Celecoxib-inducedgastrointestinal,liverandbrainlesionsinrats,counteractionbyBPC157orL-arginine,aggravationbyL-NAME

摘要： AIMTocounteract/revealcelecoxib-inducedtoxicityandNOsysteminvolvement.METHODSCelecoxib(1g/kgb.w.ip)wascombinedwiththerapywithstablegastricpentadecapeptideBPC157(knowntoinhibittheselesions,10μg/kg,10ng/kg,or1ng/kgip)andL-arginine(100mg/kgip),aswellasNOSblockade[N(G)-nitro-L-argininemethylester(L-NAME)](5mg/kgip)givenaloneand/orcombinedimmediatelyaftercelecoxib.Gastrointestinal,liver,andbrainlesionsandliverenzymeserumvaluesinratswereassessedat24hand48hthereafter.RESULTSThishigh-dosecelecoxibadministration,asaresultofNOsystemdysfunction,ledtogastric,liver,andbrainlesionsandincreasedliverenzymeserumvalues.TheL-NAME-inducedaggravationofthelesionswasnotableforgastriclesions,whileinliverandbrainlesionsthebeneficialeffectofL-argininewasblunted.L-argininecounteractedgastric,liverandbrainlesions.ThesefindingssupporttheNOsystemmechanism(s),bothNOsystemagonization(L-arginine)andNOsystemantagonization(L-NAME),thatonthewholearebehindalloftheseCOXphenomena.AnevenmorecompleteantagonizationwasidentifiedwithBPC157(atboth24hand48h).AbeneficialeffectwasevidentonalltheincreasinglynegativeeffectsofcelecoxibandL-NAMEapplicationandinalltheBPC157groups(L-arginine+BPC157;L-NAME+BPC157;L-NAME+L-arginine+BPC157).Thus,thesefindingsdemonstratedthatBPC157mayequallycounteractbothCOX-2inhibition(counteractingthenoxiouseffectsofcelecoxibonalllesions)andadditionalNOSblockade(equallycounteractingthenoxiouseffectsofcelecoxib+L-NAME).CONCLUSIONBPC157andL-argininealleviategastrointestinal,liverandbrainlesions,redressingNSAIDspost-surgeryapplicationandNOsysteminvolvement. ... （共9頁）