title: The effect of U-74389G on pancreas ischemia-reperfusion injury in a swine model.
abstract: BACKGROUND
  Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack. The aim of our study was to evaluate the therapeutic potential of 21-aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the organ in a swine model.
  
  
  METHODS
  Twelve pigs (weighing 28-35 kg) were randomized into the following two experimental groups: group A (control group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min; and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min. Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated measures analysis of variance was performed for the evaluation of differences between the two groups.
  
  
  RESULTS
  Histopathologic evaluation did not reveal a statistically significant difference concerning hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P = 0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P = 0.020). Serum metabolic data in the control and therapy groups were not significantly different; accordingly, tissue malondialdehyde levels (P = 0.705) and tumor necrosis factor α values (P = 0.863) did not differ between the two groups.
  
  
  CONCLUSIONS
  On the basis of the histologic data and the absence of reduction in the malondialdehyde and tumor necrosis factor α levels, it is concluded that the administration of U-74389G does not seem to exert a sizable therapeutic effect in attenuating pancreatic damage from ischemia-reperfusion injury.
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece. Electronic address: dixrys@yahoo.gr.
authors: Dimosthenis T
authors: DT
authors: Chrysikos
authors: Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, School of Medicine, Athens, Greece.
authors: Theodoros N
authors: TN
authors: Sergentanis
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece.
authors: Flora
authors: F
authors: Zagouri
authors: Department of Hygiene, Epidemiology and Medical Statistics, University of Athens, School of Medicine, Athens, Greece.
authors: Theodora
authors: T
authors: Psaltopoulou
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece.
authors: Ioannis
authors: I
authors: Flessas
authors: Department of Pathology, University of Athens, School of Medicine, Athens, Greece.
authors: George
authors: G
authors: Agrogiannis
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece.
authors: Nikolaos
authors: N
authors: Alexakis
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece.
authors: Ioannis
authors: I
authors: Bramis
authors: Department of Pathology, University of Athens, School of Medicine, Athens, Greece.
authors: Evgenia E
authors: EE
authors: Patsouri
authors: Department of Pathology, University of Athens, School of Medicine, Athens, Greece.
authors: Efstratios S
authors: ES
authors: Patsouris
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece.
authors: Maria
authors: M
authors: Korontzi
authors: Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
authors: Angeliki
authors: A
authors: Katsarou
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece.
authors: George C
authors: GC
authors: Zografos
authors: 1st Department of Propaedeutic Surgery, Hippokratio Hospital, University of Athens, School of Medicine, Athens, Greece; Experimental-Research Center, Elpen Pharmaceuticals, Athens, Greece.
authors: Apostolos E
authors: AE
authors: Papalois
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011281:Pregnatrienes / Q000494:pharmacology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D034421:Sus scrofa; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D011281:Pregnatrienes; D014409:Tumor Necrosis Factor-alpha; C074965:U 74389F; D008315:Malondialdehyde
keywords: Ischemia; Lazaroid; MDA; Pancreas; Reperfusion; TNF-α; U-74389G