J Korean Surg Soc.
2008 May;74(5):323-329.
Low Dose Carbon Monoxide Inhalation Prevents Chronic Allograft Nephropathy following Kidney Transplantation in Rats. Heme Oxygenase-1 Derivatives Study I
- Affiliations
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- 1Department of Surgery, Kosin University College of Medicine, Busan, Korea. ymh479@ns.kosinmed.or.kr
Abstract
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PURPOSE: Carbon monoxide (CO), a product of heme catalysis by heme oxygenase (HO-1, HO-2, HO-3), induces cytoprotection against ischemia/reperfusion (I/R) injury in a variety of organs such as the heart, lungs, kidneys, and liver. I examined whether CO would prevent chronic allograft nephropathy (CAN) associated with renal transplantation in rats.
METHODS
Kidneys from male Fisher rats were perfused and harvested for transplantation. Lewis rats were used as recipients. After reperfusion of the implanted kidney, the recipient's remaining kidney was removed promptly. Recipients were then immediately treated with the indicated regimen of CO in a Plexiglas exposure chamber. At 90 days after transplantation, the animals were sacrificed for graft histopathology, serum creatinine, and blood urea nitrogen (BUN) as markers of kidney function.
RESULTS
CAN in rats was achieved using a model of Fisher-to-Lewis transplants and evaluating kidney function over the 90 days following transplantation. CO administered at 100 ppm for 1 hr/day for 7 days prevented CAN at 90 days post-transplant. CO also decreased histopathological alterations, including leukocyte infiltration and cell death.
CONCLUSION
These data expand our understanding of the protective effects of low-dose CO inhalation in preventing the development of chronic fibro-inflammatory changes associated with chronic allograft nephropathy and allow us to devise methods for improving long-term renal allograft function.