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.
Arkadopoulos
Nikolaos
N
Experimental Surgical Laboratory, Athens University School of Medicine, Aretaieion University Hospital, Athens, Greece. narkado@otenet.gr
Nastos
Constantinos
C
Kalimeris
Konstantinos
K
Economou
Emmanuil
E
Theodoraki
Kassiani
K
Kouskouni
Evangelia
E
Pafiti
Agathi
A
Kostopanagiotou
Georgia
G
Smyrniotis
Vassilios
V
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