PULSATILE BLOOD-ALCOHOL AND CYP2E1 INDUCTION DURING CHRONIC ALCOHOL INFUSIONS IN RATS

Adult male Sprague-Dawley rats were treated with alcohol for 35 days u sing a total enteral nutrition model. Intragastric cannulae were inser ted into rats and they were infused with a diet designed to promote no rmal growth in male rats. Alcohol was infused at 35% of total calories for 35 days. Urine and blood alcohol concentrations were determined a nd found to be pulsatile during continuous alcohol infusion, having va lues between near zero and greater than 500 mg/dl. Twenty-four-hour ur ine alcohol concentrations were found to be excellent indicators of bl ood alcohol concentrations (BACs). Cytochrome P450 CYP2E1 was induced in a two-step manner. Step one occurred at BACs below 250 mg/dl and wa s characterized by significant (p less than or equal to 0.05) elevatio ns in activities and apoprotein levels with no changes in steady-state mRNA. Step two occurred with BACs greater than 300 mg/dl and resulted in significant (p less than or equal to 0.05) elevations in steady-st ate mRNA levels. We propose that the pulsatile BACs are caused by an e thanol concentration-dependent regulation of an ethanol metabolizing s ystem, perhaps CYP2E1.