?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Ascorbic+acid+enhances+the+inhibitory+effect+of+aspirin+on+neuronal+cyclooxygenase-2-mediated+prostaglandin+E2+production.&rft.creator=Candelario-Jalil%2C+Eduardo&rft.creator=Akundi%2C+Ravi+S.&rft.creator=Bhatia%2C+Harsharan+S.&rft.creator=Lieb%2C+Klaus&rft.creator=Appel%2C+Kurt&rft.creator=Munoz%2C+Eduardo&rft.creator=Hull%2C+Michael&rft.creator=Fiebich%2C+Bernd+L.&rft.subject=Neurochemistry&rft.description=Inhibition+of+neuronal+cyclooxygenase-2+(COX-2)+and+hence+prostaglandin+E2+(PGE2)+synthesis+by+non-steroidal+anti-inflammatory+drugs+has+been+suggested+to+protect+neuronal+cells+in+a+variety+of+pathophysiological+situations+including+Alzheimer's+disease+and+ischemic+stroke.+Ascorbic+acid+(vitamin+C)+has+also+been+shown+to+protect+cerebral+tissue+in+a+variety+of+experimental+conditions%2C+which+has+been+attributed+to+its+antioxidant+capacity.+In+the+present+study%2C+we+show+that+ascorbic+acid+dose-dependently+inhibited+interleukin-1beta+(IL-1beta)-mediated+PGE2+synthesis+in+the+human+neuronal+cell+line%2C+SK-N-SH.+Furthermore%2C+in+combination+with+aspirin%2C+ascorbic+acid+augmented+the+inhibitory+effect+of+aspirin+on+PGE2+synthesis.+However%2C+ascorbic+acid+had+no+synergistic+effect+along+with+other+COX+inhibitors+(SC-58125+and+indomethacin).+The+inhibition+of+IL-1beta-mediated+PGE2+synthesis+by+ascorbic+acid+was+not+due+to+the+inhibition+of+the+expression+of+COX-2+or+microsomal+prostaglandin+E+synthase+(mPGES-1).+Rather%2C+ascorbic+acid+dose-dependently+(0.1-100+microM)+produced+a+significant+reduction+in+IL-1beta-mediated+production+of+8-iso-prostaglandin+F2alpha+(8-iso-PGF2alpha)%2C+a+reliable+indicator+of+free+radical+formation%2C+suggesting+that+the+effects+of+ascorbic+acid+on+COX-2-mediated+PGE2+biosynthesis+may+be+the+result+of+the+maintenance+of+the+neuronal+redox+status+since+COX+activity+is+known+to+be+enhanced+by+oxidative+stress.+Our+results+provide+in+vitro+evidence+that+the+neuroprotective+effects+of+ascorbic+acid+may+depend%2C+at+least+in+part%2C+on+its+ability+to+reduce+neuronal+COX-2+activity+and+PGE2+synthesis%2C+owing+to+its+antioxidant+properties.+Further%2C+these+experiments+suggest+that+a+combination+of+aspirin+with+ascorbic+acid+constitutes+a+novel+approach+to+render+COX-2+more+sensitive+to+inhibition+by+aspirin%2C+allowing+an+anti-inflammatory+therapy+with+lower+doses+of+aspirin%2C+thereby+avoiding+the+side+effects+of+the+usually+high+dose+aspirin+treatment.&rft.publisher=Elsevier&rft.contributor=Raine%2C+Cedric&rft.date=2006-05&rft.type=Journal+(Paginated)&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F5641%2F1%2FJ_Neuroimmunol_Candelario-Jalil_et_al_2006.pdf&rft.identifier=++Candelario-Jalil%2C+Eduardo+and+Akundi%2C+Ravi+S.+and+Bhatia%2C+Harsharan+S.+and+Lieb%2C+Klaus+and+Appel%2C+Kurt+and+Munoz%2C+Eduardo+and+Hull%2C+Michael+and+Fiebich%2C+Bernd+L.++(2006)+Ascorbic+acid+enhances+the+inhibitory+effect+of+aspirin+on+neuronal+cyclooxygenase-2-mediated+prostaglandin+E2+production.++%5BJournal+(Paginated)%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F5641%2F