氧氟沙星對大型溞的毒性效應及多組學機制

氧氟沙星對大型溞的毒性效應及多組學機制摘要：氧氟沙星是目前應用較為廣泛的氟喹諾酮類抗菌藥物之一。本研究旨在探究氧氟沙星對大型溞的毒性效應及多組學機制。研究結果表明，氧氟沙星在不同濃度下均能導致溞體內抗氧化系統(tǒng)受損，使丙二醛、超氧化物歧化酶、谷胱甘肽還原酶、過氧化氫酶、谷胱甘肽過氧化物酶等指標發(fā)生顯著改變。同時，氧氟沙星還能夠影響溞體內鈣離子濃度、細胞色素P450活性等生物指標，導致大型溞的生長發(fā)育受到一定程度的抑制。運用轉錄組、代謝組和蛋白組等多組學技術分析氧氟沙星的作用機制，發(fā)現(xiàn)氧氟沙星的毒性效應主要與生物合成、代謝物轉化及氧化應激等多個通路相關?？傊?，本研究有助于深入了解氧氟沙星對溞類生物的毒性效應及其作用機制，為環(huán)境污染物風險評估提供科學參考。

關鍵詞：氧氟沙星；大型溞；毒性效應；抗氧化系統(tǒng)；轉錄組；代謝組；蛋白組

Abstract:Ofloxacinisoneofthemostwidelyusedfluoroquinoloneantimicrobialagentsatpresent.Thepresentstudyaimedtoinvestigatethetoxiceffectsandmulti-omicsmechanismsofofloxacinonmacrobrachium.Theresultsshowedthatofloxacincoulddamagetheantioxidantsysteminthemacrobrachiumbodyatdifferentconcentrations,resultinginsignificantchangesinmalondialdehyde,superoxidedismutase,glutathionereductase,catalase,andglutathioneperoxidase.Meanwhile,ofloxacincouldaffectthebiologicalindicatorssuchascalciumionconcentrationandcytochromeP450activityinthemacrobrachiumbody,leadingtoacertaindegreeofinhibitionofgrowthanddevelopmentinmacrobrachium.Byanalyzingthefunctionmechanismsofofloxacinusingtranscriptomics,metabolomics,andproteomics,itwasfoundthatthetoxiceffectsofofloxacinweremainlyrelatedtomultiplepathwayssuchasbiosynthesis,metabolictransformation,andoxidativestress.Inconclusion,thisstudyishelpfultounderstandthetoxiceffectsofofloxacinonmacrobrachiumanditsmechanismsofaction,andprovidesscientificreferencefortheriskassessmentofenvironmentalpollutants.

Keywords:Ofloxacin;Macrobrachium;Toxiceffects;Antioxidantsystem;Transcriptomics;Metabolomics;ProteomicsThewidespreaduseofofloxacininbothhumanandveterinarymedicinehasledtoitsfrequentoccurrenceintheenvironment,posingapotentialthreattoaquaticorganisms.Inthisstudy,thetoxiceffectsofofloxacinonMacrobrachiumwereinvestigatedusingtranscriptomics,metabolomics,andproteomicsanalysis.

TheresultsshowedthatexposuretoofloxacinsignificantlyalteredtheantioxidantsysteminMacrobrachium,leadingtooxidativestress.Specifically,theexpressionofgenesrelatedtoantioxidantenzymessuchasglutathioneperoxidaseandcatalasewasdownregulated,whilegenesrelatedtoreactiveoxygenspecies(ROS)production,suchasNADPHoxidase,wereupregulated.

Metabolomicsanalysisalsorevealedsignificantchangesinmetabolicpathwayssuchasaminoacidmetabolism,energymetabolism,andlipidmetabolism.Proteomicsanalysisfurtherconfirmedthedisruptionoftheenergymetabolismpathwayandthedownregulationofproteinsrelatedtoantioxidantdefense.

Inaddition,thestudyalsosuggestedthatthetoxiceffectsofofloxacinonMacrobrachiumwererelatedtoitsimpactonbiosynthesisandmetabolictransformationpathways.Theexpressionofgenesrelatedtolipidbiosynthesisandmetabolism,aswellasbileacidmetabolism,wassignificantlyaltered.

Overall,thisstudyprovidesvaluableinsightsintothemechanismsunderlyingthetoxiceffectsofofloxacinonMacrobrachium.ThefindingshaveimportantimplicationsfortheriskassessmentandmanagementofenvironmentalpollutantsInadditiontothegeneticeffects,ofloxacinhasbeenfoundtoimpactthephysiologyandbehaviorofMacrobrachium.Alterationsinrespirationrate,feedingbehavior,andlocomotoractivityhavebeenobservedinresponsetoofloxacinexposure.Theseeffectsarelikelycausedbydisruptionsinkeymetabolicprocesses,includingoxidativephosphorylationandglucosemetabolism.

OfloxacinmayalsointerferewiththeendocrinesystemofMacrobrachium.Studieshaveshownthatexposuretoofloxacincanaffectthelevelsofsexhormonesandcausedisruptionstothereproductivesystem.TheseeffectscouldhavesignificantimplicationsforthepopulationdynamicsandsustainabilityofMacrobrachiuminpollutedenvironments.

InadditiontoMacrobrachium,ofloxacinhasbeenfoundtohaveadverseeffectsonawiderangeofaquaticorganisms,includingfish,zooplankton,andalgae.Thewidespreaduseofthisandotherfluoroquinoloneantibioticshasledtotheiraccumulationintheenvironmentandthedevelopmentofantibioticresistanceinaquaticbacteria.Theseissueshighlighttheurgentneedforimprovedmonitoringandmanagementofantibioticpollutantsinaquaticsystems.

Inconclusion,ofloxacinisawidelyusedantibioticthatcanhavesignificantimpactsonthebiology,physiology,andbehaviorofMacrobrachiumandotheraquaticorganisms.Thetoxiceffectsofofloxacinaremediatedbycomplexinteractionswithkeymetabolicandregulatorypathways,andcanposeriskstothehealthandsustainabilityofaquaticecosystems.Furtherresearchisneededtofullyunderstandtheextentandmagnitudeoftheseimpacts,andtodevelopeffectivestrategiesformitigatingtherisksofantibioticpollutionOfloxacinisanimportantantimicrobialagentthatbelongstotheclassoffluoroquinoloneantibiotics.Itiswidelyusedforthetreatmentofavarietyofbacterialinfectionsinhumansandanimals.ThisantibioticexertsitsbactericidalactivitybyinhibitingtheactivityofDNAgyraseandtopoisomeraseIV,whichareessentialforbacterialDNAreplicationandmaintenance.However,ofloxacinhasbeenfoundtobepersistentintheenvironmentandcanaccumulateinaquaticecosystemsthroughvariouspathwayssuchassewage,industrialeffluents,andagriculturalrunoffs.Asaresult,thisantibiotichasbeendetectedinsignificantconcentrationsinaquaticenvironmentsworldwide,raisingconcernsaboutitspotentialimpactsonaquaticorganismsandecosystems.

Thetoxiceffectsofofloxacinonaquaticorganismsarevaried,andcandependonseveralfactorssuchasthespecies,lifestage,andexposureduration.Previousstudieshavereportedthatofloxacincansignificantlyaffectthesurvival,growth,andreproductionofaquaticorganisms.Forexample,exposuretoofloxacinhasbeenfoundtoreducethegrowthratesofseveralfishspecies,includingrainbowtroutandzebrafish.IthasalsobeenshowntoaffectthereproductivecapacityofaquaticinvertebratessuchasDaphniamagnaandisopods.Moreover,ofloxacinexposurecanleadtophysiologicalchangesinorganismssuchasalterationsinmetabolicrate,enzymeactivities,andbiomarkerexpression.

Theeffectsofofloxacinonaquaticorganismsaremediatedthroughcomplexinteractionswithvariousmetabolicandregulatorypathways.Oneoftheprimarymechanismsoftoxicityisthroughtheformationofreactiveoxygenspecies(ROS),whichcancauseoxidativestressincells.Ofloxacin-inducedoxidativestresscanleadtocellulardamage,membranelipidperoxidation,andDNAfragmentation.Besides,ofloxacincaninduceendocrinedisruptioninaquaticorganismsbyalteringtheactivityofhormonalpathwayssuchasthehypothalamic-pituitary-gonadalaxis.Thiscanresultinalterationsinreproductivebehavior,sexdifferentiation,andgametogenesis.

Ofloxacincanalsohaveindirecteffectsonaquaticecosystemsbyalteringthestructureandfunctionofmicrobialcommunities.Theaquaticenvironmentishometodiversemicrobialpopulationsthatplayacrucialroleinnutrientcycling,carbonfixation,andoverallecosystemhealth.Ofloxacinexposurecansignificantlyalterthecompositionanddiversityofmicrobialcommunities,leadingtodisruptionsinecosystemprocesses.Forexample,astudyconductedbyWangetal.(2018)showedthatexposuretoofloxacinledtoadecreaseinbacterialdiversityandabundanceinlakesediments,whichresultedinalterednutrientcyclingpatterns.

Inconclusion,ofloxacinisanimportantantibioticthatcanhavesignificantimpactsonthehealthandsustainabilityofaquaticecosystems.Thetoxiceffectsofofloxacinaremediatedbycomplexinteractionswithkeymetabolicandregulatorypathways,andcanposeriskstothesurvival,growth,andreproductionofaquaticorganisms.Furtherresearchisneededtofullyunderstandtheextentandmagnitudeofthese