Inhibition of TNF-alpha protects against hepatic ischemia-reperfusion injury in rats via NF-kappa B dependent pathway

Hepatic ischemia-reperfusion injury (I/R) is a serious health problem associated with liver transplantation, resection surgery, and various types of shock especially hemorrhagic shock. In the present investigation, the effect of inhibition of tumor necrosis factor-alpha (TNF-alpha) using pentoxifylline or infliximab against hepatic I/R injury induced in rats by 45-min ischemia and 1-h reperfusion was studied. It was observed that both pentoxifylline and infliximab-treated groups showed a significantly lower extent and severity of liver injury. This is attributed to (1) a decrease in oxidative stress markers, (2) reduction of the expression of TNF-alpha, TNF-alpha type-1 receptors, and nuclear factor kappa B (NF-kappa B). Thus TNF-alpha inhibition may be one of the therapeutic interventions to overcome the deleterious effects of I/R on liver via reduction of oxidative stress and inhibition of inflammatory cascade.