Almost all the studies evaluating a possible role for CYP2E1 in ethanol hepatotoxicity have employed the intragastric infusion model of liver injury, since significant injury occurs in this model [5–8,10–12,16,17]. Most oral models of ethanol administration e.g. the typical Lieber-DeCarli model do not show the presence of significant liver injury beyond steatosis or small elevations in transaminase levels. There is clearly a need for oral models of ethanol treatment which result in the development of significant liver injury. There is also a need to evaluate the role of CYP2E1 in the actions of ethanol in oral models of ethanol administration. In the Lieber-DeCarli model, fatty liver and oxidative stress develops. These events are associated with induction of CYP2E1. However, direct evidence that CYP2E1 plays a role in the ethanol-induced fatty liver or oxidative stress in this oral model of ethanol administration is needed. Morgan and collaborators reported that in a transgenic mouse overexpressing CYP2E1, ethanol administration produced liver injury [18,19}. We recently reported that CYP2E1 plays a role in experimental fatty liver in an oral, Lieber-DeCarli ethanol feeding model [20].
