Titanium Dioxide Nanoparticles Trigger Loss of Hepatic Function and Perturbation of Mitochondrial Dy

文档简介Titaniumdioxide(TiO2)nanoparticlesareoneofthemosthighlymanufacturednanomaterialsintheworldwithapplicationsincopiousindustrialandconsumerproducts.Theliverisamajoraccumulationsiteformanynanoparticles,includingTiO2,directlythroughintentiona领estionorindirectlythroughincreasedenvironmentalcontaminationandunintentiona领estionviawater,foodoranimals.GrowingconcernsoverthecurrentusageofTiO2coupledwiththelackofmechanisticunderstandingofitspotentialhealthriskisthemotivationforthisstudy.HerewedeterminedthetoxiceffectofthreedifferentTiO2nanoparticles(commerciallyavailablerutile,anataseandP25)onprimaryrathepatocytes.Specifically,weevaluatedeventsrelatedtohepaticfunctionsandmitochondrialdynamics:(1)ureaandalbuminsynthesisusingcolorimetricandELISAassays,respectively;(2)redoxsigna领mechanismsbymeasuringROSproduction;(3)OPA1andMfn-1expressionthatmediatesthemitochondriadynamicsbyPCR;and(4)mitochondrialmorphologybyMitoTrackerGreenFMstaining.AllthreeTiO2nanoparticlesinducedasignificantlossinhepaticfunctionsevenatconcentrationsaslowas20μg/mlwithcommerciallyusedP25causingmaximumdamage.TiO2nanoparticlesinducedastrongoxidativestressinprimaryhepatocytes.TiO2nanoparticlesexposurealsoresultedinmorphologicalchangesinmitochondriaandsignificantlossinthefusionprocess,thusimpairingthemitochondrialdynamics.AlthoughthisstudydemonstratedthatTiO2nanoparticlesexposureresultedinsignificantdamageinprimaryhepatocytes,moreinvitroandinvivostudiesarerequiredtodeterminethecompletetoxicologicalmechanismonprimaryhepatocytesandsubsequentlyliverfunction.