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U-74389G Significantly Reduced TNF-α in a Swine Model of Acute Liver Ischemia-Reperfusion Injury

Periklis Zavridis, Georgios Vlachos, Anthony Lisacek-Kiosoglous, Andrew Georgiou, Maria Tsitskari, Constantinos Hadjileontis, Ioannis Patrikios, Apostolos Papalois, George Zografos and Konstantinos Toutouzas

Introduction: Ischemia-reperfusion injury (IRI) is one of the main causes of increased morbidity in hepatic surgery following portal triad clamping and blood reflow.
Aim: The aim of this study was to determine whether intraoperative administration of the lazaroid U-74389G can reduce inflammatory activity in landrace pigs undergoing hepatectomy with Pringle maneuver.
Methods: Fourteen landrace pigs (30 ± 2 kgr) were randomized into two groups: in group A (n=7) lazaroid U-74389G was administrated immediately after the Pringle maneuver was removed while in group B (control group, n=7) it was not. Blood samples were obtained at four phases: 1) before clamping 2) 30 min after clamping removal 3) two hours after hepatectomy and 4) 24 hours after hepatectomy. Quantitative analyses of the inflammatory markers IL-1β, IL-10, IFN-α, IFN-γ, TNF-α, IL-4, and IL-8 were performed. In order to histopathologically evaluate the number of neutrophils, lymphocytes, macrophages and apoptotic bodies in liver in the two groups, samples which included at least one big vessel were taken at phases 3 and 4.
Results: Histological analysis revealed the presence of inflammation and apoptosis, of the same density, in both groups. Biochemical analysis revealed a statistically significant decrease (P<0.01) of TNF-α at phases 2, 3 and 4 and of IFN-α (p= 0.02) at phase 4 in group A compared to control group.
Conclusion: Pro-apoptotic chemokine TNF-α was significantly reduced for 24 hours after the administration of antioxidant U-74389G in group A. However, the effect of U-74389G did not appear to be obvious in terms of inflammation and apoptosis in histological evaluation.