Carbon monoxide inhalation ameliorates cold ischemia/reperfusion injury after rat liver transplantation.
BACKGROUND
Carbon monoxide (CO), a product of heme degradation by heme oxygenase, induces cytoprotection against ischemia/reperfusion (I/R) injury in a variety of organs such as the heart, lung, kidney, and small intestine. We examined whether CO would protect liver grafts against cold I/R injury associated with transplantation.


METHODS
Orthotopic liver transplantation (OLT) was performed in syngeneic Lewis rats with 18 hours preservation in cold University of Wisconsin solution. Recipients were exposed to air or CO (100 ppm) for 1 hour before and 24 hours after OLT. Recipients were sacrificed 0.5 to 48 hours post-transplant.


RESULTS
CO inhalation significantly decreased serum aspartate aminotransferase and alanine aminotransferase levels and suppressed hepatic necrosis formation and neutrophil accumulation at 6 to 48 hours after OLT, compared with air control. The expressions of tumor necrosis factor alpha, intercellular adhesion molecule 1, and inducible nitric oxide synthase messenger RNA in the liver graft were significantly inhibited in the CO-treated group at 1 hour after reperfusion. Hepatic nuclear factor-kappaB activation did not differ between the groups.


CONCLUSIONS
The results demonstrate that exogenous CO treatment suppresses early proinflammatory gene expression and neutrophil infiltration, and efficiently ameliorates hepatic I/R injury. The possible mechanism by which CO protects the liver against cold I/R does not seem to be associated with downregulation of the nuclear factor-kappaB-signaling pathway.
Kaizu
Takashi
T
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, PA 15213, USA.
Nakao
Atsunori
A
Tsung
Allan
A
Toyokawa
Hideyoshi
H
Sahai
Rohit
R
Geller
David A
DA
Murase
Noriko
N
D000280:Administration, Inhalation; D000818:Animals; D002248:Carbon Monoxide / Q000097:blood / Q000494:pharmacology*; D015925:Cryopreservation; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006454:Hemoglobins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016031:Liver Transplantation; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D006454:Hemoglobins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat