METABOLISM OF ETHANOL BY RAT PANCREATIC ACINAR-CELLS

It has been postulated that ethanol-induced pancreatic injury may be m ediated by the oxidation of ethanol within the pancreas with secondary toxic metabolic changes, but there is little evidence of pancreatic e thanol oxidation. The aims of this study were to determine whether pan creatic acinar cells metabolize significant amounts of ethanol and, if so, to compare their rate of ethanol oxidation to that of hepatocytes . Cultured rat pancreatic acinar cells and hepatocytes were incubated with 5 to 50 mmol/L carbon 14-labeled ethanol (25 dpm/nmol). Ethanol o xidation was calculated from the production of C-14-labeled acetate th at was isolated by Dowex ion-exchange chromatography. Ethanol oxidatio n by pancreatic acinar cells was demonstrable at all ethanol concentra tions tested. At an intoxicating ethanol concentration (50 mmol/L), C- 14-labeled acetate production (227 +/- 20 nmol/10(6) cells/h) approach ed that of hepatocytes (337 +/- 61 nmol/10(6) cells/h). Phenanthroline tan inhibitor of classes I through III isoenzymes of alcohol dehydrog enase (ADH)) inhibited pancreatic ethanol oxidation by 90%, but 4-meth ylpyrazole (a class I and II ADH inhibitor), carbon monoxide (a cytoch rome P450 inhibitor), and sodium azide (a catalase inhibitor) had no e ffect. This study has shown that pancreatic acinar cells oxidize signi ficant amounts of ethanol. At intoxicating concentrations of ethanol, pancreatic acinar cell ethanol oxidation may have the potential to con tribute to pancreatic cellular injury. The mechanism appears to involv e the class III isoenzyme of ADH.