{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:33:39Z","timestamp":1790775219966,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T00:00:00Z","timestamp":1509321600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>Cytochrome P450 2E1 (<jats:italic toggle=\"yes\">CYP2E1<\/jats:italic>) plays an important role in alcohol and toxin metabolism by catalyzing the conversion of substrates into more polar metabolites and producing reactive oxygen species. Reactive oxygen species\u2010induced oxidative stress promotes hepatocyte injury and death, which in turn induces inflammation, activation of hepatic stellate cells, and liver fibrosis. Here, we analyzed mice expressing only the human<jats:italic toggle=\"yes\">CYP2E1<\/jats:italic>gene (hCYP2E1) to determine differences in hCYP2E1 versus endogenous mouse Cyp2e1 function with different liver injuries. After intragastric alcohol feeding,<jats:italic toggle=\"yes\">CYP2E1<\/jats:italic>expression was induced in both hCYP2E1 and wild\u2010type (Wt) mice. hCYP2E1 mice had greater inflammation, fibrosis, and lipid peroxidation but less hepatic steatosis. In addition, hCYP2E1 mice demonstrated increased expression of fibrogenic and proinflammatory genes but decreased expression of<jats:italic toggle=\"yes\">de novo<\/jats:italic>lipogenic genes compared to Wt mice. Lipidomics of free fatty acid, triacylglycerol, diacylglycerol, and cholesterol ester species and proinflammatory prostaglandins support these conclusions. Carbon tetrachloride\u2010induced injury suppressed expression of both mouse and human<jats:italic toggle=\"yes\">CYP2E1<\/jats:italic>, but again hCYP2E1 mice exhibited greater hepatic stellate cell activation and fibrosis than Wt controls with comparable expression of proinflammatory genes. By contrast, 14\u2010day bile duct ligation induced comparable cholestatic injury and fibrosis in both genotypes.<jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Alcohol\u2010induced liver fibrosis but not hepatic steatosis is more severe in the hCYP2E1 mouse than in the Wt mouse, demonstrating the use of this model to provide insight into the pathogenesis of alcoholic liver disease. 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