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. 1998 Mar;42(3):426–430. doi: 10.1136/gut.42.3.426

Cytochrome P4502E1 is present in rat pancreas and is induced by chronic ethanol administration

I Norton 1, M Apte 1, P Haber 1, G McCaughan 1, R Pirola 1, J Wilson 1
PMCID: PMC1727026  PMID: 9577353

Abstract

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. 
Aims—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. 



Keywords: cytochrome P4502E1; rat pancreas; chronic ethanol administration

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Figure 1 .

Figure 1

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Representative western blot of pancreatic microsomal protein showing the presence of cytochrome P4502E1 in control pancreas and induction of this protein due to chronic ethanol administration. 


Figure 2 .

Figure 2

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Representative western blot of hepatic microsomal protein showing the presence of cytochrome P4502E1 in control liver and induction of this protein due to chronic ethanol administration. 


Figure 3 .

Figure 3

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Induction of CYP2E1 in pancreas and liver of rats fed ethanol. Results expressed as x fold increase over control, calculated from arbitrary densitometer units per µg of microsomal protein. n=9 pairs. *p<0.02, †p<0.005 compared with control. 


Figure 4 .

Figure 4

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Representative western blot comparing the induction of CYP2E1 in the pancreas and liver during chronic ethanol exposure. 


Figure 5 .

Figure 5

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Representative autoradiographs of northern blots for β actin and P4502E1 mRNA showing specificity of the probes. 


Figure 6 .

Figure 6

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Representative autoradiographs of RNA dot blots from control (C) and ethanol fed (E) animals. 


Figure 7 .

Figure 7

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Comparison of CYP2E1 mRNA dot blots, determined by microchannel array detection. n=8 pairs (NS). 


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