Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant.
BACKGROUND
Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT.


METHODS
We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed.


RESULTS
Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue.


CONCLUSIONS
The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.
Liver Research Unit, Instituto Maimónides para la Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain. p.aguilar.melero@gmail.com
Patricia
P
Aguilar-Melero
Antonio
A
Luque
María M
MM
Machuca
María P
MP
Pérez de Obanos
Rocío
R
Navarrete
Inés C
IC
Rodríguez-García
Javier
J
Briceño
María
M
Iñiguez
Juan
J
Ruiz
Jesús
J
Prieto
Manuel
M
de la Mata
Rafael J
RJ
Gomez-Villamandos
Jordi
J
Muntane
Pedro
P
López-Cillero
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006439:Hemodynamics / Q000187:drug effects; D006498:Hepatectomy; D018836:Inflammation Mediators / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D016031:Liver Transplantation / Q000401:mortality; D018384:Oxidative Stress / Q000187:drug effects; D011300:Preoperative Care / Q000379:methods*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D013552:Swine; D020858:Tissue and Organ Harvesting
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D020011:Protective Agents; C092073:cardiotrophin 1