Iron chelation for amelioration of liver ischemia-reperfusion injury.
Liver resections are frequently associated with significant ischemia-reperfusion (I-R) injury of the liver remnant. The aim of this study was to investigate whether deferoxamine (DFO) can ameliorate I-R injury during major hepatectomies performed under vascular exclusion of the liver in a porcine model. Twelve female domestic pigs were divided into control (n = 6) and DFO treatment (n = 6) groups and subjected to 150 min. liver ischemia followed by 70% hepatectomy and 24 hours reperfusion. Pigs in the DFO group received a continuous intravenous infusion of 100 mg/kg DFO. Liver remnant injury was evaluated by liver function tests, hepatic histology as well as serum and liver tissue malondialdehyde (MDA) concentrations. Deferoxamine-treated animals had reduced total bilirubin, gamma-glutamyl transferase and ammonia levels as well as hepatocyte necrosis and oxidative injury. In a subsequent randomized clinical trial using DFO for I-R protection during major liver surgery, preliminary results revealed amelioration of hepatocellular damage, oxidative and inflammatory serum markers and apoptotic response in liver remnant biopsies.
Experimental Surgical Laboratory, Athens University School of Medicine, Aretaieion University Hospital, Athens, Greece. narkado@otenet.gr
Nikolaos
N
Arkadopoulos
Constantinos
C
Nastos
Konstantinos
K
Kalimeris
Emmanuil
E
Economou
Kassiani
K
Theodoraki
Evangelia
E
Kouskouni
Agathi
A
Pafiti
Georgia
G
Kostopanagiotou
Vassilios
V
Smyrniotis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003676:Deferoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000601:surgery; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D013552:Swine
D007502:Iron Chelating Agents; D003676:Deferoxamine