Disclosures: The

following people have nothing to disclose: Guohua Lou, Yanning Liu, Zhi Chen BACKGROUND: ALR is a sulfhydryl oxidase enzyme present (1) in all mammalian tissues. We reported its anti-apoptotic and anti-oxidative activity both, in vivo, (2) and, in vitro (3), in neo-plastic glioma cells treated with specific ALR siRNA. In both experimental models, we demonstrated that ALR is a key factor for the maintenance of cell survival (apoptosis) cellular nor-moxic state control and for mitochondrial membrane integrity. AIM: To evaluate the biological effects of ALR on hepatocyte apoptosis and proliferation by reducing ALR expression EPZ-6438 supplier in hepatic tissue of PH rats. MATERIALS AND METHODS: Seventy

percent PH rats were administered, just after the surgery, with adenovirus-carrying ALR shRNA (AD-shRNA) and followed for 48 hours. At the time of the sacrifice (12, 24, 48 hours after PH), polyamine levels, ALR expression (Western Blot analysis), cell proliferation (BrdU+ and mitotic index) and apoptosis (Bcl-2, Bax and activated caspase 3) and liver mass recovery were evaluated on hepatic tissue. Liver cell toxicity was determined by ALT serum levels and by histology. PH rats injected with adeno-LacZ were used as control. RESULTS: The AD-shRNA treatment did not show any cell toxicity. A statistically significant reduction of ALR expression was demonstrated at 12 and 24 hours after PH with a parallel decrease of hepatocyte proliferation and polyamine

synthesis. In liver tissue of AD-shRNA treated rats, a decrease of anti-apoptotic factors (Bcl-2) and an increase of pro-apoptotic factors Fulvestrant solubility dmso (activated caspase 3 and Bax) was observed. At 24 hr after partial hepatectomy, there were major expression differences in ALR protein and mitotic index, comparing rats treated and not treated with AD-shRNA: AD-shRNA treated: ALR:actin 4.7 mitotic index 0.003 % Controls: ALR:actin 10.7 mitotic index 0.8% CONCLUSION: Our data confirm that abolishing ALR expression in vivo in 70% PH rats there is a complete change in the physiological state of hepatocytes see more with prevalence of apoptosis, increase of reactive oxygen species induced by surgery, decrease of polyamine synthesis, all parameters necessary for a correct liver mass regeneration after 70% PH confirming the physiological importance of ALR in the first phase of liver regeneration. References: (1) Francavilla A. et al. Hepatology 1 994 (2) Polimeno L. et al. Free Rad. Res. 201 1 (3) Polimeno L. etal. Cell Death Dis. 2012 Disclosures: The following people have nothing to disclose: Antonio Francavilla, Barbara Pesetti, Angela Tafaro, Giusy Bianco, Francesco Russo, Michele Linsalata, Lorenzo Polimeno Introduction: Recombinant adenoviruses (rAd) are the most common vectors used in clinical trials for gene therapy. Systemic administration of rAd show prominent tropism for liver.