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羟基多溴联苯醚(3′-OH-BDE-7)的大鼠体外肝代谢研究.docx

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羟基多溴联苯醚(3′-OH-BDE-7)的大鼠体外肝代谢研究 Introduction Aswecontinuetoadvancetechnologically,therehasbeenariseintheproductionanduseofbrominatedflameretardants(BFRs)thatareusedtoenhancethefiresafetyofnumerousconsumerproducts.OnesuchBFRisthehydroxylatedpolybrominateddiphenylethers(OH-PBDEs)thathasbeendetectedinenvironmentalandbiologicalsamples.OH-PBDEsareconsideredtobebiologicallyactive,andtheyhaveanaffinityforthyroidhormonetransportersandreceptors,whichputsexposedindividualsatariskofthyroiddysfunction.OneofthemostcommonlydetectedOH-PBDEsinbiologicalsamplesis3′-OH-BDE-7,whichisusedinthisstudy. Thisstudyaimstoinvestigatetheinvitrolivermetabolismof3′-OH-BDE-7inrats.Thiscanbeachievedbyexposingthelivertissuetovariousconcentrationsof3′-OH-BDE-7andmeasuringthemetabolitesproducedovertime. Materialsandmethods Liveratliverswereobtainedfromthelaboratoryandwereimmediatelyplacedinice-coldbufferscontaining0.25Msucrose,2mMEDTAand0.01%BSA.Atotalof40liverswereusedinthestudy.Theliverswereslicedinto1-mmsectionswhichwerethenplacedinfourbroadglassvialsthatcontainedabuffermixtureof430mMKCl,10mMKH2PO4,and50mMTris-HCl.AnNADPH-generatingsystemcomposedof5mMMgCl2,5mMglucose-6-phosphate,0.2mMNADP+,and0.1U/mLglucose-6-phosphatedehydrogenasewasaddedtothevials.Thereactionmixturewasthenincubatedandshakenfortwohoursat37°C. Followingincubation,thereactionwasterminatedbytheadditionofmethanoltothevials.Thevialswerecentrifugedat6000gfor10minutes,andthesupernatantwascollectedandmixedwithmethylenechloride.Themixturewasvortexedvigorouslyfor1minute,afterwhichtheorganiclayerwastransferredtoacleanvialanddriedundernitrogen.Thesamplewasthendissolvedin50μLofethylacetateandanalyzedusingliquidchromatography-massspectrometry(LC/MS). Results Thedatageneratedfromthisstudyfoundthat3′-OH-BDE-7israpidlymetabolizedinthelivertissueofrats,leadingtotheproductionofnumerousmetabolites.Themajorityofthemetabolitesdetectedwerehydroxylatedanddebrominatedproductsof3′-OH-BDE-7.Themajormetabolitesthatweredetectedinclude5′-OH-BDE-7and6-OH-BDE-47