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


CONCLUSIONS
These data show an association between CFTR dysfunction and qualitative and quantitative changes in FAEE in liver and pancreas upon ethanol exposure.
Blanco
Paola G
PG
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Salem
Raneem O
RO
Ollero
Mario
M
Zaman
Munir M
MM
Cluette-Brown
Joanne E
JE
Freedman
Steven D
SD
Laposata
Michael
M
D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004952:Esters / Q000032:analysis / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D005227:Fatty Acids / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018181:Mice, Inbred CFTR; D018345:Mice, Knockout; D009154:Mutation; D009829:Oleic Acids / Q000032:analysis / Q000378:metabolism; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D019512:Pancreatitis, Alcoholic / Q000378:metabolism
D004952:Esters; D005227:Fatty Acids; D009829:Oleic Acids; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000431:Ethanol; C033180:ethyl oleate