Ethanol complete degradation produces a large amount of reducing agents in the form of NADH (from ADH and ADLH catalyzed reactions) and NADPH (from cytochrome P4502E1) that overwhelm the hepatocyte's ability to maintain redox homeostasis. Moreover the altered redox state impairs gluconeogenesis, diverts acetyl-CoA toward ketogenesis and fatty acid synthesis, and diminishes lipid oxidation disrupting fatty acids β-oxidation [7]. Recent works indicate that reactive oxygen species play a major role in alcohol induced liver injury: CYP2E1 ethanol degradation in the presence of iron generates reactive oxygen species (ROS) thus increasing oxidative stress and leading to membrane-lipids oxidation [8], furthermore oxidative stress depletes the cell reservoir of reduced glutathione (GSH), vitamin E, and S-adenosyl methionine (SAM) [9–12]. These altered mechanisms, along with oxidative stress, are however insufficient to account for all the effects of ethanol consumption and recent works highlight the importance of nuclear receptors and transcription factors in the pathogenesis of liver disease.
