Abstract
Background. Alcohol abuse is a major cause of pancreatic damage. Recent experimental evidence
suggests that fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites, injure
pancreatic acinar cells. Linkage between oxidative and nonoxidative metabolism of
ethanol in the pancreas may contribute to increased FAEE levels. Methods. To study the association between oxidative and nonoxidative ethanol metabolism, FAEE
concentration and FAEE synthase activity in rat pancreatic and liver homogenates incubated
with ethanol were evaluated with and without inhibitors of oxidative ethanol metabolism.
For toxicity studies, trypsinogen activation peptide synthesis as a measure of pancreatic
cell injury was quantitated in unstimulated and cerulein-stimulated isolated pancreatic
acinar cells incubated with ethanol or FAEE. Results. Inhibition of oxidative ethanol metabolism results in a 2- to 3-fold increase in
nonoxidative ethanol metabolism to FAEE in pancreas and in liver. Both ethanol and
FAEE induce increased intracellular trypsinogen activation by more than 50% in the
presence of physiologic concentrations of cerulein in vitro. Conclusions. These findings demonstrate that the inhibition of oxidative ethanol metabolism results
in an increase in flux through the nonoxidative pathway and support the proposition
that alcohol-induced pancreatic injury is mediated at least in part by FAEE, which
are important products of pancreatic ethanol metabolism.(Surgery 2001;129:736-44.)
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Article info
Publication history
Accepted:
December 23,
2000
Footnotes
*Reprint requests: Andrew L. Warshaw, MD, Surgeon-in-Chief, Chairman, Department of Surgery, W. Gerald Austen Professor of Surgery, Massachusetts General Hospital, Room 506, White Building, 55 Fruit St, Boston, MA 02114.
**Surgery 2001;129:736-44.
Identification
Copyright
© 2001 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
