Ethanol administration to cystic fibrosis knockout mice results in increased fatty acid ethyl ester production

Paola G. Blanco, Raneem O. Salem, Mario Ollero, Munir M. Zaman, Joanne E. Cluette-Brown, Steven D. Freedman, Michael Laposata

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: Fatty acid ethyl esters (FAEE) are nonoxidative ethanol metabolites shown to produce toxic effects in the liver and pancreas in vivo and in vitro. Because alcohol-induced chronic pancreatitis is associated with mutations in the gene responsible for cystic fibrosis (CFTR), we hypothesized that CFTR dysfunction leads to increased levels of these toxic nonoxidative ethanol metabolites following alcohol administration. Methods: Cystic fibrosis (CF) and wild-type (WT) mice were injected intraperitoneally with 1, 2, or 3 g/kg of 50% ethanol. Mice were sacrificed and the liver and pancreas removed for FAEE analysis. Results: The mean FAEE concentration (pmol/g) detected in the liver of cftr-/- mice following injection with 2 g/kg of ethanol was significantly greater than the amount detected in WT (p < 0.005). A similar trend in FAEE concentration was seen in the pancreas, but the difference was not statistically different. In both the liver and pancreas, analysis of individual FAEE species demonstrated a selective increase in ethyl oleate. Conclusion: These data show an association between CFTR dysfunction and qualitative and quantitative changes in FAEE in liver and pancreas upon ethanol exposure.

Original languageEnglish (US)
Pages (from-to)2039-2045
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume29
Issue number11
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Keywords

  • Alcohol
  • CFTR
  • Fatty Acids
  • Lipids

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

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