The effect of U-74389G on pancreas ischemia-reperfusion injury in a swine model

J Surg Res. 2014 Apr;187(2):450-7. doi: 10.1016/j.jss.2013.11.1082. Epub 2013 Nov 16.


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.

Materials and 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.

Keywords: Ischemia; Lazaroid; MDA; Pancreas; Reperfusion; TNF-α; U-74389G.

MeSH terms

  • Acute Disease
  • Animals
  • Antioxidants / pharmacology*
  • Disease Models, Animal
  • Female
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Pancreatitis, Acute Necrotizing / drug therapy*
  • Pancreatitis, Acute Necrotizing / metabolism
  • Pancreatitis, Acute Necrotizing / pathology
  • Pregnatrienes / pharmacology*
  • Random Allocation
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Sus scrofa
  • Treatment Failure
  • Tumor Necrosis Factor-alpha / metabolism


  • Antioxidants
  • Pregnatrienes
  • Tumor Necrosis Factor-alpha
  • U 74389F
  • Malondialdehyde