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Ethanol Administration to Cystic Fibrosis Knockout Mice Results in Increased Fatty Acid Ethyl Ester Production
Author(s) -
Blanco Paola G.,
Salem Raneem O.,
Ollero Mario,
Zaman Munir M.,
CluetteBrown Joanne E.,
Freedman Steven D.,
Laposata Michael
Publication year - 2005
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000187593.86202.e8
Subject(s) - ethanol , ethyl ester , cystic fibrosis , knockout mouse , chemistry , fatty acid , medicine , pharmacology , endocrinology , biochemistry , gene , organic chemistry
A bstract : 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.