ACUTE ETHANOL ADMINISTRATION INDUCES OXIDATIVE CHANGES IN RAT PANCREATIC TISSUE

Background-There is mounting clinical evidence that ethanol toxicity t o the pancreas is linked with glutathione depletion from oxidative str ess but there is not experimental proof that this occurs. Aims and met hods-The effect of acute ethanol ingestion (4 g/kg) on the pancreatic content of reduced (GSH) and oxidised (GSSG) glutathione, malondialdeh yde (MDA), and carbonyl proteins were therefore studied in the rat. Re sults-Ethanol caused a significant reduction in GSH (p<0.02) and an in crease in GSSG (p<0.005), MDA (p<0.05), and carbonyl proteins (p<0.05) in the rat pancreas. The GSH/GSSG ratios were significantly decreased after ethanol, especially in rats pretreated with diethylmaleate (DEM ), a GSH blocker. Administration of ethanol after DEM further increase d the rate of lipid and protein oxidation. Pretreatment with cyanamide (an inhibitor of aldehyde dehydrogenase) but not with 4-methylpyrazol e (an alcohol dehydrogenase inhibitor) caused higher production of GSS G and MDA. Conclusions-These findings indicate that acute ethanol redu ces the pancreatic content of GSH, which seems to be protective agains t ethanol toxicity, since its depletion is accompanied by increased ox idative damage to cell structures. The further increase of Lipid perox idation and GSSG production in the presence of cyanamide suggests that acetaldehyde might be responsible for the oxidative changes that occu r in pancreatic cells after ethanol administration.