Non-oxydative ethanol metabolites decrease intracellular ATP level in human pancreatic ductal epithelial cell line

Background: Excessive ethanol consumption is one of the most common causes of acute pancreatitis. Several studies suggest that the toxic effects of alcohol are mediated by its non-oxidative metabolites. Criddle et al. found that fatty acid ethyl esters (FAEE) induce reversible, dose-dependent calcium signalling and inhibit ATP production in isolated pancreatic acinar cells. However, no information is available concerning the effects of ethanol metabolites on pancreatic ductal epithelial cells (PDEC). The aim of this study was to characterize the effects of palmitoleic acid ethyl ester (POAEE) and palmitoleic acid (POA) on intracellular ATP level (ATP)i in PDEC. Methods: In our experiments human pancreatic adenocarcinoma cell line was used (CAPAN1). Different concentrations of ethanol, POAEE and POA were dissolved in standard HEPES solution. Changes in (ATP)i of CAPAN-1 cells were measured using microfluorometry. Results: Administration of low concentration (10–50 mM) of ethanol did not induce (ATP)i depletion; however, 100mM ethanol induced significant, but reversible (ATP)i decrease. The non-oxidative ethanol metabolite POAEE had no significant effect on (ATP)i level in neither of the tested concentrations (50–200µM). The free fatty acid POA, which is supposed to be the most toxic end product of non-oxidative ethanol metabolism, induced dose-dependent, significant and irreversible (ATP)i depletion.

Conclusions: These results suggest that non-oxidative ethanol metabolites induce (ATP)i depletion in pancreatic ductal epithelial cells, which can contribute to the development of acute pancreatitis. The effect of ethanol metabolites on ductal bicarbonate secretion needs further investigation.

This work was supported by OTKA, Hungarian Academy of Sciences and National Development Agency.