氧氟沙星对大型溞的毒性效应及多组学机制

氧氟沙星对大型溞的毒性效应及多组学机制摘要：氧氟沙星是目前应用较为广泛的氟喹诺酮类抗菌药物之一。本研究旨在探究氧氟沙星对大型溞的毒性效应及多组学机制。研究结果表明，氧氟沙星在不同浓度下均能导致溞体内抗氧化系统受损，使丙二醛、超氧化物歧化酶、谷胱甘肽还原酶、过氧化氢酶、谷胱甘肽过氧化物酶等指标发生显著改变。同时，氧氟沙星还能够影响溞体内钙离子浓度、细胞色素P450活性等生物指标，导致大型溞的生长发育受到一定程度的抑制。运用转录组、代谢组和蛋白组等多组学技术分析氧氟沙星的作用机制，发现氧氟沙星的毒性效应主要与生物合成、代谢物转化及氧化应激等多个通路相关。总之，本研究有助于深入了解氧氟沙星对溞类生物的毒性效应及其作用机制，为环境污染物风险评估提供科学参考。

关键词：氧氟沙星；大型溞；毒性效应；抗氧化系统；转录组；代谢组；蛋白组

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