Binge-type ethanol consumption causes induction of kupffer cell cytochromeP4502E1, increased intracellular reactive oxygen species and prolonged extracellular release of superoxide after blood alcohol normalizes

Continuous intragastric infusion of alcohol in a liquid diet produces liver injury in rats. In this model, blood alcohol concentrations cyclically inc rease, then return to a lower basal level. The higher blood alcohol concent rations are associated with increased hepatic expression of cytochrome P450 2E1 (CYP2E1) and production of reactive oxygen species (ROS). Binging also produces cyclical increases in blood alcohol. To mimic this common pattern of alcohol intake in humans, we caused periodic increases in blood alcohol concentrations in rats by 5 oral gavages with 33% ethanol solution administ ered over 2.5 days (a binge) followed by 4.5 days of no alcohol before repe ating the alcohol binge. This produced intermittent high blood alcohol conc entrations. Kupffer cells (KC) from alcohol binged rats demonstrated induct ion of CYP2E1 gene expression and enhanced intracellular production of ROS and extracellular release of superoxide free radical. Treatment with chlorm ethiazole, an inhibitor of CYP2E1 gene expression, prevented the alcohol in duced increase in intracellular ROS. Extracellular release of superoxide wa s also increased by alcohol binging and remained elevated for 48 hrs after alcohol exposure was terminated.