Mild cellular infiltration, few necrosis as well as comparatively preserved lobular architecture were seen in the liver treated with IPO. In the evalua tion of the histological features of I/R injury, the IPO I/ R group had significantly lower scores of cytoplasmic despite vacuolization and massive necrosis compared with the I/ R group. L NAME abolished the protective effect of IPO post treatment with increased cytoplasmic vacuolization and hepatocellular necrosis. IPO reduces oxidative Inhibitors,Modulators,Libraries stress in liver tissues To assess the effect of IPO on oxidative stress after liver I/R, MDA and activity of superoxide dismutase were measured. Hepatic 60 min ischemia and 2 hours of reperfusion caused Inhibitors,Modulators,Libraries substantial increase in liver MDA levels and marked decrease in liver SOD activity com pared with IPO I/R group.

In the post treat ment of IPO, Inhibitors,Modulators,Libraries the liver MDA content reduced 64. 11% and liver SOD activity was elevated by 27. 68%. IPO increases NO, NOS in serum and in liver tissues To determine Inhibitors,Modulators,Libraries whether IPO have protective role through NO mediated production, we detected the contents of nitric oxide and nitric oxide synthase. Hepatic 60 min ischemia and 2 hours of reperfusion markedly reduced both the serum levels of NO, total NOS, endothelial NOS, iNOS, and pro duction of TNOS, eNOS, iNOS in liver tissues. Com pared to I/R group, IPO post treatment markedly induced NO, eNOS in serum. Although no significant difference was found in TNOS between I/R and IPO I/R group, some trends of higher TNOS levels could be seen in the IPO I/R group.

Inhibitors,Modulators,Libraries In L NAME IPO and L NAME I/R groups, the serum levels of NO, TNOS, eNOS and iNOS, production of TNOS, eNOS, iNOS in liver tissues were all decreased. These findings suggest that IPO have protective role partially through up regulating NO and iNOS. IPO induce HIF 1a and p Akt expression in liver tissues and modulates I/R induced read FAQ inflammatory signaling cascades To further assess whether the NO mediated production is associated with HIF 1alpha, we measured the protein expressions of HIF 1alpha and p Akt by western blot analysis. Western blot analysis results showed that the contents of HIF 1a in liver tissues with IPO post treated mice were significantly higher than those in the I/R group. Reports have shown that PI3K signal ing pathway is involved in HIF 1a up regulation in the relevant experiments. So we also determined whether IPO altered liver I/R induced PI3K signaling pathway activation. And Figure 5 shows changes in phosphorylation of Akt upon reperfusion. The ratios of p Akt and Akt in sham, IPO I/R, IPO I/R L, I/R, I/R L groups were as follows So IPO post treat ment markedly enhanced Akt phosphorylation at reper fusion compared to other group, corroborating the role of the PI3K/Akt pathway in the action of IPO.