4±7.3%, p<0.01) and ALT levels (−46.2±7.3%, p<0.05); decreased intrahepatic caspase 3 activity (−50.2±25.2%, p<0.05) and levels of cleaved caspase 3 protein (−51.0±25.3%, p<0.05). Furthermore, the intensity of necrosis was decreased in the left ischemic lobes of OAA-treated animals (histological scoring; p<0.05). As expected, the increase in tissue AMP levels characteristic of energy crisis was reduced by 31.6± 9.0% (p<0.001) in the left liver lobes, whereas the energy bearing nucleotide contents were both significantly increased (ATP: +71.7±22.3%, p<0.05; ADP: +40.4±7.4%, p<0.05). The final selleck kinase inhibitor result

was an increase in the energy charge of the ischemic lobes by 52.2±22.3% (p<0.05) with OAA treatment. Conclusion: We have demonstrated that administration of oxaloacetic acid considerably reduces cell death and the extent of liver injury caused by warm ischemia in vivo and that this protective effect is associated with a significant improvement in tissue energy status. Disclosures: Marc Bilodeau - Advisory Committees or Review

Panels: Oncozyme, Bayer, Astellas; Consulting: GSK; Grant/Research Support: Merck, Synageva; Speaking and Teaching: Merck, Vertex, Abbvie, Aptalis, click here Roche The following people have nothing to disclose: Gregory Merlen, Benoit Lacoste, BenoTt Dupont, Valerie-Ann Raymond Background: Alcohol consumption exacerbates the course and outcomes of HCV-infection and reduces responsiveness to recombinant interferon alpha (IFNa) and direct antiviral treatments. The goal of this study was to examine the effects of the major ethanol metabolite, acetaldehyde (Ach) on IFNa induced signaling pathway in HCV-permissive

Huh7.5 cells. Since these cells do not metabolize ethanol, we used Ach-generating system (AGS) that employs yeast alcohol dehydrogenase and ethanol and continuously generates Ach at levels similar to ethanol-metabolizing liver cells. Methods: Ach in the medium was measured by gas chromatography (GC). IFNa signaling was determined by STAT1 phosphorylation CYTH4 (Western blot), translocation of pSTAT1 from cytosol to nucleus, immunoprecipitation of protein-protein complexes, attachment of pSTAT1 to DNA (DNA ELISA) and expression of antiviral factor, 2′5′-oligoadenylate synthetize-like (OASL) protein, a product of interferon-sensitive genes (ISGs). Results: We found that pSTAT1/STAT1 ratio was decreased in infected Huh 7.5 cells, and Ach exposure further suppressed it. These changes were not attributed to the up-regulation of inhibitors of upstream STAT1 signaling, SOCS1 and SOCS3. The trans-location of pSTAT1 from the cytosol to the nucleus was not impaired, but Ach enhanced the association between STAT1 and protein inhibitor of activated STAT1 (PIAS1), a downstream signaling inhibitor that prevented the attachment of STAT1 to DNA.