Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant. 2013

Patricia Aguilar-Melero, and Antonio Luque, and María M Machuca, and María P Pérez de Obanos, and Rocío Navarrete, and Inés C Rodríguez-García, and Javier Briceño, and María Iñiguez, and Juan Ruiz, and Jesús Prieto, and Manuel de la Mata, and Rafael J Gomez-Villamandos, and Jordi Muntane, and Pedro López-Cillero
Liver Research Unit, Instituto Maimónides para la Investigación Biomédica de Córdoba, Reina Sofia University Hospital, Córdoba, Spain. p.aguilar.melero@gmail.com

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011300 Preoperative Care Care given during the period prior to undergoing surgery when psychological and physical preparations are made according to the special needs of the individual patient. This period spans the time between admission to the hospital to the time the surgery begins. (From Dictionary of Health Services Management, 2d ed) Care, Preoperative,Preoperative Procedure,Preoperative Procedures,Procedure, Preoperative,Procedures, Preoperative
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D012143 Respiratory Physiological Phenomena Physiological processes and properties of the RESPIRATORY SYSTEM as a whole or of any of its parts. Respiratory Physiologic Processes,Respiratory Physiological Processes,Respiratory Physiology,Physiology, Respiratory,Pulmonary Physiological Phenomena,Pulmonary Physiological Phenomenon,Pulmonary Physiological Process,Pulmonary Physiological Processes,Respiratory Physiological Concepts,Respiratory Physiological Phenomenon,Respiratory Physiological Process,Concept, Respiratory Physiological,Concepts, Respiratory Physiological,Phenomena, Pulmonary Physiological,Phenomena, Respiratory Physiological,Phenomenas, Pulmonary Physiological,Phenomenas, Respiratory Physiological,Phenomenon, Pulmonary Physiological,Phenomenon, Respiratory Physiological,Phenomenons, Pulmonary Physiological,Phenomenons, Respiratory Physiological,Physiologic Processes, Respiratory,Physiological Concept, Respiratory,Physiological Concepts, Respiratory,Physiological Phenomena, Pulmonary,Physiological Phenomena, Respiratory,Physiological Phenomenas, Pulmonary,Physiological Phenomenas, Respiratory,Physiological Phenomenon, Pulmonary,Physiological Phenomenon, Respiratory,Physiological Phenomenons, Pulmonary,Physiological Phenomenons, Respiratory,Physiological Process, Pulmonary,Physiological Process, Respiratory,Physiological Processes, Pulmonary,Physiological Processes, Respiratory,Process, Pulmonary Physiological,Process, Respiratory Physiological,Processes, Pulmonary Physiological,Pulmonary Physiological Phenomenas,Pulmonary Physiological Phenomenons,Respiratory Physiological Concept,Respiratory Physiological Phenomenas,Respiratory Physiological Phenomenons
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006498 Hepatectomy Excision of all or part of the liver. (Dorland, 28th ed) Hepatectomies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog

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