Linkage of oxidative and nonoxidative ethanol metabolism in the pancreas and toxicity of nonoxidative ethanol metabolites for pancreatic acinar cells

Citation
J. Werner et al., Linkage of oxidative and nonoxidative ethanol metabolism in the pancreas and toxicity of nonoxidative ethanol metabolites for pancreatic acinar cells, SURGERY, 129(6), 2001, pp. 736-744
Citations number
53
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Surgery,"Medical Research Diagnosis & Treatment
Journal title
SURGERY
ISSN journal
0039-6060 → ACNP
Volume
129
Issue
6
Year of publication
2001
Pages
736 - 744
Database
ISI
SICI code
0039-6060(200106)129:6<736:LOOANE>2.0.ZU;2-R
Abstract
Background. Alcohol abuse is a major cause of pancreatic damage. Recent exp erimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidati ve ethanol metabolites, injure pancreatic acinar cells. Linkage between oxi dative and nonoxidative metabolism of ethanol in the pancreas may contribut e to increased FAEE levels. Methods. To study the association between oxidative and nonoxidative ethano l metabolism, FAEE concentration and FAEE synthase activity in rat pancreat ic and liver homogenates incubated with ethanol were evaluated with and wit hout inhibitors of oxidative ethanol metabolism. For toxicity studies, tryp sinogen activation peptide synthesis as a measure of pancreatic cell injury was quantitated in unstimulated and cerulein-stimulated isolated pancreati c acinar cells incubated with ethanol or FAEE. Results. Inhibition of oxidative ethanol metabolism results in a 2- to 3-fo ld increase in nonoxidative ethanol metabolism to FAEE in pancreas and in l iver. Both ethanol and FAEE induce increased intracellular trypsinogen acti vation by more than 50% in the presence of physiologic concentrations of ce rulein in vitro. Conclusions. These findings demonstrate that the inhibition of oxidative et hanol metabolism results in an increase in flux through the nonoxidative pa thway and support the proposition that alcohol-induced pancreatic injury is mediated at least in part by FAEE, which are important products of pancrea tic ethanol metabolism.