简介：Oxaliplatin,ananticancerdrugcommonlyusedtotreatcolorectalcancerandothertumors,hasanumberofserioussideeffects,mostnotablyneuropathyandototoxicity.Togaininsightsintoitsototoxicprofile,oxaliplatinwasappliedtoratcochlearorgancultures.Consistentwithitneurotoxicpropensity,oxaliplatinselectivelydamagednervefibersataverylowdose1μM.Incontrast,thedoserequiredtodamagehaircellsandspiralganglionneuronswas50foldhigher(50μM).Oxailiplatin-inducedcochlearlesionsinitial-lyincreasedwithdose,butunexpectedlydecreasedatveryhighdoses.Thisnon-lineardoseresponsecouldberelatedtodepressedoxaliplatinuptakeviaactivetransportmechanisms.Previousstudieshavedemon-stratedthataxonaldegenerationinvolvesbiologicallyactiveprocesseswhichcanbegreatlyattenuatedbynicotinamideadeninedinucleotide(NAD+).TodetermineifNAD+wouldprotectspiralganglionaxonsandthehaircellsfromoxaliplatindamage,cochlearculturesweretreatedwithoxaliplatinaloneatdosesof10μMor50μMrespectivelyascontrolsorcombinedwith20mMNAD+.Treatmentwith10μMoxaliplatinfor48hoursresultedinminordamagetoauditorynervefibers,butsparedcochlearhaircells.However,whencochlearculturesweretreatedwith10μMoxaliplatinplus20mMNAD+,mostauditorynervefiberswereintact.50μMoxaliplatindestroyedmostofspiralganglionneuronsandcochlearhaircellswithapop-toticcharacteristicsofcellfragmentations.However,50μMoxaliplatinplus20mMNAD+treatmentgreat-lyreducedneuronaldegenerationsandhaircellmissing.TheresultssuggestedthatNAD+providessignifi-cantprotectionagainstoxaliplatin-inducedneurotoxicityandototoxicity,whichmaybeduetoitsactionsofantioxidant,antiapoptosis,andenergysupply.

简介：Themyocardialprotectionaffordedbyischemicpreconditioning(IPC)canalleviateischemia-reperfusioninjuryinnormalratheart.However,thismyocardialprotectionisseldomstudiedinthetype2diabeticratwithmyocardialischemiadisease.Inthisstudy,weaimedtoevaluatetheeffectsofATP-sensitivepotassiumchannels(KATPchannels)onIPCintheisolatedtype2diabeticratheartandtheroleofthesulfonylureagliclazide.MethodsStreptozotocin(STZ)-inducedtype2diabeticmaleWistarratswithorwithoutgliclazide(64mg/kgbodyweight,orally)andage-matchednon-diabeticcontrolratswereusedforallstudies.TheisolatedheartswereperfusedwithLangendorff'ssystemundertheconstantflow,pressureandtemperatureconditionswithKreb's-Henseleitsolution(K-H).After5minutesofbalanceperfusion,theseratswererandomlydividedintosixgroups:non-diabeticcontrolratswithoutIPC(CIR);non-diabeticcontrolratswithIPC(CIP);diabeticratswithoutIPC(DIR);diabeticratswithIPC(DIP);gliclazide-treateddiabeticratswithoutIPC(GIR);andgliclazide-treateddiabeticratswithIPC(GIP).GroupsCIR,DIR,andGIRweresubjectedto30-minglobalischemiaand60-minreperfusionforinductionofischemia/reperfusioninjury.GroupsCIP,DIP,andGIPweregiventhreecyclesof5-minischemiaand5-minreperfusionasIPC,andthenischemia/reperfusioninjuryprogramwasimplemented.Extentofischemia/reperfusioninjurywasmeasuredintermsofthereleaseoflactatedehydrogenase(LDH),creatinekinase(CK),andcreatinkinase-MB(CKMB)incoronaryeffluent.Afterperfusion,Kir6.2andSUR2AmRNAexpressionsinthemyocardialtissuewerecharacterizedbyfluorescentquantitativereal-timePCRmethod,andKir6.2andSUR2Aproteinexpressionswereassessedbyimmunohistochemistry.ResultInnon-diabeticcontrolrats,thereleaseofLDH,CK,andCK-MBincoronaryeffluentmarkedlydecreasedwithIPCcomparedwithNo-IPC(P<0.05),butnotindiabeticrats.However,ingliclazide-treateddiabeticrats,IPC-induceddecreaseintherele