrogen significantly increases expression of surfactant-related molecules, ATP synthases and stress-response molecules in lung grafts. The induction of these molecules may underlie hydrogen's protective effects against I/R injury during transplantation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Hydrogen / administration & dosage*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung Transplantation*
  • Male
  • Pulmonary Surfactant-Associated Proteins / genetics*
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Reperfusion Injury / prevention & control*
  • Respiration, Artificial
  • Stress, Physiological / genetics
  • Tissue and Organ Harvesting / methods*
  • Tissue and Organ Procurement
  • Transcriptome*


  • CCAAT-Enhancer-Binding Proteins
  • Pulmonary Surfactant-Associated Proteins
  • Hydrogen