EN
Liver ischaemia and reperfusion (IR) injury is a significant clinical problem. The aim of our study was to investigate the protective effect of tumor necrosis factor-alpha (TNF-) on rat liver ischaemia-reperfusion injury. A TNF- dose of 3 µg/kg body weight was injected into rats that had undergone partial (70%) ischaemia and reperfusion. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total blood antioxidant level (using the FRAP test), and the concentrations of TNF-, myeloperoxidase (MPO) and malondialdehyde (MDA) in liver homogenates after 1, 6, and 72 hours of reperfusion were measured. It was demonstrated that, rats subjected to IR, the administration of small doses of TNF- significantly reduced ALT and AST activities after 60- minute liver ischaemia and 1 or 6 hour of reperfusion. The strongest reductions in ALT and AST activities were seen after 1 hour of reperfusion (30% and 35%, respectively). Exogenous TNF- reduced the release of this cytokine in all observed periods, with the greatest reduction observed after 1 hour of reperfusion. Decreases in MPO concentration (by 40-45% in all periods of observation), as a marker of hepatic neutrophil infiltration, and in MDA concentration, the end-product of lipid peroxidation (by 55-60% at all time points), accompanied the reduction of TNF- release. The administration of TNF- to the rats after IR did not alter total plasma antioxidant potential, as assayed by the FRAP test, after 1 hour of reperfusion; however, at the later times a marked increase (~ 40-50%) occurred. We demonstrated that intraperitoneal injections of small doses of TNF- protect rat livers from IR injury. The mechanism of this protection is related to reductions in the release of TNF- during IR after injection of this cytokine, resulting in reductions in oxidative stress and inflammation during the later phase of reperfusion.