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

Abstract

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 4 h 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.

Study details

Article type

Original Research

Disease / injury model

Ischemia/reperfusion injury in lung transplantation (rat model)

Duration

7 hours

Dose-dependent effect

No

Outcome

Positive

Findings

Hydrogen ventilation of donor rat lungs prior to procurement upregulated surfactant-related genes, ATP synthase genes, and stress-response genes, increased tissue ATP and HSP70, and induced C/EBPα/β, suggesting a molecular basis for hydrogen's protective effects against ischemia/reperfusion injury in lung transplantation.