Nuclear factor κB inactivation in the rat liver ameliorates short term total warm ischaemia/reperfusion injury

Background: In hepatic ischaemia/ reperfusion injury, activated liver macrophages ( Kupffer cells) are dominantly regulated by a transcription factor, nuclear factor kappa B ( NFkB), with respect to expression of inflammatory cytokines, acute phase response proteins, and cell adhesion molecules. Aims: We assessed whether inactivation of NFkB in the liver could attenuate total hepatic warm ischaemia/ reperfusion injury. Methods: We studied rats with hepatic overexpression of inhibitor kappa B alpha super- repressor ( I kappa B alpha SR) caused by a transgene introduced using an adenoviral vector. Hepatic ischaemia/ reperfusion injury was induced under warm conditions by total occlusion of hepatoduodenal ligament structures for 20 minutes, followed by reperfusion. Controls included uninfected and control virus ( AdLacZ) infected rats. Results: I kappa B alpha SR was overexpressed in Kupffer cells as well as in hepatocytes, blocking nuclear translocation of NF kappa B ( p65) into the nucleus after reperfusion. Gene transfection with I kappa B alpha SR, but not with LacZ, markedly attenuated ischaemia/ reperfusion injury, suppressing inducible nitric oxide synthase and nitrotyrosine expression in the liver. Moreover, no remarkable hepatocyte apoptosis was detected under I kappa B alpha SR overexpression. Conclusions: Adenoviral transfer of the I kappa B alpha SR gene in the liver ameliorates short term warm ischaemia/ reperfusion injury, possibly through attenuation of hepatic macrophage activation.