CYTOCHROME P4502E1 IS PRESENT IN RAT PANCREAS AND IS INDUCED BY CHRONIC ETHANOL ADMINISTRATION

Background-The mechanisms responsible for the initiation of alcoholic pancreatitis remain elusive. However, there is an increasing body of e vidence that reactive oxygen species play a role in both acute and chr onic pancreatitis. In the liver, cytochrome P4502E1 (CYP2E1, the induc ible ethanol metabolising enzyme) is one of the proposed pathways by w hich ethanol induces oxidative stress. Aims-To determine whether CYP2E 1 is present in the pancreas and, if so, whether it is inducible by ch ronic ethanol feeding. Methods-Eighteen male Sprague-Dawley rats were pair fed Liquid diets with or without ethanol as 36% of energy for fou r weeks. CYP2E1 levels were determined by western blotting of microsom al protein from both pancreas and liver. Messenger RNA (mRNA) levels f or CYP2E1 were quantified using dot blots of total pancreatic RNA. Res ults-CYP2E1 was found in the pancreas. Furthermore, the amount of CYP2 E1 was greater in the pancreas of rats fed ethanol compared with contr ols (mean increase over controls 5.1-fold, 95% confidence intervals 2. 4 to 7.7, p<0.02). In the liver, induction by ethanol of CYP2E1 was si milar (mean increase over controls 7.9-fold, 95% confidence intervals 5.2 to 10.6, p<0.005). Pancreatic mRNA levels for CYP2E1 were similar in ethanol fed and control rats. Conclusions-CYP2E1 is present in the rat pancreas and is inducible bg chronic ethanol administration. Induc tion of pancreatic CYP2E1 is not regulated at the mRNA level. The meta bolism of ethanol via CYP2E1 may contribute to oxidative stress in the pancreas during chronic ethanol consumption.