Livers were harvested upon sacrifice to study lipid profiles in relation to histopathology and molecular indices of insulin resistance, inflammation, and stress. Frozen liver sections were mounted on indium tin oxide coated glass slides and coated with matrix (2,5-dihydroxybenzoic acid) by sublimation. Lipids were analyzed with MALDI-TOF and stained with H&E. Adjacent sections were stained with H&E and Oil Red O. Results: Chronic-binge ethanol exposures produced striking steatohepatitis Selleck NVP-BGJ398 with hepatocellular necrosis, apopto-sis, degeneration, loss of normal chord architecture, and

early fibrosis. These abnormalities were associated with diffuse accumulations of lipids (m/z 798.1 and 820.1) as visualized by MALDI. NNK caused steatohepatitis with prominent oxidative injury and O6-methyl-Guanine DNA adducts.

NNK associated MALDI images were distinct from those of ethanol and control rats. Combined ethanol+NNK exposures caused severe hepa-tocellular injury and degeneration with steatohepatitis, fibrosis, and architectural disarray. MALDI images were composites of ethanol and NNK effects. Conclusions: IMS is an important new approach that could help characterize the biochemical pathology of steatohepatitis and distinguish effects of different etiologic agents. This would improve our understanding of disease pathogenesis. Disclosures: Shannon Cornett – Employment: Bruker Corp The following people have nothing to disclose: Emine Yalcin, Kavin M. Nunez, Ming Tong, Suzanne M. de la Monte Background: NLRP3 inflammasome activation 3-deazaneplanocin A order appears to induce many alcohol-related consequences in animal model of Alcoholic Liver Disease (ALD), but little is known about their inflammasome MCE modulation in human alcoholic liver cirrhosis. Oxidized linoleic acid metabolites (OXLAMs), the pleiotropic bioactive derivatives of linoleic acid (LA), have been implicated in a variety of pathological conditions. Circulating OXLAMs including 9-HODE comprise

a family of endogenous transient receptor potential vanilloid 1 (TRPV1) agonists. The TRPV1 is known to be present in neurogenic inflammation, but its role in the activation of the peripheral NLPR3 inflammasome has not been investigated. We used synthetic OXLAMs, and TRPV1 antagonists and agonists to test the role of TRPV1 activation in peripheral inflammation. Methods: The NLRP3 inflammasome was activated by LPS (100ng/ml) and ATP (2mM) in PBMCs of healthy controls or alcoholic liver cirrhosis patients (Inclusion/ Exclusion: clinical evidence of liver cirrhosis, Child-Pugh score A or B, No HCV, No HBV, No HIV, No h/o recent infection, No hospitalization within 28 days, No suspicion of any cancer, No history of severe chronic disease, No pregnancy, Cre-atinine < 1.5, No hepatic encephalopathy) in the presence and absence of the synthetic OXLAMs, TRPV1 antagonists and agonists.