title: Carbon monoxide-releasing molecules protect against ischemia-reperfusion injury during kidney transplantation.
abstract: Carbon monoxide (CO) can provide beneficial antiapoptotic and anti-inflammatory effects in the context of ischemia-reperfusion injury (IRI). Here we tested the ability of pretreating the kidney donor with carbon monoxide-releasing molecules (CORM) to prevent IRI in a transplant model. Isogeneic Brown Norway donor rats were pretreated with CORM-2 18 h before kidney retrieval. The kidneys were then cold-preserved for 26 h and transplanted into Lewis rat recipients that had undergone bilateral nephrectomy. Allografts from Brown Norway to Lewis rats were also performed after 6 h of cold ischemic time with low-dose tacrolimus treatment. All recipients receiving CORM-2-treated isografts survived the transplant process and had near-normal serum creatinine levels, whereas all control animals died of uremia by the third post-operative day. This beneficial effect was also seen in isografted Lewis recipients receiving kidneys perfused with CORM-3, indicating that CORMs have direct effects on the kidney. Pretreatment of human umbilical vein endothelial cells in culture with CORM-2 for 1 h significantly reduced cytokine-induced nicotinamide adenine dinucleotide phosphate-dependent production of superoxide, activation of the inflammation-relevant transcription factor nuclear factor-κB, upregulated expression of E-selectin and intercellular adhesion molecule-1 adhesion proteins, and leukocyte adhesion to the endothelial cells. Thus, CORM-2-derived CO protects renal transplants from IRI by modulating inflammation.
authors.affiliation: Department of Surgery, University of Western Ontario, London, Ontario, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Caumartin
authors.forename: Jancy
authors.initials: J
authors.lastname: Stephen
authors.forename: Jian P
authors.initials: JP
authors.lastname: Deng
authors.forename: Dameng
authors.initials: D
authors.lastname: Lian
authors.forename: Zhu
authors.initials: Z
authors.lastname: Lan
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.forename: Bertha
authors.initials: B
authors.lastname: Garcia
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Jevnikar
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Gediminas
authors.initials: G
authors.lastname: Cepinskas
authors.forename: Patrick P W
authors.initials: PP
authors.lastname: Luke
mesh_terms: D000818:Animals; D007371:Interferon-gamma / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation / Q000401:mortality; D009249:NADP / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology; D009942:Organometallic Compounds / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D009942:Organometallic Compounds; D014409:Tumor Necrosis Factor-alpha; C447082:tricarbonyldichlororuthenium (II) dimer; D013481:Superoxides; D009249:NADP; D007371:Interferon-gamma