姜黃和乙醇對(duì)染苯小鼠CYP2E1及血液學(xué)毒性的影響的綜述報(bào)告VIP

姜黃和乙醇對(duì)染苯小鼠CYP2E1及血液學(xué)毒性的影響的綜述報(bào)告摘要本文綜述了姜黃和乙醇對(duì)染苯小鼠CYP2E1及血液學(xué)毒性的影響。結(jié)果表明，姜黃和乙醇均可顯著增加染苯小鼠肝臟中CYP2E1表達(dá)水平，且在聯(lián)合作用下更為顯著。同時(shí)，姜黃和乙醇對(duì)染苯小鼠造成了不同程度的血液學(xué)毒性影響，包括白細(xì)胞計(jì)數(shù)、紅細(xì)胞計(jì)數(shù)、血紅蛋白含量、血小板計(jì)數(shù)等。然而，姜黃和乙醇在一定程度上可以減輕染苯引起的某些血液學(xué)毒性表現(xiàn)，這可能與它們的抗氧化和抗發(fā)炎作用有關(guān)。因此，在染苯中毒治療中可能具有一定的應(yīng)用前景。關(guān)鍵詞：姜黃、乙醇、染苯、CYP2E1、血液學(xué)毒性IntroductionBenzene(C6H6)isawell-knowntoxicenvironmentalpollutantthatiswidelyusedinindustryanddailylife.Chronicexposuretobenzenecancauseaseriesofhematologicaltoxicities,includingaplasticanemia,pancytopenia,andmyelodysplasticsyndrome,whichhasbecomeaglobalhealthconcern(1).CYP2E1,amajorcytochromeP450enzymeinvolvedinthemetabolismofbenzene,isresponsibleforthegenerationoftoxicbenzenemetabolitessuchas1,2-dihydroxybenzeneand1,4-benzoquinone(2).OverexpressionofCYP2E1canexacerbatebenzene-inducedhematotoxicitybyincreasingtheproductionoftoxicmetabolites,whileinhibitionofCYP2E1activitycanreducebenzenetoxicity(3).Curcumin,themainactiveingredientinturmeric,hasbeenwidelyinvestigatedforitsanti-inflammatory,antioxidant,andanti-canceractivities(4).Studiesindicatethatcurcumincanprotectagainstbenzene-inducedtoxicitybyinhibitingCYP2E1-mediatedbenzenemetabolismandscavengingfreeradicals(5).Ethanol,anothercommonlyconsumedsubstance,hasbeenreportedtoaffectbenzenemetabolismandtoxicity(6).However,theeffectsofcurcuminandethanolonCYP2E1activityandhematologicaltoxicityinbenzene-exposedanimalsremaincontroversial.Therefore,thisreviewaimstosummarizetheeffectsofcurcuminandethanolonCYP2E1expressionandhematologicaltoxicityinbenzene-exposedmice.EffectsofcurcuminonCYP2E1expressionStudieshavedemonstratedthatcurcumincaninhibitCYP2E1expressionandactivityinvarioustissues,includingliver,kidney,andlung(7).Inabenzene-exposedmousemodel,curcuminsignificantlyreducedthelevelsofCYP2E1mRNAandproteinintheliver,aswellasthelevelsof1,2-dihydroxybenzeneand1,4-benzoquinoneintheblood(8).Inaddition,curcumininhibitedbenzene-inducedoxidativestressbyenhancingantioxidantenzymeactivities,suchassuperoxidedismutaseandglutathioneperoxidase(9).Thesefindingssuggestthatcurcumincanprotectagainstbenzene-inducedtoxicitybysuppressingCYP2E1expressionandreducingtheproductionoftoxicmetabolites.EffectsofethanolonCYP2E1expressionEthanolhasbeenreportedtoinduceCYP2E1expressionandactivityintheliver,whichcanexacerbatethetoxicityofvariouschemicals,includingbenzene(10).Inabenzene-exposedmousemodel,ethanolsignificantlyincreasedtheexpressionandactivityofCYP2E1intheliver,aswellasthelevelsof1,2-dihydroxybenzeneand1,4-benzoquinoneintheblood(11).Interestingly,thecombinationofcurcuminandethanolfurtherelevatedCYP2E1expressionandactivity,suggestingapotentialsynergisticeffectonbenzenemetabolism(12).Theseresultshighlighttheimportanceofavoidingethanolconsumptionduringbenzeneexposuretominimizetheriskofhematologicaltoxicity.EffectsofcurcuminandethanolonhematologicaltoxicityBenzene-inducedhematologicaltoxicityhasbeenwidelydocumentedinanimalandhumanstudies.Inthebenzene-exposedmousemodel,benzenesignificantlyreducedthelevelsofredbloodcells,hemoglobin,andplatelets,aswellasthecountsofwhitebloodcells(13).Interestingly,bothcurcuminandethanolalonecanamelioratecertainaspectsofbenzene-inducedhematologicaltoxicity.Forexample,curcuminincreasedthelevelsofredbloodcellsandhemoglobin,whilereducingthecountsofwhitebloodcells(14).Ethanol,ontheotherhand,increasedthecountsofwhitebloodcellsandplatelets,buthadnosignificanteffectonredbloodcellsorhemoglobin(15).Whencurcuminandethanolwereadministeredincombination,theeffectsonhematologicaltoxicitywerecomplexandvarieddependingonthespecificoutcomemeasures.Forexample,thecombinationsignificantlyincreasedthecountsofwhitebloodcellsandplateletscomparedtobenzeneexposurealone,buthadnosignificanteffectonredbloodcellsorhemoglobin(16).Thesefindingssuggestthatthecombinationofcurcuminandethanolmayhavedifferentialeffectsonvariousaspectsofhematologicaltoxicityinbenzene-exposedanimals.ConclusionThisreviewhighlightstheimportanceofCYP2E1inbenzenemetabolismandhematologicaltoxicity,aswellasthepotentialprotectiveeffectsofcurcuminandthedetrimentaleffectsofethanol.CurcumincaninhibitCYP2E1expressionandprotectagainstbenzene-inducedhematotoxicity,whileethanolcaninduceCYP2E1expressionandexacerbatebenzenetoxicity.Thecombinationofcurcuminandethanolmayhavecomplexanddifferentialeffectsonvariousaspectsofhematologicaltoxicity.Overall,thesefindingssuggestthatcurcuminandethanolshouldbecarefullyevaluatedandused