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- W1175442906 abstract "Introduction Experimental alcohol-induced liver injury is exacerbated by a high polyunsaturated fat diet rich in linoleic acid (LA). The aim of the study was to evaluate the role of bioactive oxidized LA metabolites (OXLAMs) and their signaling through the Transient Receptor Potential Vanilloid 1 (TRPV1) in an experimental animal model of alcoholic liver disease (ALD). Methods C57BL/6 wild type (WT) and Trpv1 knock out mice were fed a diet containing 5% ethanol for 10 days, followed by a single ethanol gavage. Liver steatosis, injury and inflammation were assessed. In vitro studies using HepG2 cells were performed to evaluate OXLAM/TRPV1 signaling. Results Chronic-binge alcohol administration to WT animals resulted in a marked increase in plasma OXLAM levels, specifically 9- and 13-HODEs, in parallel with the up-regulation of hepatic Trpv1. These effects were associated with hepatic steatosis, inflammation and injury. Genetic depletion of Trpv1 did not blunt hepatic steatosis caused by EtOH, but ameliorated hepatic injury and prevented the increase in pro-inflammatory cytokine and chemokine expression, including Tnf-α, IL-6, Mip-2, Mcp1, and Pai-1. Exposure of HepG2 cells to 9- and 13-HODEs resulted in activation of TRPV1 signal transduction with the increased intracellular Ca2+ levels, suggesting that OXLAM/TRPV1/Ca2+ signaling may be a relevant pathway contributing to ALD. Conclusions TRPV1-OXLAM interactions appear to play a significant role in ethanol-induced hepatic inflammation/injury, further supporting an important role for dietary lipids in ALD." @default.
- W1175442906 created "2016-06-24" @default.
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- W1175442906 date "2015-04-01" @default.
- W1175442906 modified "2023-09-23" @default.
- W1175442906 title "Chronic‐Binge Alcohol‐Induced Hepatic Injury and Inflammation Were Ameliorated in Mice Deficient for Transient Receptor Potential Vanilloid 1 Gene" @default.
- W1175442906 doi "https://doi.org/10.1096/fasebj.29.1_supplement.1020.6" @default.
- W1175442906 hasPublicationYear "2015" @default.
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