4/3/2017 Selectedaspectsoftheactionofcobaltionsinthehumanbody

CentEurJImmunol.201540(2):236242. PMCID:PMC4637398
Publishedonline2015Aug3.doi:10.5114/ceji.2015.52837

Selectedaspectsoftheactionofcobaltionsinthehumanbody
KatarzynaCzarnek, 1SylwiaTerpiowska, 1andAndrzejK.Siwicki2
1
LaboratoryofEnvironmentalBiology,InstituteofEnvironmentalEngineering,TheJohnPaulIICatholicUniversityofLublin,Lublin,Poland
2
DepartmentofMicrobiologyandClinicalImmunology,UniversityofWarmiaandMazuryinOlsztyn,Olsztyn,Poland
Correspondingauthor.
Correspondence:KatarzynaCzarnek,LaboratoryofEnvironmentalBiology,InstituteofEnvironmentalEngineering,TheJohnPaulII
CatholicUniversityofLublin,Racawickie14,20950Lublin,Poland.email:kczarnek@kul.pl

Received2015Mar12Accepted2015Apr15.

CopyrightCentralEuropeanJournalofImmunology2015

ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercial3.0UnportedLicense,
permittingallnoncommercialuse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

ThisarticlehasbeencitedbyotherarticlesinPMC.

Abstract Goto:

Cobaltiswidespreadinthenaturalenvironmentandcanbeformedasaneffectofanthropogenicactivity.
Thiselementisusedinnumerousindustrialapplicationsandnuclearpowerplants.Cobaltisanessential
traceelementforthehumanbodyandcanoccurinorganicandinorganicforms.Theorganicformisa
necessarycomponentofvitaminB12andplaysaveryimportantroleinformingaminoacidsandsome
proteinsinnervecells,andincreatingneurotransmittersthatareindispensableforcorrectfunctioningof
theorganism.Itsexcessordeficiencywillinfluenceitunfavourably.Saltsofcobalthavebeenappliedin
medicineinthetreatmentofanaemia,aswellasinsportasanattractivealternativetotraditionalblood
doping.Inorganicformsofcobaltpresentinionform,aretoxictothehumanbody,andthelongerthey
arestoredinthebody,themorechangestheycauseincells.Cobaltgetsintothebodyinseveralways:
firstly,withfoodsecondlybytherespiratorysystemthirdly,bytheskinandfinally,asacomponentof
biomaterials.Cobaltanditsalloysarefundamentalcomponentsinorthopaedicimplantsandhavebeen
usedforabout40years.Thecorrosionofmetalisthemainproblemintheconstructionofimplants.
ThesereleasedmetalionsmaycausetypeIVinflammatoryandhypersensitivityreactions,and
alternationsinbonemodellingthatleadtoasepticlooseningandimplantfailure.Theionsofcobalt
releasedfromthesurfaceoftheimplantareabsorbedbypresentmacrophages,whichareinvolvedin
manyoftheprocessesassociatedwithphagocytoseorthopaedicbiomaterialsparticlesandreleasepro
inflammatorymediatorssuchasinterleukin1(IL1),interleukin6(IL6),tumournecrosisfactor(TNF
),andprostaglandin.

Keywords:cobalt,macrophages,typeIVhypersensitivityreactions,biomaterials,implant

Introduction Goto:

Cobaltoccurrenceandapplication
Cobaltwasdiscoveredin1735byGeorgBrandt.Itisoneoftheessentialtraceelementsinthehuman
body[1].Thiselementbelongstotheeighthirongroup.Cobaltcanoccurinvariousdegreesofoxidation
formsfrom+1to+5.Themostpopularare+2and+3otherformsofthemarerare.Ionsformofcobalt,
suchasCo3+,reactwithvariousacidsandcreatesaltshowevertheCo2+formislessreactive[2].

Cobaltisverywidespreadinthenaturalenvironmentandcanbeformedasaneffectofanthropogenic
activity[3].Itispresentinsmallquantitiesincompoundswithsulphurandarsenic.Thiselementisused
innumerousindustrialapplicationslikewelding,diamondtooling,grinding,chemicalcatalyses,and
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nuclearpowerplants[3,4].Innuclearplants,itcanoccurintworadioactiveformsofcobalt,58Coand
60
Co,whichareformedfromcorrosionerosionofalloyscontainingcobaltandothermetals.Thesetwo
formsproducehighenergyphotons,whichcanbeusedinradiotherapytofighttumours[5,6].

Cobaltisusedintheproductionofalloysinplantsandinceramics,aswellaschemicalcatalyses.
Moreover,compoundsofcobaltareusedinindustrialproductionofpaints,e.g.Thenard'sblue,and
lacquersinglassandceramics[3,4,7].

Organicandinorganiccobalt
Thisessentialelementoccursininorganicandorganicforms.Thefirstformisessentialandnecessaryfor
thehumanbodybutitsexcessordeficiencywillinfluenceitunfavourably.Theorganicformofcobaltis
presentingreenpartsofplants,fish,cereals,andwater[8,9].

Inthehumanbodythiselementispresentinamountsfrom1to2mg:wecanfinditintheheart,liver,
kidney,andspleen,andconsiderablysmallerquantitiesinthepancreas,brain,andserum[10,11].

CobaltisanecessarycomponentofvitaminB12(hydroxocobalamin)andafundamentalcoenzymeof
cellmitosis.Moreover,cobaltisveryimportantforformingaminoacidsandsomeproteinstocreate
myelinsheathinnervecells[3,10].

Cobaltalsoplaysaroleincreatingneurotransmitters,whichareindispensableforcorrectfunctioningof
theorganism[10].Thesaltsofcobaltstimulatethesynthesisoferythropoietin,whichisthemost
importantfunctionintheactivationofdifferentstagesoferythropoiesis,which,inturn,isconnectedwith
theformationoferythrocytesinbonemarrow[12,13].

DeficiencyofcobaltisstronglyrelatedtodisturbancesinvitaminB12synthesis,soitmightcause
anaemiaandhypofunctionofthyroidandincreasetheriskofdevelopmentalabnormalitiesandfailurein
infants[10].

However,excessofthismetalmightincreasetheactionofthyroidandbonemarrow,whichmight,in
turn,leadtooverproductionoferythrocytes,fibrosisinlungs,andasthma[14].

Foralongtimethesaltsofcobalthavebeenappliedinmedicineinthetreatmentofanaemia,aswellasin
sportasanattractivealternativetotraditionalblooddoping.Thismetalenhancessynthesisof
erythropoietin,whichinfluencesenlargementoferythrocytequantityinblood,improvingaerobic
performance,butthemechanismofthisprocessisnotfullyunderstood.However,itisknownthat
hypoxiaisaphysiologicalimpulseinerythropoietinproductionanddecreasestheoxygencontentin
circulatingbloodbybarkofadrenalglandsandliver[12].

Inorganicformsofcobaltpresentinionformaretoxicforthehumanbody.Whenlongerexposed,this
elementisstoredinthebodyandcausesanumberofchangesincells[3,4,9].Cobaltchlorideandcobalt
sulphideareitsinorganicforms,whicharewidelyappliedinthebrewingindustrytheyareaddedto
beertopreventtheformationoffoam.Inpeopleconsuminglargequantitiesofthisdrink,
cardiomyopathy,adisorderofthediastoleoftheleftventricle,hasbeendiagnosed.Significant
accumulationofcobaltintheheartmuscleinthesepeopleisformedpostmortem.Somederivativesof
cobalt,like59Co,areconsideredtobecarcinogenicandarequalifiedassuchbytheInternationalAgency
forCancerResearch[3,5,6].

Cobaltinthehumanbody
Cobaltdailyintakeinadultsis3gwherethecontentofcobaltis0.012g[11].Cobaltgetsintothe
bodyinafewways.Firstly,withfoodsecondlybytherespiratorysystemthirdly,byskinandfinally,as
acomponentofbiomaterials.Biomaterialshavealreadybeeninusefor2000years,buttheirwidespread
usefollowedtheintroductionofpolymethylmetacrylate(PMMA)in1937[15].

Intakeofcobaltwithfood
CobaltgetsintothebodywithfoodasshowninFig.1,andthenitisabsorbedinthesmallintestine.
Thenthemetalgetsintothebloodstreamwhereitisboundtoproteinsandtransportedwithbloodto

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tissuesandcells[12].

Fig.1
Waysofcobaltionsintobody

Therespiratorysystem
Substantialintakeofcobaltcanoccurthroughtherespiratorysystem,especiallyinpeoplewhoare
employedinheavymetalindustryproducingandusingcobaltmetalandcobaltcompounds.Thelungs
absorbaconsiderableamountofcobaltoxidefromdust,weldingfumes,metalliccobalt,andothermetals
[12].

Particlesofcobaltandothermetalsgetthroughtotheupperandlowerrespiratorysystemandtheyare
displaceddependingontheirsize.Thelargeparticlesareswallowedandgettothegulletbutthesmaller
onesgetthroughtheendothelialcellsofthelungs.Thissituationcausesmanychangesandariskoflung
cancer[1,16].

Mostepidemiologicalstudieswerecarriedoutinworkersemployedfortenormoreyearsinheavymetal
manufacturingplants.Inthiscaselungcanceroccurs[7].

Otherstudies,notepidemiological,demonstratedaconnectionbetweeninhalationofcobaltandlung
cancer.Moreover,chroniccobaltexposurecancauserhinitis,asthma,respiratoryirritation,and
inflammation.Thenextstudiesonanimalsdemonstratedthatcobaltexposurecaninducemany
respiratorylesionsandalveolarandbronchiolarneoplasms[7].

AnotherresearchprojectdemonstratedthatthetoxicityofCoionsduringthewetgrindingofalloymetals
cancauseagreaterriskofallergicalveolitisthaninpeopleemployedindryareaswithmuchhigherlevels
ofcobaltions.Thesecobaltionsareabletoinducetheproductionofinflammatorycytokinessuchas
interleukin6(IL6),interleukin8(IL8),andtumournecrosisfactor(TNF),byalveolarmacrophages
aswell[4].

Theskin
Theskinislikeanexternalcoatanditissusceptibletoenvironmentalpollution,especiallyinworkers
whoareemployedinheavyindustry.Skinisthebiggestimmunologicalorgan,whichhasavery
importantfunctioninthehumanbody.Itsroleistodefendthebodyagainstpathogensandharmful
environmentalfactorsand,secondly,itassertscommunicationwiththeexternalbiotope[17].

Theskinisverysensitivewhenexposedtochemicalsandotherpollutionthatcanbefoundinthe
environmentandworkplace[18].Environmentalfactors,especiallyheavymetalssuchascobalt,can
induceallergiccontactdermatitisandmaycauseirritantreactionsontheskin.Allergiccontactdermatitis
affectsfrom1to10percentofthetotalpopulation,andmetalssuchascobalt,nickel,andchromiumcan
causecontactallergy,affecting1015%ofwomenandafewpercentofmen[18,19].

Thesediseasescanoccurespeciallyinworkersexposedtomorespecificoccupationalconditions,suchas
inindustriespreparinghardmetals,diamondpolishing,andrecoveringcobaltpowders.Cobaltionsfrom
differentmetalobjectsandcobaltpowdersinrepetitivecontactwiththeskincanbereleasedfromthese
objectsandthentheydiffusethroughtheskinandcauseallergyandirritantreaction[18,19,21].

Yetanotherstudyhasdemonstratedresultsofskinabsorptionofcobaltinindustrialworkersandin
laboratoryexperimentswithvolunteers.Theseinvestigationswerecarriedoutinfactorieswithhigh
levelsofpollution.Norelationbetweencobaltambientairanditsurinarysecretionwasfound.Onthe
otherhand,whenstudyingheavymetalindustryworkerswhoseskinsustainedcontactwithmaterials
containingcobalt,highlevelsofthismetalinserumandurineweredetected[18,21].

Thenextexperimentswerecarriedoutinthelaboratoryonfourpeople,whowereaskedtoholdtheir
righthandsfor90minutesinaboxwithfreshlymixedwetpowdercontaining515%cobalt.Thelevelof
cobaltwasincreasedbyanorderofmagnitudeafterexposureandremainedunvariedfor48to60hours.

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Anotherstudyevaluatedaninvitrosystemusinghumanabdominalskinobtainedfromautopsyand
syntheticsweat.Thisresearchprovedthatcobaltpassedthroughskinwithsweat[21].

Cobaltgetstothebodythroughtherespiratorysystemandbygastrointestinalorskinabsorption,and
thenitgetsintotheblood,whereisboundtoerythrocytes.Sometimesbindingofmetalbyerythrocytesat
thenormalmembranepotentialissmallbutthisprocesscouldbeacceleratedbythedepolarisationof
membraneortheadditionofthedivalentionophorecation.Thissituationbringsdisorderto
electrochemicalequilibrium,whichcouldresultinextensionofcobaltionsintracellularilybound[13,22].

Thedigestivesystem
Watersolublecobaltgetsintothebodythroughthegastrointestinalsystem,anditisabsorbedfromthe
smallintestinetotheblood.Moreover,largequantitiesofmetalliccobaltanditsoxideindustandfumes
getintothebodythroughlungsandthentheygettothelymphaticandthevascularsystem.Initially,the
concentrationofcobaltionsishighbutitgraduallydecreases,reachingalowerlevelwithin24hours.It
isconnectedwithstoringcobaltionsintheliverandkidneysandurinaryexcretion.Inanother
experimentretentionofinorganiccobaltinanormaladulthumanafterintravenousinjectionwasstudied.
Theinvestigationshowedthatcobaltwasreducedby40%after24hoursandbyasmuchasto70%after
aweekhowever,afteronemonthitdecreasedtoabout20%andafteroneyeartoabout10%,which
meansthatthisamountofcobaltisretained[12,21].

Cobaltisaccumulatedmainlyinliver,kidneys,pancreas,heart,skeleton,andskeletalmuscles.Moreover,
theaimoftheinvestigationwastoanalysethemechanismofbindingcobalttoredcellsexvivo.The
membraneofthesecellswasdepolarisedandtheresultswereasfollows:theconcentrationofcobaltions
incytosolwasabout1%,whichmeansthatthismetalisboundirreversiblytohaemoglobinduringlife,
anditcirculatesinserumpenetratingalltissuesandorgans[13].

Implants
InAmericaabout500,000peopleandinEurope300,000peoplereceivejointimplantseveryyear.This
problemdoesnotconcernonlyoldpeoplebutalsoyoungerones[23,24].Cobaltanditsalloysare
fundamentalcomponentsinorthopaedicimplantsandhavebeenusedforabout40years.Cobaltand
othermetals,likechromium,molybdenum,andnickel,createalloysthatareusedasamaterialto
constructtotalhiparthroplasty[25,26].

Prosthesescanbemadeonlyfrommetals,andtheyarecalledMoM(metalonmetal),ortheycancontain
metalsandpolyethyleneMoP(metalonpolyethylene),oronlyceramics.Biomaterialsarecharacterised
assubstancesdifferentfromamedicamentorcombinationofsyntheticornaturalsubstances,andthey
aimtoreplacenaturalbodytissues.Theyarealsousedintheconstructionofartificialorgansandinthe
productionofmedicalequipment[27].

Thebiokineticsmodelofcobaltinthehumanbody Goto:

ThemodelofsystemicbiokineticsofcobaltwasdevelopedfortheInternationalCommissionon
RadiologicalProtection(ICRP)becauseofconcernforworkerswhointakeradionuclidesoccurringin
thenuclearindustryandasdiagnostictoolsinnuclearmedicine.Theprimarykineticsmodelwascreated
byLeggettin1992andwasboundwithalkalineearthelements.Thestructureoftheprimarymodelwas
basedontheframeworkforbiokineticsofinorganiccobalt[21].

Thismodelhelpsustounderstandthebiologicalbehaviourofinorganiccobaltinthehumanbody.Itwas
basedonmanystudiescarriedoutearlieronhumansandlaboratoryanimalsthatwereexposedto
radioactiveandalsostablecobaltundercontrolledconditions.Thedifferencesbetweeninorganicand
organiccobaltwereestablished.Bothformswereaccumulatedinahighconcentrationintheliverand
retainedinthebodyforalongtime.Thismodeldescribesthecirculationofcobaltionsbetweenblood
andfoursystemictissues:liver,kidneys,skeleton,andotherorgans.Theproposedmodelofbehaviourof
inorganiccobaltisbasedontheearlierdatabySmithetal.(1972)andLetourneauetal.(1972)after
injecting60CoCl2and58CoCl2.Measurementswerepresentedasafractionaltransferperdayfrom
placeswhereinorganiccobaltwasboundandtransferredtoreceptorcompartments.Thissystemicmodel
providesallrecyclingdataaswellasforphasesoflossasurinaryandfaecalexcretionsomeofthese
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resultswerebasedonthedatafromSmithetal.(1972).Thus,thismodelismainlybasedonthedataby
Smithetal.andissupplementedbythedataobtainedfromlaboratoryanimals[21].

ThebiokineticsmodelofinorganiccobaltwascreatedbyR.W.Leggett(2008)andwasbasedonthe
researchofinitialsystemiccobaltcirculationanditsdislocationincompartmentsofthebody.Among
thesecompartmentswere:liver,kidneys,skeleton,othertissues,andblood.Theaimofthisbiokinetics
modelwastoestablishthelevelofcobaltionscirculatinginbloodafterintravenousinjectionof60Coand
58
Co.Thedistributionofcobaltwasexaminebyautoradiographyinthebodyandwasexpressedin
percentages.Thebloodwasdividedintobloodboundtocobaltions,whichistransferredtoorgans,and
bloodremaininginplasma,asshowninFig.2.Furthermore,6%ofcobaltionsareboundbyblood
remaininginplasma,and94%ofcobaltionsaredividedamongvariouscompartments,includingfaecal
andurinaryexcretion.Suchorgansasliver,kidneys,skeleton,andothersalsorepresentedcirculationof
cobaltionsinblood.Forexample,liverreceived35%ofcobaltionsinblood,andthenitwasremoved
fromthisplacein75%oftheseionsintoplasma.Moreover,therestofthecobaltions(20%)containedin
bilegotothesmallintestine,with5%remainingandrepresentingthelongtermretentionofcobaltions.
Kidneysreceive4.5%ofcobaltionsinbloodand5%oftheseionsremaininthekidneys.Anadditional
30%ofcobaltionsgototheurinarybladderfrombloodthatistransferredtoorgans.Moreover,6%of
ionsgototheskeleton,where3%ofthemaredistributedonthetrabecularbonesurfaceand3%tothe
corticalbonesurface.Inaddition,85%ofcobaltionsareremovedfromtheskeletonintoplasma15%of
theseionsrepresentlongtermretention.Moreover,otherorgansreceived16%ofcobaltionsbindingin
blood[21].

Fig.2
Circulationofcobaltionsbetweenbloodandfoursystemictissues

Applicationofcobaltasbiomaterial
Theuseofbiomaterialsinmedicalpracticeshouldmeetseveralconditions,e.g.toxicity,biological
compatibility,healingoftissues,andmechanicalproperties[28,29].

Thetimeofsafeuseofbiomaterialsdependsonseveralfactors.Themostimportantofthemis
biocompatibility.Itisapropertyofbiologicalmaterial,which,besidesitsbasicfunctioninthebody,does
notcauseworseningofthepatient'scondition,oranyothercomplications.Implantswithofgood
compatibilityshouldnotbetoxicorimmunologicallyactive,sotheyshouldnotinducechronicreactions
oraninflammatorycondition.Inmaterialengineeringwecanenhanceseveralgroupsofmaterials,such
asceramics,polymers,carbon,andmetals.Allofthegroupsaredifferent,andtheyarecharacterisedby
differentproperties[28].

ThemetalgroupcontainssteelCrNiMo,titaniumanditsalloys,cobaltalloys,niobium,andprecious
metals.Thesematerialsarecharacterisedbyvariouspropertiessuchassusceptibilitytostretching,
brittleness,andmechanicalresistance.Duetothesepropertiestheyarecommonlyusedintheproduction
ofvariousimplants,buttheyarenotwithoutdefects[15,29,30].

Biomaterialsalwaystriggerareactionintissues.Thebiomaterialusedintheprosthesisplaysavery
importantroleinthesuccessoftheimplant.Therefore,theuseofanybiomaterialsinthebodyis
determinedbythematerial'sbiofunctionalityandbiocompatibility.Thelatteroftheseisveryimportant
butdifficulttodeterminebecauseofanumberofinteractionsbetweenbodysubstancesandbiomaterials
[26].

Onesuchinteractionisinsufficientcorrosionresistanceinbodyfluid.Thecorrosionofmetalisthemain
probleminconstructingimplants.Severalstudieshavedemonstratedthatcorrosionmechanismscan
causethereleaseofionsofCo,Cr,andMointothesurroundingtissueandsynovialfluid[25,31].
Moreover,thesereleasedmetalionsmaycauseinflammatoryandhypersensitivityreactions,and
alternationsinbonemodellingthatleadstoasepticlooseningandimplantfailure[32,33].

Responseofthehumanbodytoimplantation Goto:

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Thepresenceofanimplant,analienbodyinalivingorganism,detectedbytheimmunologicalsystem,
triggerscertaindefensivemechanisms,asshowninFig.2.

Aftertheimplantationofaprosthesisthefirstdefensivereactionisthecreationofbiofilm.Itmeansthat
thesurfaceoftheimplantiscoveredwithserumalbuminandplateletsandisdefinedasanorganicor
nonorganicdepositonthesurfaceofthematerialandcontainscellularelementsandbacteriaandfungi
[15].

Thebacterialformshavetheabilitytobindextracellularmatrixalbuminslikecollagenandfibrinogen,
andcausetheiradhesion(suchas:Staphylococcusaureus,Staphylococcusepidermidis,Escherichiacoli,
Pseudomonasspecies,Enteroccocus).Ifthecolonisationofbacteriaisstoppedbythehost'scells,suchas
macrophagesandfibroblasts,wecannotobserveanychangesinthebody,butsometimesthedefensive
mechanismcanbeweakerthanthepaceofadhesion,andwecanobservethegrowthofanincreasing
numberofbacteria,asshowninFig.3.Thefinalresultofthetissueresponseisthecreationofacollagen
andelastincapsulearoundtheprosthesis.Thissituationcouldleadtovasa'satrophyandnecrosis,bone
resorption,andultimatelyfailureoftheimplant[15,25].

Fig.3
Influenceofcobaltionsreleasedfromsurfaceofimplantand
immunologicalresponsesofbody

Moreover,thissituationcouldbedirectlyconnectedwithworkofimplant.Asmentionedearlier,the
prosthesiscontainsvariousalloysofmetalssuchas:cobalt,copper,chromium,molybdenum,andnickel,
andtheyallreleaseionsintothehosttissuesbecauseofcorrosion.Thebiologicalliquidsinthebody
consistofmanyionsofchlorine,sodium,potassium,lime,phosphates,andorganiccomponents,andin
additionahighertemperatureofthebodyandchangesofpHintissuessurroundingtheimplantcausethe
processofcorrosionofmetals[28,29].Theseionsarereleasedovertime,andtheirlevelcanbehighly
significantbecausetheyarethesourceofmanypathophysiologicaleffects.Studieshavedemonstrateda
sevenfoldincreaseinmetalionsinthesynovialfluid.AnotherinvestigationhasshownthatCrandCo
ionsincreasethereleaseofproinflammatorycytokinesfrommacrophagesandinhibitionofosteoblasts,
osteoclasts,andTandBcellproliferation[32].Moreover,weardebriscouldbeaccumulatedatthe
highestdosesintheadjacenttissuesandbonemarrowandcouldcirculateinthebloodstreamand
penetrateotherorgansinthebody[24,34].

Theimplantisanalien,foreignbody,andtheorganismwillactivatesomemechanismswhichaimatits
destruction.Macrophagesarethetypeofleukocytesthat,afterreachingmaturity,leavethetissueandget
intothebloodstream.Thesecellsareveryimportantcomponentsoftheimmunologicalsystemandthey
synthesisecytokinesandotherfactorsthatinitiateinflammationandboneresorption.Allofthemcause
osteolysisandasepticlooseningandfailureofprostheses[26,36].

Thereleasedionsofmetalsfrommetalonthemetalsurfaceofperiprostheticscouldenterthebloodstream
andcirculateonthebodyandultimatelyaccumulateintheheart,liver,kidney,spleen,pancreas,and
lymphatictissue,andonlyapartofthemwillbeeliminatedthroughurine.Thismetallicdebrismayhave
directtoxicologicaleffectsoveralongtime[37].

Themetalliccorrosionproductscanpenetratethecellplasmamembrane,bindcellularproteinsor
enzymes,andmodulatecytokineexpression.Osteolysis,andasepticandnonasepticlooseningaremajor
causesofimplantfailure[26,38,39].

ThereactionofthebodytoionsofcobaltandothermetalsisatypeIVhypersensitivityreaction.The
ionsofcobaltandothermetalsreleasedfromthesurfaceoftheimplantareabsorbedbypresent
macrophages,whichareinvolvedinmanyoftheprocessesassociatedwithphagocytoseorthopaedic
biomaterialparticles.Iftheseionscannotbedestroyedafterphagocytosisofmacrophagesthenthe
macrophagesresolveandreleaseproinflammatorymediatorssuchasIL1,IL6,TNF,and
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prostaglandin,asshowninFig.4.TheproinflammatorycytokinessuchasIL1andstimulate
resorptionofbone,andthentheyactsynergisticallytothetumournecrosisfactorTNF.Moreover,
macrophagesreleasematrixmetalloproteinases(MMPs)andchemokines[3942].

Fig.4
Responsesofmacrophagesonactivityofcobaltionsreleasedfrom
implantsurface

ThedelayedtypeIVhypersensitivityreactionisatypeofimmuneresponsewhereThhelperand
cytotoxicTccellsarealsoengaged.Thcellsareresponsibleforthedamageofinfectedtissuesby
macrophagesandtheactivationofcytokines.AnothertypeofcytotoxicTcprovidescellmediates,which
areresponsibleforcytolysis[26].

Summary Goto:

Cobaltisanessentialtraceelementforthehumanbody.Thismetalisverywidespreadinthenatural
environmentandcanbeformedasaneffectofanthropogenicactivity.Thismetaloccurrsintwoforms:
organicandinorganic.Theorganicformofcobaltispresentinthegreenpartsofplants,fish,cereals,and
water,anditisanecessarycomponentofvitaminB12.Cobaltgetsintothebodyinafewways:firstly,
withfoodsecondlybytherespiratorysystemthirdly,bytheskinandfinally,asacomponentof
biomaterials.Cobaltanditsalloysarefundamentalcomponentsinorthopaedicimplantsandhavebeenin
useforabout40years.Theuseofbiomaterialsinmedicalpracticeshouldmeetseveralconditions,e.g.
toxicity,biologicalcompatibility,healingoftissues,andmechanicalproperties.Thecorrosionofmetalis
themainproblemintheconstructionofimplants.

Theconditionoftheindividualpatientshouldbeconsideredwhenselectingtheimplant.Moreover,a
patientwithendoprosthesisMoMshouldbemonitored,especiallyregardingtheconcentrationofcobalt
ionsinthesystemicliquid.

Inorganicformsofcobaltaretoxicandcanaccumulateintissuesandevokeachainofchangesincells.
Cobaltionsreleasedfromtheimplantsurfacecancausetoxicandimmunologicalreactions.

Moreover,cobaltionsarereleasedforalongtimeandtheconcentrationofcobaltcandevelopinto
metalosis,andcobaltionscirculatingwithbloodcouldaccumulateinotherorgans,suchas:heart,liver,
spleen,lymphnodes,andkidneys,wheretheionsareexcretedwithurineandexcrement.Also,these
ionscouldinducecytotoxicityandgenotoxicityeffectsinbodycells.Asillustrated,theinfluenceof
cobaltionsonthebodyshouldbestudieddeeply,aswellasinteractionsbetweenionsofcobaltandother
metalsoccurringinbodyfluid.Perhapstheseinteractionshavesomespecificandsignificanteffectson
theimmunologicalsystem.

Theauthorsdeclarenoconflictofinterest.

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