10/15/2016 OchratoxinAWikipedia

OchratoxinA
FromWikipedia,thefreeencyclopedia

OchratoxinAatoxinproducedbyAspergillusochraceus, OchratoxinA
Aspergilluscarbonarius,andPenicilliumverrucosumis
oneofthemostabundantfoodcontaminatingmycotoxins.[1]
Itisalsoafrequentcontaminantofwaterdamagedhouses
andofheatingducts.[2][3]Humanexposurecanoccurthrough
consumptionofcontaminatedfoodproducts,particularly
contaminatedgrainandporkproducts,aswellascoffee,
winegrapes,anddriedgrapes.[4][5][6]Thetoxinhasbeen
foundinthetissuesandorgansofanimals,includinghuman
bloodandbreastmilk.[7]OchratoxinA,likemosttoxic
substances,haslargespeciesandsexspecifictoxicological
differences.[5]

Names
IUPACname
Contents
N{[(3R)5chloro8hydroxy3methyl1oxo3,
1 Impactonhumanandanimalhealth 4dihydro1Hisochromen7yl]carbonyl}L
1.1 Carcinogenicity phenylalanine
1.2 Neurotoxicity Othernames
2 Immunosuppressionandimmunotoxicity (R)N[(5Chloro3,4dihydro8hydroxy3
2.1 Potentiallinktonephropathies
methyl1oxo1H2benzopyran7yl)
2.2 Foodanimalindustryimpact
2.3 Dietaryguidelines carbonyl]Lphenylalanine
3 Dermalexposure ()N[(5Chloro8hydroxy3methyl1oxo
4 Seealso 7isochromanyl)carbonyl]3phenylalanine
5 References Identifiers
CASNumber 303479(http://www.common
chemistry.org/ChemicalDetail.a
Impactonhumanandanimalhealth spx?ref=303479)
ChEBI CHEBI:7719(https://www.ebi.
Carcinogenicity
ac.uk/chebi/searchId.do?chebiId
OchratoxinAispotentiallycarcinogenictohumans(Group =7719)
2B),andhasbeenshowntobeweaklymutagenic,possibly ChEMBL ChEMBL589366(https://www.
byinductionofoxidativeDNAdamage.[8] ebi.ac.uk/chembldb/index.php/c
ompound/inspect/ChEMBL589
Theevidenceinexperimentalanimalsissufficienttoindicate
366)
carcinogenicityofochratoxinA.Itwastestedfor
carcinogenicitybyoraladministrationinmiceandrats.It ChemSpider 390954(http://www.chemspide
slightlyincreasedtheincidenceofhepatocellularcarcinomas r.com/ChemicalStructure.3909
inmiceofeachsex.[9]andproducedrenaladenomasand 54.html)
carcinomasinmalemiceandinrats(carcinomasin46%of ECHAInfoCard 100.005.586(https://echa.europ
malesand5%offemales).[10]Inhumans,verylittlehistology a.eu/substanceinformation//su
dataareavailable,soarelationshipbetweenochratoxinA bstanceinfo/100.005.586)
andrenalcellcarcinomahasnotbeenfound.However,the
IUPHAR/BPS 4672(http://www.guidetophar
incidenceoftransitionalcell(urothelial)urinarycancers
seemsabnormallyhighinBalkanendemicnephropathy macology.org/GRAC/LigandDi

patients,especiallyfortheupperurinarytract.[11]The
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molecularmechanismofochratoxinAcarcinogenicityhas splayForward?tab=summary&li
beenunderdebateduetoconflictingliterature,howeverthis gandId=4672)
mycotoxinhasbeenproposedtoplayamajorrolein Jmol3Dmodel Interactiveimage(http://chema
reducingantioxidantdefenses.[12] pps.stolaf.edu/jmol/jmol.php?m
odel=O%3DC%28O%29%5B
Neurotoxicity C%40%40H%5D%28NC%2
8%3DO%29c1c%28O%29c2
OchratoxinAhasastrongaffinityforthebrain,especially
c%28c%28Cl%29c1%29C%5B
thecerebellum(Purkinjecells),ventralmesencephalon,and
C%40H%5D%28OC2%3DO%
hippocampalstructures.[13]Theaffinityforthehippocampus
29C%29Cc3ccccc3)
couldberelevanttothepathogenesisofAlzheimer'sdisease,
andsubchronicadministrationtorodentsinduces KEGG C09955(http://www.kegg.jp/en
hippocampalneurodegeneration.Ochratoxincausesacute try/C09955)
depletionofstriataldopamine,whichconstitutesthebedof PubChem 442530(https://pubchem.ncbi.n
Parkinson'sdisease,butitdidnotcausecelldeathinanyof
lm.nih.gov/compound/442530)
brainregionsexamined.[14]TeamsfromZheijiangUniv.and
KielUniv.holdthatochratoxinmaycontributeto InChI
Alzheimer'sandtoParkinson'sdiseases.Nonetheless,their SMILES
studywasperformedinvitroandmaynotextrapolateto Properties
humans.[15]Thedevelopingbrainisverysusceptibleto Chemicalformula C20H18ClNO6
ochratoxin,hencetheneedforcautionduringpregnancy.[16]
Molarmass 403.813
Meltingpoint 169C(336F442K)
Immunosuppressionand Exceptwhereotherwisenoted,dataaregivenfor
immunotoxicity materialsintheirstandardstate(at25C[77F],
100kPa).
OchratoxinAcancauseimmunosuppressionand verify(whatis ?)
immunotoxicityinanimals.Thetoxin'simmunosuppressant
Infoboxreferences
activityinanimalsmayincludedepressedantibody
responses,reducedsizeofimmuneorgans(suchasthe
thymus,spleen,andlymphnodes),changesinimmunecellnumberandfunction,andalteredcytokine
production.Immunotoxicityprobablyresultsfromcelldeathfollowingapoptosisandnecrosis,incombination
withslowreplacementofaffectedimmunecellsduetoinhibitionofproteinsynthesis.[1]

Potentiallinktonephropathies

Balkanendemicnephropathy(BEN),aslowlyprogressiverenaldisease,appearedinthemiddleofthe20th
century,highlylocalizedaroundtheDanube,butonlyhittingcertainhouseholds.Patientsovertheyears
developrenalfailurethatrequiresdialysisortransplantation.Theinitialsymptomsarethoseofa
tubulointerstitialnephritisofthesortmetwithaftertoxicaggressionstotheproximalconvolutedtubules.Such
proximaltubulenephropathiescanbeinducedbyaluminium(e.g.inantiperspirants),antibiotics(vancomycin,
aminosides),tenofovir(forAIDS),andcisplatin.Theirsymptomsarewellknowntonephrologists:glycosuria
withouthyperglycemia,microalbuminuria,poorurineconcentrationcapacity,impairedurineacidification,and
yetlonglastingnormalcreatinineclearance.[17]InBEN,renalbiopsyshowsacellularinterstitialfibrosis,
tubularatrophy,andkaryomegalyinproximalconvolutedtubules.[18]Anumberofdescriptivestudieshave
suggestedacorrelationbetweenexposuretoochratoxinAandBEN,andhavefoundacorrelationbetweenits
geographicaldistributionandahighincidenceof,andmortalityfrom,urothelialurinarytracttumours.[19]
However,insufficientinformationiscurrentlyavailabletoconclusivelylinkochratoxinAtoBEN.[20]Thetoxin
mayrequiresynergisticinteractionswithpredisposinggenotypesorotherenvironmentaltoxicantstoinduce
thisnephropathy.[21]Ochratoxinpossiblyisnotthecauseofthisnephropathy,andmanyauthorsareinfavorof
aristolochicacid,thatiscontainedinaplant:birthwort(Aristolochiaclematitis).Nevertheless,althoughmany
ofthepiecesofscientificevidencearelackingand/orneedseriousreevaluation,itremainsthatochratoxin,in
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pigs,demonstratesdirectcorrelationbetweenexposureandonsetandprogressionofnephropathy.[22]This
porcinenephropathy[23]bearstypicalsignsoftoxicitytoproximaltubules:lossofabilitytoconcentrateurine,
glycosuria,andhistologicalproximaltubuledegeneration.

Othernephropathies,althoughnotrespondingtothe"classical"definitionofBEN,maybelinkedtoochratoxin.
Thus,thiscouldincertaincircumstancesbethecaseforfocalsegmentalglomerulosclerosisafterinhalational
exposure:suchaglomerulopathywithnoteworthyproteinuriahasbeendescribed[24]inpatientswithveryhigh
urinaryochratoxinlevels(around10timeslevelsthatcanbemetwithin"normal"subjects,i.e.around10ppb
or10ng/ml).

Foodanimalindustryimpact

Ochratoxincontaminatedfeedhasitsmajoreconomicimpactonthepoultryindustry.Chickens,turkeys,and
ducklingsaresusceptibletothistoxin.Clinicalsignsofavianochratoxicosisgenerallyinvolvereductionin
weightgains,poorfeedconversion,reducedeggproduction,andpooreggshellquality.[25]Economiclosses
occuralsoinswinefarms,linkedtonephropathyandcostsforthedisposalofcarcasses.

Toxicitydoesnotseemtoconstituteaproblemincattle,astherumenharborsprotozoathathydrolyzeOTA.[26]
However,contaminationofmilkisapossibility.

Dietaryguidelines

EFSAestablishedin2006the"tolerableweekly
intake"(TWI)ofochratoxinA(onadviceofthe
ScientificPanelonContaminantsintheFoodChain)
at120ng/kg.,[27]equivalenttoatolerabledaily
intake(TDI)of14ng/kg.Otherorganizationshave
establishedevenlowerlimitsforintakeof
ochratoxinA,basedontheconsumptionhabitsof
thepopulation.[28]ForUSA,theFDAconsidersa
TDIof5ng/kg.IntheUS,meanbodyweightfor
menis86kg,andforwomen74kg.Hence,theTDI
formenis430ngandforwomenis370ng.Inthe
joinedtable"weightinkg"istheweighteatenper
dayofeachofthelistedfoodstuffs.Diet1,with
smallquantitiesofginger,nutmeg,andpaprika,a
goodservingofdryraisins,areasonableamountof
coffee,cereals,wine,pulses,andsalami,amountsto
asafediet(asforochratoxin,atleast),with286ng
perday.However,itwouldbeeasytogointo
excessivelevels(Diet1+),justbyeating200gof
pigkidneyand200gofpeanuts,whichwouldlead
toatotalofnearly462ngofochratoxin.Thisshows
howdelicateasafedietcanbe.

AlthoughochratoxinAisnotheldasoftodayasresponsibleforrenal
cellcarcinoma(RCC),themostfrequentrenalcancer,itisfrequently
USmeanbodyweight
writtenthatdietarypatternmightdecreaseorincreasetheriskofRCC.
AUruguayancasecontrolstudy[29]correlatesintakeofmeatwith
occurrenceofRCC.AverylargeprospectivecohortinSweden[30]explorescorrelationsbetweenRCC
occurrence,dietsrichinvegetablesandpoultry(socalled"healthydiets"),anddietsrichinmeat(especially
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processedmeat:salami,blackpudding).Thethesisdefendedisthatmorefruitandvegetablesmighthavea
protectiverole.Interestingly,fruit(exceptraisinsanddriedfruit)areverypoorinochratoxin,andprocessed
meatcanberichinochratoxin.
Dermalexposure
OchratoxinAcanpermeatethroughthehumanskin.[31]Althoughnosignificanthealthriskisexpectedafter
dermalcontactinagriculturalorresidentialenvironments,skinexposuretoochratoxinAshouldneverthelessbe
limited.
Seealso
Ochratoxin
References
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"OchratoxinA:Anoverviewontoxicityand
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8.PalmaN,etal.(2007)."OchratoxinAInduced
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11.BasicJukicN,etal.(2007)."Renaltransplantationin
patientswithBalkanendemicnephropathy".
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HolzhauserL.HigginsC.Bezencon(2007).
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Categories: Mycotoxins IARCGroup2Bcarcinogens Isochromenes Lactones Phenols Benzamides

Halogencontainingnaturalproducts Chloroarenes Suspectedtesticulartoxins

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