Pancreatic injury in rats induced by fatty acid ethyl ester, a nonoxidative metabolite of alcohol.
OBJECTIVE
The mechanism by which alcohol injures the pancreas remains unknown. Alcohol-intoxicated humans have high levels of fatty acid ethyl esters (FAEEs), nonoxidative products of ethanol metabolism, in blood, pancreas, and liver. The aims of this study were to determine whether FAEEs are toxic to the pancreas in vivo and, if so, to assess whether this injury is specific to the pancreas and to compare it to the injury observed in acute pancreatitis.


METHODS
FAEEs were infused into Sprague-Dawley rats. Levels of FAEEs in plasma and pancreas were measured, and pancreatic injury was assessed during a 48-hour period for edema formation and ectopic trypsinogen activation and by light and electron microscopy.


RESULTS
FAEEs induced highly significant increases in pancreatic edema, pancreatic trypsinogen activation, and vacuolization of acinar cells. These findings were specific to the pancreas and were not found in liver, lung, myocardium, skeletal muscle, or subcutaneous fat.


CONCLUSIONS
FAEEs at concentrations found in human plasma produce a pancreatitis-like injury in rats, providing direct evidence that FAEEs can produce organ-specific toxicity. Thus, FAEEs may contribute to acute alcohol-induced damage to the pancreas.
Werner
J
J
Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Laposata
M
M
Fernández-del Castillo
C
C
Saghir
M
M
Iozzo
R V
RV
Lewandrowski
K B
KB
Warshaw
A L
AL
D000818:Animals; D002788:Cholesterol Esters / Q000633:toxicity*; D000431:Ethanol / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008854:Microscopy, Electron; D010169:Palmitic Acids / Q000633:toxicity*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019512:Pancreatitis, Alcoholic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014362:Trypsinogen / Q000378:metabolism
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D010169:Palmitic Acids; D000431:Ethanol; D014362:Trypsinogen; C007680:ethyl palmitate; C026651:cholesteryl palmitate