Ex vivo carbon monoxide prevents cytochrome P450 degradation and ischemia/reperfusion injury of kidney grafts

Atsunori Nakao, Gaetano Faleo, Hiroko Shimizu, Kiichi Nakahira, Junichi Kohmoto, Ryujiro Sugimoto, Augustine M.K. Choi, Kenneth R. McCurry, Toru Takahashi, Noriko Murase

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Renal ischemia/reperfusion injury is a major complication of kidney transplantation. We tested if ex vivo delivery of carbon monoxide (CO) to the kidney would ameliorate the renal injury of cold storage that can complicate renal transplantation. Orthotopic syngeneic kidney transplantation was performed in Lewis rats following 24 h of cold preservation in University of Wisconsin solution equilibrated without or with CO (soluble CO levels about 40 μM). Ischemia/reperfusion injury in control grafts resulted in an early upregulation of inflammatory mediator mRNAs and progressive deterioration of graft function. In contrast, the grafts preserved with CO had significantly less oxidative injury and this was associated with improved recipient survival compared to the control group. Renal injury in the control group showed considerable degradation of cytochrome P450 heme proteins, active heme metabolism and increased detrimental intracellular free heme levels. Kidney grafts preserved in CO-equilibrated solution maintained their cytochrome P450 protein levels, had normal intracellular heme levels and had less lipid peroxidation. Our results show that CO-mediated suppression of injurious heme-derived redox reactions offers protection of kidney grafts from cold ischemia/reperfusion injury.

Original languageEnglish (US)
Pages (from-to)1009-1016
Number of pages8
JournalKidney international
Issue number8
StatePublished - Oct 2008


  • Carbon monoxide
  • Cytochrome P450
  • Heme
  • Ischemia/reperfusion injury
  • Kidney transplantation

ASJC Scopus subject areas

  • Nephrology


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