Fatty acid ethyl esters and ethanol-induced pancreatitis.
Conjugation of xenobiotic alcohols with endogenous fatty acids is considered one of the mechanisms of their retention in the target organs. A number of fatty acid esters of alcohol's detected in the human tissues were found to be toxic in vivo and in vitro. Non-oxidative metabolism of ethanol resulting in the formation of fatty acid ethyl esters (FAEEs) appears to be one of the major pathways of ethanol disposition in the pancreas during chronic alcohol abuse, and could be associated with pancreatitis. In most cases, pancreatic damage occurs in alcoholics preceding the onset of clinical pancreatitis. Early markers of ethanol-induced pancreatitis could be important for early prevention of such injury. Although FAEEs have been implicated in the ethanol-induced pancreatitis, mechanism(s) of such injury is not well understood. Studies by others and by our own group have shown that plasma levels of FAEEs correlate well with plasma/blood alcohol concentration. FAEE synthase is known to catalyze the formation of FAEEs. The activity of FAEE synthase was found highest in the pancreas. Excessive synthesis of FAEEs during chronic alcohol abuse in the pancreas may be associated with pancreatic injury as supported by in vivo and cell culture studies. Human studies correlating plasma FAEE levels with that of markers of pancreatic injury could be important in developing markers of ethanol-induced toxicity. Although toxicity of exogenously administered FAEEs is shown in vivo and in vitro, the toxicity associated with endogenously formed FAEEs has not been studied. Therefore, studies regarding the role of endogenously formed FAEEs could be important in understanding the mechanism of ethanol-induced pancreatitis.
Kaphalia
B S
BS
Department of Pathology, University of Texas Medical Branch, Galveston 77555, USA. bkaphali@utmb.edu
Ansari
G A
GA
D000437:Alcoholism / Q000150:complications / Q000378:metabolism; D015415:Biomarkers; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology* / Q000378:metabolism*
D015415:Biomarkers; D005227:Fatty Acids; D000431:Ethanol