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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Aldehyde Dehydrogenase, Animals, Blotting, Western, Central Nervous System Depressants, Chromatography, High Pressure Liquid, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Ethanol, Follow-Up Studies, Gene Expression, Immunohistochemistry, In Situ Nick-End Labeling, Isoenzymes, Liver, Liver Cirrhosis, Alcoholic, Liver Cirrhosis, Experimental, Liver Failure, Acute, Male, Mice, Mice, Inbred C57BL, NF-E2-Related Factor 2, Oxidative Stress, RNA, Retinal Dehydrogenase, Reverse Transcriptase Polymerase Chain Reaction, Sterol Regulatory Element Binding Protein 1, Transaminases.
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Does nuclear factor-eythroid 2-related factor 2 prevent alcohol-induced fulminant liver injury? Context: The transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2(-/-)) is essential for protecting cells against xenobiotic and oxidative stress. Increased oxidative stress has been implicated in the pathophysiology of many diseases including ethanol-induced liver disease. Therefore, the role of Nrf2(-/-) in ethanol-induced liver injury was investigated. Wild-type and Nrf2(-/-) mice were fed with the ethanol diet, followed by examination of liver pathology, mortality, and ethanol metabolism. Nrf2(-/-) mice displayed a dramatically increased mortality associated with liver failure when fed doses of ethanol that were tolerated by WT mice. Nrf2(-/-) mice showed a significantly reduced ability to detoxify acetaldehyde, leading to an accumulation of the toxic metabolite. Loss of Nrf2(-/-) caused a marked steatosis in livers of ethanol-fed mice, and Srebp1 was identified as a candidate transcription factor responsible for lipogenic enzyme induction. Furthermore, ethanol consumption led to a progressive depletion of total and mitochondrial reduced glutathione, which was associated with more pronounced structural and functional changes to mitochondria of Nrf2(-/-) mice. In addition, ethanol feeding elicited an aggravated inflammatory response mediated by Kupffer cells in Nrf2(-/-) mice as shown by an increased tumor necrosis factor-alpha secretion and activation of the interleukin-6/Stat-3 pathway. Together these changes lead to a vicious cycle of accumulating hepatocellular damage, ultimately leading to liver failure and death of Nrf2(-/-) mice.
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Our data establish a central role for Nrf2(-/-) in the protection against ethanol-induced liver injury. Final Decision: yes