IRON CHELATION FOR AMELIORATION OF LIVER ISCHEMIA-REPERFUSION INJURY

被引:32
作者
Arkadopoulos, Nikolaos [1 ]
Nastos, Constantinos
Kalimeris, Konstantinos [2 ]
Economou, Emmanuil [3 ]
Theodoraki, Kassiani [4 ]
Kouskouni, Evangelia [3 ]
Pafiti, Agathi [5 ]
Kostopanagiotou, Georgia [2 ]
Smyrniotis, Vassilios
机构
[1] Univ Athens, Sch Med, Dept Surg 2, Aretaie Univ Hosp,Expt Surg Lab, Athens 11528, Greece
[2] Univ Athens, Sch Med, Dept Anesthesiol 2, Attikon Univ Hosp, Athens 11528, Greece
[3] Univ Athens, Sch Med, Biopathol Lab, Aretaie Univ Hosp, Athens 11528, Greece
[4] Univ Athens, Sch Med, Dept Anesthesiol 1, Aretaie Univ Hosp, Athens 11528, Greece
[5] Univ Athens, Sch Med, Dept Pathol, Aretaie Univ Hosp, Athens 11528, Greece
关键词
Chelators; Deferoxamine (DFO); Hepatectomy; Malondialdehyde (MDA); Liver necrosis; Bilirubin; Ammonia; OXIDATIVE STRESS; DESFERRIOXAMINE; ISCHEMIA/REPERFUSION; ANTIOXIDANTS; PROTECTION; QUERCETIN; SURVIVAL; FAILURE; RATS;
D O I
10.3109/03630269.2010.484766
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:265 / 277
页数:13
相关论文
共 21 条
[1]
Iron chelation attenuates intracranial pressure and improves survival in a swine model of acute liver failure [J].
Arkadopoulos, Nikolaos ;
Vlhakos, Demetrios ;
Kostopanagiotou, Georgia ;
Panagopoulos, Dimitrios ;
Karvouni, Eleni ;
Routsi, Christina ;
Kalimeris, Konstantinos ;
Andreadou, Ioanna ;
Kouskouni, Evangelia ;
Smyrniotis, Vassilios .
LIVER TRANSPLANTATION, 2008, 14 (08) :1116-1124
[2]
The role of metals in ischemia/reperfusion injury of the liver [J].
Arora, AS ;
Gores, GJ .
SEMINARS IN LIVER DISEASE, 1996, 16 (01) :31-38
[3]
Assessment of microvascular integrity in the isolated perfused rat liver by contrast-enhanced MRI. Attenuation of reperfusion injury by conjugated deferoxamine [J].
Colet, JM ;
Cetiner, E ;
Hedlund, BE ;
Muller, RN .
MAGNETIC RESONANCE IN MEDICINE, 1996, 36 (05) :753-757
[4]
DESFERAL ATTENUATES TNF RELEASE FOLLOWING HEPATIC ISCHEMIA/REPERFUSION [J].
COLLETTI, LM ;
REMICK, DG ;
CAMPBELL, DA .
JOURNAL OF SURGICAL RESEARCH, 1994, 57 (04) :447-453
[5]
IRON CHELATION IN MYOCARDIAL PRESERVATION AFTER ISCHEMIA-REPERFUSION INJURY - THE IMPORTANCE OF PRETREATMENT AND TOXICITY [J].
DEBOER, DA ;
CLARK, RE .
ANNALS OF THORACIC SURGERY, 1992, 53 (03) :412-418
[6]
Endosomal and lysosomal effects of desferrioxamine: Protection of HeLa cells from hydrogen peroxide-induced DNA damage and induction of cell-cycle arrest [J].
Doulias, PT ;
Christoforidis, S ;
Brunk, UT ;
Galaris, D .
FREE RADICAL BIOLOGY AND MEDICINE, 2003, 35 (07) :719-728
[7]
DRUGAS GT, 1991, CIRC SHOCK, V34, P278
[8]
Oxidative stress in hepatic ischemia-reperfusion injury: The role of antioxidants and iron chelating compounds [J].
Galaris, D. ;
Barbouti, A. ;
Korantzopoulos, P. .
CURRENT PHARMACEUTICAL DESIGN, 2006, 12 (23) :2875-2890
[9]
Galaris D, 2008, CRIT REV CL LAB SCI, V45, P1, DOI [10.1080/10408360701713104, 10.1080/10408360701713104 ]
[10]
Mechanism of cell death during warm hepatic ischemia-reperfusion in rats: Apoptosis or necrosis? [J].
Gujral, JS ;
Bucci, TJ ;
Farhood, A ;
Jaeschke, H .
HEPATOLOGY, 2001, 33 (02) :397-405