Non-Oxidative Metabolism of Ethanol by Rat Pancreatic Acini

Abstract

Background: The pathogenesis of alcoholic pancreatitis may involve the metabolism of ethanol (via oxidative and non-oxidative pathways) within the pancreas. The aims of this study were to determine the rate of non-oxidative metabolism in isolated rat pancreatic acini and to compare this to the rate of ethanol oxidation. Methods: Pancreatic acini were isolated from male Sprague-Dawley rats and incubated with ¹⁴C-ethanol. Radiolabelled fatty acid ethyl esters (non-oxidative metabolites) were isolated from lipid extracts by thin-layer chromatography. Radiolabelled acetate (oxidative metabolite) was isolated from the incubation medium by ion-exchange chromatography. Results: Non-oxidative metabolism by isolated pancreatic acini was demonstrated. At 50 and 100 mmol/l ethanol, fatty acid ethyl ester concentrations were 49.6 ± 13.3 and 199 ± 93 µmol/l, respectively. These levels have previously been shown to result in tissue injury. Non-oxidative metabolism was increased 9-fold by addition of oleic acid and inhibited by the lipase inhibitor, tetrahydrolipstatin, by 91.05 ± 1.99%. The rate of oxidative metabolism was 21-fold higher than that of non-oxidative metabolism. Conclusions: Intact pancreatic cells metabolize ethanol by the non-oxidative pathway, generating fatty acid ethyl esters at a rate sufficient to cause pancreatic damage. Oxidative metabolism of ethanol occurs at a much higher rate and may also play a role in pancreatitis.