Diclofenac Sodium Inhibits Hepatic Tryptophan 2,3-Dioxygenase but Augments Brain Indoleamine 2,3-Dioxygenase Activities in Rats

Journal of Basic and Applied Sciences

Samina Bano¹  Shazia Dawood¹  Elvis O. Wambiya¹ 

关键词: Dicolfenac sodium;    tryptophan;    kynurenine;    indoleamine 2;    3-dioxygenase;    tryptophan 2;    3-dioxygenase;   

DOI  :  

学科分类：生物科学（综合）

来源: Lifescience Global

【 摘 要 】

Tryptophan2,3-dioxygenase(TDO)existonlyinliverwhileindoleamine2,3-dioxygenase(IDO)existsubiquitouslyinthebody,thesearethemostrate-limitingenzymesofkynureninepathway(KP).Inresponsetoelevatedlevelsofcortisolandpro-inflammatorycytokines,bothenzymesshowincreaseactivityinpatientswithdepressionorAlzheimerdisease(AD).Non-steroidalanti-inflammatorydrugsmayprotectagainstbothdepressionandAD,butobservationalstudieshaveofferedcontradictoryresults.Presentstudyevaluatestheeffectsofanti-inflammatorydiclofenacsodium(DS)onrathepaticTDOandbrainIDOactivities.AdultAlbinoWistarratsweredividedintocontrolandtestgroups,eachtestgroupreceivedDS(2mg/kg)i.p.injectiondailyandwerekilledeitherafter3.5hours(acutetreatment)orafter3,5and7days(chronictreatment)whilecontrolgroupsreceivedanequalvolumeofvehicle.ResultsshowthatTDOenzymeactivitywasinhibitedandlivertryptophanconcentrationswereincreasedafter3to7daystreatmentofDS;howevernoeffectwasseenontheseparametersafter3.5hrs.BrainIDOactivitywasincreasedafterbothacuteandchronicDStreatment.ItisconcludedthatDSinhibitshepaticTDOenzymeactivityfollowingchronictreatment,whileaugmentsbrainIDOactivityfollowingbothacuteandchronicDStreatment,thismayresultinriseincerebralkynurenicacidand/orquinolinicacidconcentrations.ThereforethereisaneedthateffectsofDSonkynureninepathwayshouldbefurtherinvestigatedtoruleouttheprotectiveeffectofDSininflammation-induceddepressionandAlzheimerdisease.

【 授权许可】

Unknown