Acuteethanol administration induces oxidative changes inratpancreatic tissue

Background-There ismountingclinical evidence thatethanol toxicity tothepancreasislinked withglutathione depletion fromoxidative stress butthereisnot experimental proofthatthis occurs. Aimsandmethods-Theefect ofacute ethanol ingestion (4glkg) onthepancreatic contentofreduced(GSH)andoxidised (GSSG) glutathione, malondialdehyde (MDA),andcarbonyl proteins werethereforestudied intherat. Results-Ethanol causeda significant reduction in GSH (p<0.02)and an increasein GSSG (p<0.005), MDA (p<005), andcarbonyl proteins (p<005) in theratpancreas. The GSHIGSSG ratios weresignificantly decreased after ethanol, especially inratspretreated with diethyhnaleate (DEM),a GSH blocker. Administration ofethanolafterDEM further increased therateoflipid andprotein oxidation. Pretreatmentwith cyanamide(aninhibitor of aldehyde dehydrogenase) butnotwith4-methylpyrazole(an alcoholdehydrogenase inhibitor) causedhigherproduction of GSSGandMDA. Conclusions-These findings indicate that acuteethanol reduces thepancreatic contentofGSH,whichseemstobeprotective against ethanol toxicity, sinceitsdepletionisaccompanied byincreased oxidativedamagetoceli structures. Thefurther increase oflipid peroxidation andGSSG production inthepresence ofcyanamide suggeststhatacetaldehyde mightbe responsible fortheoxidative changes that occurinpancreatic cells afterethanol administration. (Gut 1996; 38:742-746)