對(duì)乙酰氨基酚致藥物性肝損傷的機(jī)制研究進(jìn)展

對(duì)乙酰氨基酚致藥物性肝損傷的機(jī)制研究進(jìn)展一、本文概述Overviewofthisarticle對(duì)乙酰氨基酚（Paracetamol，簡(jiǎn)稱PCA），也稱為撲熱息痛，是一種廣泛使用的非處方解熱鎮(zhèn)痛藥，因其良好的療效和較低的不良反應(yīng)發(fā)生率而深受患者歡迎。然而，隨著其使用的普及，對(duì)乙酰氨基酚引起的藥物性肝損傷（Drug-InducedLiverInjury，簡(jiǎn)稱DILI）也逐漸受到關(guān)注。本文旨在綜述對(duì)乙酰氨基酚致藥物性肝損傷的機(jī)制研究進(jìn)展，以期為臨床安全用藥提供參考。Paracetamol(PCA),alsoknownasparacetamol,isawidelyusedover-the-counterantipyreticandanalgesicdrugthatispopularamongpatientsduetoitsgoodtherapeuticeffectandlowincidenceofadversereactions.However,withitswidespreaduse,druginducedliverinjury(DILI)causedbyacetaminophenhasgraduallyreceivedattention.Thisarticleaimstoreviewtheresearchprogressonthemechanismofacetaminopheninduceddrug-inducedliverinjury,inordertoprovidereferenceforsafeclinicalmedication.文章首先回顧了對(duì)乙酰氨基酚的藥理作用及其在臨床上的廣泛應(yīng)用，然后重點(diǎn)分析了對(duì)乙酰氨基酚引起肝損傷的主要機(jī)制，包括其代謝過程中產(chǎn)生的活性代謝產(chǎn)物對(duì)肝細(xì)胞的直接毒性作用，以及氧化應(yīng)激、線粒體功能障礙、凋亡和壞死等細(xì)胞死亡途徑的激活。文章還將探討個(gè)體差異、遺傳因素、藥物相互作用以及長(zhǎng)期大量使用等因素如何影響對(duì)乙酰氨基酚的肝毒性。Thearticlefirstreviewsthepharmacologicaleffectsandwidespreadclinicalapplicationsofacetaminophen,andthenfocusesonanalyzingthemainmechanismsofacetaminopheninducedliverinjury,includingthedirecttoxiceffectsofactivemetabolitesproducedduringitsmetabolismonlivercells,aswellastheactivationofcelldeathpathwayssuchasoxidativestress,mitochondrialdysfunction,apoptosis,andnecrosis.Thearticlewillalsoexplorehowindividualdifferences,geneticfactors,druginteractions,andlong-termheavyusecanaffectthehepatotoxicityofacetaminophen.在綜述當(dāng)前研究進(jìn)展的基礎(chǔ)上，本文還將展望未來的研究方向，以期進(jìn)一步揭示對(duì)乙酰氨基酚致藥物性肝損傷的確切機(jī)制，為預(yù)防和治療對(duì)乙酰氨基酚引起的肝損傷提供新的思路和方法。Onthebasisofreviewingcurrentresearchprogress,thisarticlewillalsolookforwardtofutureresearchdirections,inordertofurtherrevealtheexactmechanismofacetaminopheninduceddrug-inducedliverinjury,andprovidenewideasandmethodsforthepreventionandtreatmentofacetaminopheninducedliverinjury.二、對(duì)乙酰氨基酚的藥理作用與代謝途徑Pharmacologicaleffectsandmetabolicpathwaysofacetaminophen對(duì)乙酰氨基酚（Paracetamol，簡(jiǎn)稱PCA）是一種廣泛使用的非處方藥物，主要用于緩解輕度至中度的疼痛以及退燒。其在體內(nèi)的藥理作用主要是通過抑制中樞神經(jīng)系統(tǒng)中的前列腺素合成來實(shí)現(xiàn)鎮(zhèn)痛和解熱作用。對(duì)乙酰氨基酚還具有一定的抗炎和抗風(fēng)濕作用。Paracetamol(PCA)isawidelyusedover-the-countermedicationprimarilyusedtoalleviatemildtomoderatepainandreducefever.Itspharmacologicaleffectsinthebodyaremainlyachievedbyinhibitingthesynthesisofprostaglandinsinthecentralnervoussystemtoachieveanalgesicandantipyreticeffects.Acetaminophenalsohascertainanti-inflammatoryandantirheumaticeffects.對(duì)乙酰氨基酚在體內(nèi)的代謝途徑主要經(jīng)過肝臟進(jìn)行。在肝臟中，對(duì)乙酰氨基酚首先被細(xì)胞色素P450（CYP）酶系，特別是CYP2E1和CYP3A4催化，生成一種稱為N-乙酰對(duì)苯醌亞胺（NAPQI）的中間代謝產(chǎn)物。NAPQI在正常情況下會(huì)被肝臟中的谷胱甘肽（GSH）迅速清除，從而避免對(duì)肝臟細(xì)胞的毒性作用。然而，當(dāng)對(duì)乙酰氨基酚攝入過量，或者肝臟中GSH儲(chǔ)備不足時(shí)，NAPQI會(huì)積累并與肝臟細(xì)胞內(nèi)的蛋白質(zhì)結(jié)合，導(dǎo)致蛋白質(zhì)功能喪失和肝臟細(xì)胞的損傷。Themetabolicpathwayofacetaminopheninthebodymainlypassesthroughtheliver.Intheliver,acetaminophenisfirstcatalyzedbythecytochromeP450(CYP)enzymesystem,particularlyCYP2E1andCYP3A4,toproduceanintermediatemetabolitecalledN-acetylhydroquinoneimine(NAPQI).NAPQIisrapidlyclearedbyglutathione(GSH)intheliverundernormalcircumstances,therebyavoidingtoxiceffectsonlivercells.However,whenexcessiveintakeofacetaminophenorinsufficientGSHreservesintheliveroccur,NAPQIaccumulatesandbindstoproteinswithinlivercells,leadingtolossofproteinfunctionanddamagetolivercells.對(duì)乙酰氨基酚還可以通過其他途徑產(chǎn)生毒性。例如，當(dāng)對(duì)乙酰氨基酚與乙醇同時(shí)使用時(shí)，乙醇可以通過抑制肝臟中GSH的合成，增加NAPQI的積累，從而加劇對(duì)乙酰氨基酚的肝毒性。因此，了解對(duì)乙酰氨基酚的藥理作用和代謝途徑，對(duì)于預(yù)防和治療其引起的藥物性肝損傷具有重要的指導(dǎo)意義。Acetaminophencanalsoproducetoxicitythroughotherpathways.Forexample,whenacetaminophenisusedtogetherwithethanol,ethanolcanexacerbatethehepatotoxicityofacetaminophenbyinhibitingthesynthesisofGSHintheliver,increasingtheaccumulationofNAPQI.Therefore,understandingthepharmacologicaleffectsandmetabolicpathwaysofacetaminophenisofgreatguidingsignificanceforthepreventionandtreatmentofdrug-inducedliverinjurycausedbyit.近年來，隨著對(duì)藥物性肝損傷機(jī)制的深入研究，人們發(fā)現(xiàn)了一些新的與對(duì)乙酰氨基酚肝毒性相關(guān)的因素，如氧化應(yīng)激、線粒體功能障礙、自噬和凋亡等。這些新的發(fā)現(xiàn)為我們提供了更深入的理解對(duì)乙酰氨基酚肝毒性的機(jī)制，也為尋找新的預(yù)防和治療策略提供了思路。Inrecentyears,withthein-depthstudyofthemechanismofdrug-inducedliverinjury,somenewfactorsrelatedtoacetaminophenhepatotoxicityhavebeendiscovered,suchasoxidativestress,mitochondrialdysfunction,autophagy,andapoptosis.Thesenewfindingsprovideuswithadeeperunderstandingofthemechanismofacetaminophenhepatotoxicity,aswellasideasforfindingnewpreventionandtreatmentstrategies.三、對(duì)乙酰氨基酚致藥物性肝損傷的機(jī)制Themechanismofacetaminopheninduceddrug-inducedliverinjury對(duì)乙酰氨基酚（Paracetamol,APAP）是一種常見的解熱鎮(zhèn)痛藥，廣泛用于各種疼痛和發(fā)熱癥狀的緩解。然而，其過量使用或長(zhǎng)期大量使用可能引發(fā)藥物性肝損傷（Drug-InducedLiverInjury,DILI），這已成為一個(gè)不容忽視的公共衛(wèi)生問題。近年來，關(guān)于對(duì)乙酰氨基酚致藥物性肝損傷的機(jī)制研究取得了顯著進(jìn)展，為預(yù)防和治療這一疾病提供了新的思路。Paracetamol(APAP)isacommonantipyreticandanalgesicdrugwidelyusedforthereliefofvariouspainandfeversymptoms.However,excessiveorprolongeduseofitmayleadtodrug-inducedliverinjury(DILI),whichhasbecomeasignificantpublichealthissuethatcannotbeignored.Inrecentyears,significantprogresshasbeenmadeinthestudyofthemechanismofacetaminopheninduceddrug-inducedliverinjury,providingnewideasforthepreventionandtreatmentofthisdisease.對(duì)乙酰氨基酚在肝臟中主要通過葡萄糖醛酸化和硫酸化兩種途徑進(jìn)行代謝。正常劑量下，這些代謝途徑可以有效地將對(duì)乙酰氨基酚轉(zhuǎn)化為無毒或低毒性的代謝產(chǎn)物。然而，當(dāng)對(duì)乙酰氨基酚攝入過量時(shí)，其代謝過程中產(chǎn)生的活性中間產(chǎn)物N-乙酰基-對(duì)-苯醌亞胺（NAPQI）會(huì)大量積累，對(duì)肝臟細(xì)胞產(chǎn)生直接毒性作用。Acetaminophenismainlymetabolizedintheliverthroughtwopathways:glucuronidationandsulfation.Atnormaldoses,thesemetabolicpathwayscaneffectivelyconvertacetaminophenintonon-toxicorlowtoxicmetabolites.However,whenexcessiveintakeofacetaminophenoccurs,theactiveintermediateN-acetyl-p-benzoquinoimine(NAPQI)producedduringitsmetabolismaccumulatesinlargeamounts,causingdirecttoxiceffectsonlivercells.NAPQI能夠與肝細(xì)胞內(nèi)的蛋白質(zhì)和硫醇類物質(zhì)發(fā)生共價(jià)結(jié)合，導(dǎo)致蛋白質(zhì)功能失活和細(xì)胞內(nèi)氧化還原平衡失調(diào)。NAPQI還能通過氧化應(yīng)激途徑誘導(dǎo)肝細(xì)胞凋亡和壞死。氧化應(yīng)激是指細(xì)胞內(nèi)活性氧（ROS）和活性氮（RNS）的產(chǎn)生與清除失衡，導(dǎo)致細(xì)胞結(jié)構(gòu)和功能受損。對(duì)乙酰氨基酚過量攝入后，NAPQI可刺激線粒體產(chǎn)生大量ROS，進(jìn)而激活多種信號(hào)轉(zhuǎn)導(dǎo)通路，如JNK、p38MAPK和NF-κB等，最終導(dǎo)致肝細(xì)胞損傷。NAPQIcancovalentlybindwithproteinsandthiolsinlivercells,leadingtoproteindysfunctionandimbalanceofintracellularredoxbalance.NAPQIcanalsoinducehepatocyteapoptosisandnecrosisthroughoxidativestresspathways.Oxidativestressreferstoanimbalanceintheproductionandclearanceofreactiveoxygenspecies(ROS)andreactivenitrogenspecies(RNS)withincells,leadingtodamagetocellularstructureandfunction.Afterexcessiveintakeofacetaminophen,NAPQIcanstimulatemitochondriatoproducealargeamountofROS,therebyactivatingvarioussignaltransductionpathways,suchasJNK,p38MAPK,andNF-κBgrade,ultimatelyleadingtolivercelldamage.除了直接毒性作用外，對(duì)乙酰氨基酚還可能通過免疫介導(dǎo)機(jī)制引發(fā)藥物性肝損傷。研究發(fā)現(xiàn)，對(duì)乙酰氨基酚過量攝入后，肝細(xì)胞損傷會(huì)釋放大量損傷相關(guān)分子模式（DAMPs），如高遷移率族蛋白B1（HMGB1）和熱休克蛋白（HSPs）等。這些分子能夠激活肝內(nèi)的免疫細(xì)胞，如巨噬細(xì)胞、自然殺傷細(xì)胞和樹突狀細(xì)胞等，進(jìn)而引發(fā)炎癥反應(yīng)和免疫應(yīng)答。過度的免疫反應(yīng)可能進(jìn)一步加重肝細(xì)胞損傷，形成惡性循環(huán)。Inadditiontoitsdirecttoxiceffects,acetaminophenmayalsocausedrug-inducedliverinjurythroughimmunemediatedmechanisms.Researchhasfoundthatafterexcessiveintakeofacetaminophen,livercelldamagereleasesalargenumberofdamagerelatedmolecularpatterns(DAMPs),suchashighmobilitygroupproteinB1(HMGB1)andheatshockproteins(HSPs).Thesemoleculescanactivateimmunecellsintheliver,suchasmacrophages,naturalkillercells,anddendriticcells,therebytriggeringinflammatoryandimmuneresponses.Excessiveimmuneresponsemayfurtherexacerbatelivercelldamage,formingaviciouscycle.對(duì)乙酰氨基酚致藥物性肝損傷的機(jī)制涉及多個(gè)方面，包括代謝途徑失衡、直接毒性作用、氧化應(yīng)激和免疫介導(dǎo)機(jī)制等。深入研究這些機(jī)制有助于我們更好地理解對(duì)乙酰氨基酚的肝損傷作用，為預(yù)防和治療藥物性肝損傷提供新的策略和方法。Themechanismofacetaminopheninduceddrug-inducedliverinjuryinvolvesmultipleaspects,includingmetabolicpathwayimbalance,directtoxiceffects,oxidativestress,andimmunemediatedmechanisms.Deeplystudyingthesemechanismshelpsusbetterunderstandtheliverinjuryeffectofacetaminophen,providingnewstrategiesandmethodsforthepreventionandtreatmentofdrug-inducedliverinjury.四、對(duì)乙酰氨基酚致藥物性肝損傷的預(yù)防與治療策略Preventionandtreatmentstrategiesfordrug-inducedliverinjurycausedbyacetaminophen對(duì)乙酰氨基酚（APAP）引起的藥物性肝損傷是一個(gè)重要的公共衛(wèi)生問題。了解并掌握其預(yù)防和治療策略對(duì)于減少肝損傷的發(fā)生、提高患者生活質(zhì)量具有重要意義。Druginducedliverinjurycausedbyacetaminophen(APAP)isanimportantpublichealthissue.Understandingandmasteringitspreventionandtreatmentstrategiesisofgreatsignificanceforreducingtheoccurrenceofliverinjuryandimprovingthequalityoflifeofpatients.預(yù)防策略：預(yù)防對(duì)乙酰氨基酚引起的肝損傷關(guān)鍵在于合理使用藥物。患者在使用APAP時(shí)應(yīng)遵循醫(yī)囑，不擅自增加劑量或改變用藥方式。對(duì)于長(zhǎng)期或大量使用APAP的患者，應(yīng)定期進(jìn)行肝功能檢查，以便及時(shí)發(fā)現(xiàn)肝損傷。對(duì)于已經(jīng)存在肝臟疾病或肝功能不全的患者，應(yīng)避免使用APAP或使用時(shí)應(yīng)特別謹(jǐn)慎。Preventionstrategy:Thekeytopreventingliverdamagecausedbyacetaminophenliesintherationaluseofdrugs.PatientsshouldfollowmedicaladvicewhenusingAPAPandnotincreasethedosageorchangethemedicationmethodwithoutauthorization.ForpatientswhouseAPAPforalongtimeorinlargequantities,regularliverfunctiontestsshouldbeconductedtodetectliverdamageinatimelymanner.Forpatientswhoalreadyhaveliverdiseaseorliverdysfunction,APAPshouldbeavoidedorusedwithspecialcaution.治療策略：對(duì)于已經(jīng)發(fā)生對(duì)乙酰氨基酚引起的肝損傷，治療的主要目標(biāo)是減輕肝臟負(fù)擔(dān)，促進(jìn)肝臟修復(fù)。在急性肝損傷階段，應(yīng)立即停用APAP，并給予患者支持性治療，如補(bǔ)充體液、維持電解質(zhì)平衡等?？梢允褂靡恍┚哂斜８巫饔玫乃幬?，如N-乙酰半胱氨酸（NAC）等，以促進(jìn)肝臟修復(fù)。對(duì)于慢性肝損傷，治療策略則更加復(fù)雜，可能需要結(jié)合藥物治療、生活方式調(diào)整等多種手段進(jìn)行綜合治療。Treatmentstrategy:Forliverdamagecausedbyacetaminophen,themaingoaloftreatmentistoreducetheburdenontheliverandpromoteliverrepair.Inthestageofacuteliverinjury,APAPshouldbeimmediatelydiscontinuedandsupportivetreatmentshouldbegiventothepatient,suchassupplementingbodyfluidsandmaintainingelectrolytebalance.Somedrugswithhepatoprotectiveeffects,suchasN-acetylcysteine(NAC),canbeusedtopromoteliverrepair.Forchronicliverinjury,treatmentstrategiesaremorecomplexandmayrequireacombinationofdrugtherapy,lifestyleadjustments,andothercomprehensivetreatments.對(duì)于對(duì)乙酰氨基酚引起的藥物性肝損傷，預(yù)防和治療同樣重要。通過合理使用藥物、定期進(jìn)行肝功能檢查以及采取及時(shí)有效的治療措施，可以最大限度地減少肝損傷的發(fā)生和危害。未來，隨著研究的深入，我們有望發(fā)現(xiàn)更多有效的預(yù)防和治療策略，為應(yīng)對(duì)這一公共衛(wèi)生問題提供更有力的支持。Preventionandtreatmentareequallyimportantfordrug-inducedliverinjurycausedbyacetaminophen.Byusingmedicationreasonably,conductingregularliverfunctiontests,andtakingtimelyandeffectivetreatmentmeasures,theoccurrenceandharmofliverinjurycanbeminimizedtothegreatestextent.Inthefuture,asresearchdeepens,weareexpectedtodiscovermoreeffectivepreventionandtreatmentstrategies,providingstrongersupportforaddressingthispublichealthissue.五、研究展望ResearchOutlook盡管對(duì)乙酰氨基酚引發(fā)的藥物性肝損傷機(jī)制已經(jīng)得到了廣泛的研究，但仍然存在許多未解之謎和需要深入探討的問題。隨著科學(xué)技術(shù)的不斷發(fā)展，未來對(duì)這一領(lǐng)域的研究有望取得更多的突破。Althoughthemechanismofdrug-inducedliverinjurycausedbyacetaminophenhasbeenextensivelystudied,therearestillmanyunsolvedmysteriesandissuesthatneedtobefurtherexplored.Withthecontinuousdevelopmentofscienceandtechnology,futureresearchinthisfieldisexpectedtoachievemorebreakthroughs.從基因?qū)用嫔钊胙芯繉?duì)乙酰氨基酚引發(fā)肝損傷的具體分子機(jī)制，將有助于我們更準(zhǔn)確地預(yù)測(cè)和評(píng)估藥物性肝損傷的風(fēng)險(xiǎn)。通過對(duì)特定基因或基因表達(dá)譜的分析，我們可能能夠找到新的預(yù)防和治療策略。Studyingthespecificmolecularmechanismsofacetaminopheninducedliverinjuryatthegeneticlevelwillhelpusmoreaccuratelypredictandevaluatetheriskofdrug-inducedliverinjury.Byanalyzingspecificgenesorgeneexpressionprofiles,wemaybeabletoidentifynewpreventionandtreatmentstrategies.利用先進(jìn)的生物標(biāo)記物技術(shù)，我們可以更準(zhǔn)確地監(jiān)測(cè)藥物性肝損傷的發(fā)生和發(fā)展。這些生物標(biāo)記物可能包括特定的蛋白質(zhì)、代謝物或microRNA等，它們的變化能夠反映肝臟損傷的程度和類型，從而為我們提供更早、更準(zhǔn)確的診斷依據(jù)。Byutilizingadvancedbiomarkertechnology,wecanmoreaccuratelymonitortheoccurrenceanddevelopmentofdrug-inducedliverinjury.Thesebiomarkersmayincludespecificproteins,metabolites,ormicroRNAs,andtheirchangescanreflectthedegreeandtypeofliverdamage,providinguswithearlierandmoreaccuratediagnosticevidence.隨著人工智能和機(jī)器學(xué)習(xí)等技術(shù)的發(fā)展，我們可以利用這些技術(shù)對(duì)大量的藥物性肝損傷數(shù)據(jù)進(jìn)行深度分析和挖掘，從而發(fā)現(xiàn)新的規(guī)律和趨勢(shì)。這將有助于我們更好地理解藥物性肝損傷的發(fā)病機(jī)制，為未來的藥物研發(fā)和安全性評(píng)價(jià)提供更有力的支持。Withthedevelopmentoftechnologiessuchasartificialintelligenceandmachinelearning,wecanusethesetechnologiestodeeplyanalyzeandminealargeamountofdrug-inducedliverinjurydata,therebydiscoveringnewpatternsandtrends.Thiswillhelpusbetterunderstandthepathogenesisofdrug-inducedliverinjuryandprovidestrongersupportforfuturedrugdevelopmentandsafetyevaluation.我們還需要關(guān)注藥物性肝損傷的預(yù)防和治療策略的研究。通過開發(fā)新的藥物或治療方法，我們可能能夠更有效地預(yù)防和治療藥物性肝損傷，從而保護(hù)患者的肝臟健康。Wealsoneedtofocusontheresearchofpreventionandtreatmentstrategiesfordrug-inducedliverinjury.Bydevelopingnewdrugsortreatmentmethods,wemaybeabletomoreeffectivelypreventandtreatdrug-inducedliverinjury,therebyprotectingtheliverhealthofpatients.對(duì)乙酰氨基酚引發(fā)的藥物性肝損傷機(jī)制仍然是一個(gè)值得深入研究的領(lǐng)域。隨著科學(xué)技術(shù)的不斷發(fā)展，我們有望在未來取得更多的突破和進(jìn)展。Themechanismofdrug-inducedliverinjuryinducedbyacetaminophenremainsafieldworthyofin-depthresearch.Withthecontinuousdevelopmentofscienceandtechnology,weareexpectedtomakemorebreakthroughsandprogressinthefuture.六、結(jié)論Conclusion對(duì)乙酰氨基酚（APAP）作為一種廣泛使用的解熱鎮(zhèn)痛藥，其藥物性肝損傷（DILI）的問題一直備受關(guān)注。近年來，隨著研究的深入，我們對(duì)APAP致藥物性肝損傷的機(jī)制有了更深入的理解。本文從多個(gè)角度對(duì)APAP的肝損傷機(jī)制進(jìn)行了詳細(xì)的探討，包括其代謝過程、活性中間體的形成、以及這些中間體如何與細(xì)胞內(nèi)的蛋白質(zhì)、DNA等生物大分子相互作用，導(dǎo)致肝細(xì)胞損傷和凋亡。Asawidelyusedantipyreticandanalgesicdrug,acetaminophen(APAP)hasalwaysbeenaconcernforitsdrug-inducedliverinjury(DILI).Inrecentyears,withthedeepeningofresearch,wehavegainedadeeperunderstandingofthemechanismofAPAPinduceddrug-inducedliverinjury.ThisarticleprovidesadetailedexplorationoftheliverinjurymechanismofAPAPfrommultipleperspectives,includingitsmetabolicprocess,formationofactiveintermediates,andhowtheseintermediatesinteractwithintracellularproteins,DNA,andotherbiomolecules,leadingtolivercelldamageandapoptosis.研究發(fā)現(xiàn)，APAP的肝毒性主要與其在肝臟中的代謝過程有關(guān)。在正常情況下，APAP主要通過葡萄糖醛酸化和硫酸化兩種途徑代謝。然而，當(dāng)攝入過量時(shí)，APAP的代謝會(huì)轉(zhuǎn)向一條產(chǎn)生高毒性中間體的途徑，即N-乙酰對(duì)苯醌亞胺（NAPQI）。NAPQI能與細(xì)胞內(nèi)的蛋白質(zhì)、DNA等生物大分子結(jié)合，導(dǎo)致細(xì)胞結(jié)構(gòu)和功能的破壞。ResearchhasfoundthatthehepatotoxicityofAPAPismainlyrelatedtoitsmetabolicprocessesintheliver.Undernormalcircumstances,APAPismainlymetabolizedthroughtwopathways:glucuronidationandsulfation.However,wheningestedexcessively,themetabolismofAPAPshiftstowardsapathwaythatproduceshighlytoxicintermediates,namelyN-acetylquinoneimine(NAPQI).NAPQIcanbindtobiologicalmacromoleculessuchasproteinsandDNAwithincells,leadingtothedestructionofcellstruc