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 evidence that reactive oxygen species play a role in both acute and chronic pancreatitis. In the liver, cytochrome P4502E1 (CYP2E1, the inducible ethanol metabolising enzyme) is one of the proposed pathways by which ethanol induces oxidative stress.


OBJECTIVE
To determine whether CYP2E1 is present in the pancreas and, if so, whether it is inducible by chronic ethanol feeding.


METHODS
Eighteen male Sprague-Dawley rats were pair fed liquid diets with or without ethanol as 36% of energy for four weeks. CYP2E1 levels were determined by western blotting of microsomal protein from both pancreas and liver. Messenger RNA (mRNA) levels for CYP2E1 were quantified using dot blots of total pancreatic RNA.


RESULTS
CYP2E1 was found in the pancreas. Furthermore, the amount of CYP2E1 was greater in the pancreas of rats fed ethanol compared with controls (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 similar (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 by chronic ethanol administration. Induction of pancreatic CYP2E1 is not regulated at the mRNA level. The metabolism of ethanol via CYP2E1 may contribute to oxidative stress in the pancreas during chronic ethanol consumption.
Norton
I D
ID
Department of Gastroenterology, Prince of Wales Hospital, Sydney, Australia.
Apte
M V
MV
Haber
P S
PS
McCaughan
G W
GW
Pirola
R C
RC
Wilson
J S
JS
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D000431:Ethanol; D019392:Cytochrome P-450 CYP2E1