Changes In TNF-Alpha Levels, Microcirculation Status, And Oxidation Products After Liver Ischemia/Reperfusion Injury In Mice

Abstract

Purpose: Experimental study to determine the role of TNF-α in the pathogenesis of oxidative damage in the liver induced by ischaemia reperfusion. Methods: 50 Wistar rats in five groups of 10 each, whose livers were subjected to 30 and 60 min of no-flow ischaemia followed by reperfusion for up to 60 min, by occluding blood supply to the left lateral and medial lobes of the liver, and reperfusion was instituted by releasing the occlusion. TNF-α, MPO, PNP, MDA, SGPT and LDH were measured. For the estimation of blood flow in the microcirculation was used the laser-Doppler flowmetry. Results: Ischaemia of the liver produced an increase two fold in myeloperoxidase activity (MPO), reperfusion produced five fold increase in tumor necrosis factor α, one and a half fold increase in purine nucleoside phosphorylase activity (P.N.P.). Neutrophils after reperfusion were found three fold increased in the liver tissue and the S.G.P.T. and L.D.H were found five and four fold increased respectively. The mean blood flow in the microcirculation during reperfusion period was decreased by 36.8%. Malonyldialdehyde (MDA) was statistically significant elevated after reperfusion. Conclusion: The development of delayed perfusion failure in the hepatic microcirculation during reperfusion has been documented by laser-Doppler flowmetry. The longer the ischemic episode, the more severe the microcirculatory disturbance during reperfusion. The PNP, SGPT, LDH are reliable markers of liver function and LDH found to be more sensitive in representing liver injury. Neutrophil accumulation has been documented first by the microscopic findings and also by the elevation of the MPO. Oxidative stress also seems to play an important role in liver cell damage as it is evidence by the elevation of MDA. TNF-α was found to be elevated five fold and seems to be a potent level depended activator of neutrophils and his modulation may serve as a potential target for therapeutic intervention.