title: High-pressure carbon monoxide preserves rat kidney grafts from apoptosis and inflammation.
abstract: Renal ischemia-reperfusion (I/R) injury is unavoidable in kidney transplantation (KTx) and frequently influences both short- and long-term allograft survival. Carbon monoxide (CO) has attracted attention as a medical gas with anti-inflammatory and anti-apoptotic effects. We investigated a new strategy for organ preservation using ex vivo application of high-pressure CO in an experimental rat KTx model. We preserved kidney grafts using a high-pressure chamber filled with mixed gases composed of CO and O2. We found that cold I/R injury resulted in progressive deterioration of renal graft function in University of Wisconsin solution, whereas CO significantly improved renal function. We confirmed that CO decreased oxidative stress and mRNA expression of proinflammatory cytokines and inhibited tubular apoptosis in the early phases. Western blot analysis demonstrated that CO increased phosphatidylinositol-3 kinase and phosphorylation of Akt and p38 mitogen-activated protein kinase. Furthermore, CO significantly alleviated tubular injury scores and suppressed the development of interstitial fibrosis at 100 days after KTx. Thus, high-pressure mixed CO and O2gases successfully preserved rat kidney grafts for 24 h by protecting tubular epithelial cells from apoptosis and inhibiting inflammation.
authors.affiliation: Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Urology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yazawa
authors.affiliation: Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.|AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.affiliation: Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Imamura
authors.affiliation: Department of Anatomy, Tokyo Medical University, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hatayama
authors.affiliation: Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.affiliation: Department of Urology, Osaka General Medical Center, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsutahara
authors.affiliation: Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Masayoshi
authors.identifier: 0000-0001-7443-2621
authors.initials: M
authors.lastname: Okumi
authors.affiliation: Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Ichimaru
authors.affiliation: Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Jun-Ya
authors.initials: JY
authors.lastname: Kaimori
authors.affiliation: Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.affiliation: High Altitude Pathology Institute, La Paz, Bolivia.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Seki
authors.affiliation: Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.affiliation: Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
authors.affiliation: Department of Specific Organ Regulation (Urology), Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000494:pharmacology*; D003080:Cold Temperature; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D016030:Kidney Transplantation / Q000379:methods*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010313:Partial Pressure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011887:Raffinose / Q000494:pharmacology; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D002248:Carbon Monoxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D010100:Oxygen