The aim of this study was to determine whether nuclear factor-κB (NF-κB) inhibitors are efficient against hepatic ischemia/reperfusion (I/R) injury. We previously demonstrated that xanthine oxidase-derived reactive oxygen species activate NF-κB during ischemia. However, the role of NF-κB activation during ischemia in post-reperfusion injury remains unclear. Therefore, while we examined the effects of NF-κB inhibitors, sulfasalazine and pyrrolidinedithiocarbamate on hepatic I/R injury using a rat lobar hepatic I/R model, we estimated the relationship between NF-κB activation during ischemia and following hepatic damage caused by reperfusion. The portal vein and the hepatic artery were clamped for 1 hr followed by reperfusion for up to 24 hr. NF-κB activation was determined by Western blot analysis. NF-κB activation was observed in the ischemic lobe of the liver, and the activation was prevented by pre-administration with NF-κB inhibitors. Although the serum ALT level, hepatic MPO activity and BSP clearance, as an index of hepatic injury, were increased after reperfusion, the increase was attenuated by pre-administration with NF-κB inhibitors. These findings suggest that NF-κB activation during ischemia is relevant to hepatic I/R injury. Moreover, we first showed that pre-administration with NF-κB inhibitors is effective against hepatic I/R injury.
2005 The Japanese Society of Toxicology