| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Thomas E. Starzl Transplantation Institute, 3Center for Biologic Imaging, Departments of 2Surgery, 6Pulmonary Allergy and Critical Care Medicine, 4Anesthesiology and Critical Care Medicine, and 5Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261
Submitted 30 April 2004 ; accepted in final form 26 July 2004
Carbon monoxide (CO), a product of heme metabolism by heme oxygenases, is known to impart protection against oxidative stress. We hypothesized that CO would protect ischemia-reperfusion (I/R) injury of transplanted organs, and the efficacy of CO was studied in the rat kidney transplantation model. A Lewis rat kidney graft, preserved in University of Wisconsin solution at 4°C for 24 h, was orthotopically transplanted into syngeneic rats. Recipients were maintained in room air or exposed to CO (250 ppm) in air for 1 h before and 24 h after transplantation. Animals were killed 1, 3, 6, and 24 h after transplantation to assess efficacy of inhaled CO. Rapid upregulation of mRNA for IL-6, IL-1
, TNF-
, ICAM-1, heme oxygenase-1, and inducible nitric oxide synthase was observed within 3 h after transplantation in the control grafts of air-exposed recipients, associating with histopathological evidences of acute tubular necrosis, interstitial hemorrhage, and edema. In contrast, the increase of inflammatory mediators was markedly inhibited in kidney grafts of CO-treated recipients, which correlated with improved renal cortical blood flow. Further detailed morphological analyses revealed that CO preserved the glomerular vascular architecture and podocyte viability with less apoptosis of tubular epithelial cells and less ED1+ macrophage infiltration. CO inhalation resulted in improved serum creatinine levels and clearance, and animal survival was significantly improved with CO to 60.5 from 25 days in untreated controls. The study demonstrates that exposure of kidney graft recipients to CO at a low concentration can impart significant protective effects against renal I/R injury and improve function of renal grafts.
kidney transplantation; heme oxygenase; oxidative stress; cold preservation
This article has been cited by other articles:
|
|
 |
|
  N. G. Abraham, J. Cao, D. Sacerdoti, X. Li, and G. Drummond Heme oxygenase: the key to renal function regulation Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1137 - F1152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Nakao, G. Faleo, M. A. Nalesnik, J. Seda-Neto, J. Kohmoto, and N. Murase Low-dose carbon monoxide inhibits progressive chronic allograft nephropathy and restores renal allograft function Am J Physiol Renal Physiol, July 1, 2009; 297(1): F19 - F26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, J.-Y. S. Lee, J. H. Kwak, Y. He, S. I. Kim, and M. E. Choi Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction Am J Physiol Renal Physiol, March 1, 2008; 294(3): F508 - F517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Stec, H. A. Drummond, and T. Vera Role of Carbon Monoxide in Blood Pressure Regulation Hypertension, March 1, 2008; 51(3): 597 - 604. [Full Text] [PDF]
|
|
|
|
 |
|
 M. P Mattson Hormesis and disease resistance: activation of cellular stress response pathways Human and Experimental Toxicology, February 1, 2008; 27(2): 155 - 162. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Kaizu, A. Ikeda, A. Nakao, A. Tsung, H. Toyokawa, S. Ueki, D. A. Geller, and N. Murase Protection of transplant-induced hepatic ischemia/reperfusion injury with carbon monoxide via MEK/ERK1/2 pathway downregulation Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G236 - G244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hochegger, T. Schatz, P. Eller, A. Tagwerker, D. Heininger, G. Mayer, and A. R. Rosenkranz Role of {alpha}/beta and {gamma}/{delta} T cells in renal ischemia-reperfusion injury Am J Physiol Renal Physiol, September 1, 2007; 293(3): F741 - F747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kirkby, C. Baylis, A. Agarwal, B. Croker, L. Archer, and C. Adin Intravenous bilirubin provides incomplete protection against renal ischemia-reperfusion injury in vivo Am J Physiol Renal Physiol, February 1, 2007; 292(2): F888 - F894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Devarajan Update on Mechanisms of Ischemic Acute Kidney Injury J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1503 - 1520. [Full Text] [PDF]
|
|
|
|
|
|
K. A. Kirkby and C. A. Adin Products of heme oxygenase and their potential therapeutic applications Am J Physiol Renal Physiol, March 1, 2006; 290(3): F563 - F571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Neto, A. Nakao, H. Toyokawa, M. A. Nalesnik, A. J. Romanosky, K. Kimizuka, T. Kaizu, N. Hashimoto, O. Azhipa, D. B. Stolz, et al. Low-dose carbon monoxide inhalation prevents development of chronic allograft nephropathy Am J Physiol Renal Physiol, February 1, 2006; 290(2): F324 - F334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Morse and A. M. K. Choi Heme Oxygenase-1: From Bench to Bedside Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 660 - 670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vera, J. R. Henegar, H. A. Drummond, J. M. Rimoldi, and D. E. Stec Protective Effect of Carbon Monoxide-Releasing Compounds in Ischemia-Induced Acute Renal Failure J. Am. Soc. Nephrol., April 1, 2005; 16(4): 950 - 958. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
