Cytochrome P4502E1 is present in rat pancreas and is induced by chronic ethanol administration
I D Norton Department of Gastroenterology, Prince of
Wales Hospital, Sydney, Australia
Correspondence to: Dr J S Wilson,
Department of Gastroenterology, Prince of Wales Hospital, High Street,
Randwick 2031, Australia. Accepted for publication 5 September 1997 Background Keywords:
cytochrome P4502E1;
rat pancreas;
chronic ethanol
administration
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.
AimsTo determine whether CYP2E1 is present in
the pancreas and, if so, whether it is inducible by chronic ethanol feeding.
MethodsEighteen 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.
ResultsCYP2E1 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.
ConclusionsCYP2E1 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.
(GUT 1998;42:426-430)
© 1998 by Gut
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