Up regulation of IL-6 by ischemic preconditioning in normal and fatty rat livers: association with reduction of oxidative stress

Abstract

We analyzed the role of IL-6 in the protection that ischemic preconditioning (IP) exerts against hepatic ischemia reperfusion-mediated (I/R) oxidative damage, particularly in fatty livers. IP-related IL-6 up-regulation during reperfusion in steatotic and non-steatotic livers was correlated with reduced indexes of liver damage, as also demonstrated by pharmacol. modulation of IL-6. IP activated NF-kB and HSF during ischemia (Isc), whereas AP-1 activity was unaffected. IP blunted the activation of STAT3 and stress-responsive genes, such as NF-kB, AP-1 and heme oxygenase (HO-1) during reperfusion. The role of reduced oxidative stress in hepatoprotection of fatty livers was further demonstrated by the fact that: (i) IP prevented the decrease of glutathione levels and the increase of lipid peroxidn.; (ii) the anti-oxidant GSH-ester prevented lipid peroxidn. and necrosis. In conclusion, IP modulates the activity of transcription factors and triggers IL-6 prodn.; this may prevent hepatic I/R damage in a oxidative stress-dependent way, particularly in fatty livers