The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model

Background/Aims: CYP2E1 metabolizes ethanol, generates reactive oxygen species, and is suggested to be important for development of alcoholic liver disease. The present study aims to evaluate the role of CYP2E1 in combination with ethanol for development of alcoholic liver disease using mice transgenic for the human CYP2E1 gene. Methods: Changes in hepatic gene expression were monitored in controls and mice transgenic for human CYP2E1, treated with ethanol or isocaloric dextrose intragastrically for 4 weeks, and related to pathology using Affymetrix microarrays and TaqMan RealTime PCR. Results: Presence of the CYP2E1 transgene increased liver injury and increased expression of stress related genes. Microarray analyses revealed the expression of structural genes, particularly cytokeratin 8 and 18, to be highly related to pathology. Conclusions: This in vivo study confirms several findings regarding CYP2E1 and alcohol previously found only in vitro. These results provide in vivo evidence that CYP2E1 overexpression aggravates hepatic injury, and suggest that expression of cytokeratins 8 and 18 can be considered as biomakers for the progression of alcoholic liver disease. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.