CYP2E1-dependent oxidative stress and toxicity: role in ethanol-induced liver injury.
Ethanol-induced oxidative stress plays a major role in the mechanisms by which ethanol causes liver injury. Many pathways contribute to how ethanol induces a state of oxidative stress. One central pathway appears to be the induction, by ethanol, of the CYP2E1 form of cytochrome P450 enzymes. CYP2E1 is of interest because it metabolises and activates many toxicological substrates, including ethanol, to more reactive products. Levels of CYP2E1 are elevated under a variety of physiological and pathophysiological conditions. CYP2E1 is an effective generator of reactive oxygen species. This review summarises some of the biochemical and toxicological properties of CYP2E1, and briefly describes the use of HepG2 cell lines in assessing the actions of CYP2E1. Future directions, which may help to better understand the actions of CYP2E1 and its role in alcoholic liver injury, are suggested.
Jimenez-Lopez
Jose M
JM
Mount Sinai School of Medicine, Department of Pharmacology and Biological Chemistry, New York, NY 10029, USA.
Cederbaum
Arthur I
AI
D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000502:physiology*; D004790:Enzyme Induction; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D018384:Oxidative Stress; D011110:Polymorphism, Genetic
D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1