Table Of ContentBiomarkers in Disease: Methods,
Discoveries and Applications
SeriesEditors
VinoodB.Patel,SchoolofLifeSciences,UniversityofWestminster,London,UK
VictorR.Preedy,SchoolofLifeCourseandPopulationSciences,FacultyofLife
SciencesandMedicine,King’sCollegeLondon,London,UK
Inthepastdecadetherehasbeenamajorseachangeinthewaydiseaseisdiagnosed
andinvestigatedduetotheadventofhighthroughputtechnologies,suchasmicro-
arrays, lab on a chip, proteomics, genomics, lipomics, metabolomics etc. These
advances haveenabled thediscoveryofnewandnovel markers of diseaserelating
to autoimmune disorders, cancers, endocrine diseases, genetic disorders, sensory
damage, intestinal diseases etc. In many instances these developments have gone
handinhandwiththediscoveryofbiomarkerselucidatedviatraditionalorconven-
tional methods, such as histopathology or clinical biochemistry. Together with
microprocessor-based data analysis, advanced statistics and bioinformatics these
markers have been used to identify individuals with active disease or pathology as
wellasthosewhoarerefractoryorhavedistinguishingpathologies.Newanalytical
methods that have been used to identify markers of disease and is suggested that
there may be as many as 40 different platforms. Unfortunately techniques and
methods have not been readily transferable to other disease states and sometimes
diagnosisstillreliesonsingleanalytesratherthanacohortofmarkers.Thereisthusa
demand for acomprehensive and focused evidenced-based text and scientific liter-
ature that addresses these issues. Hence the formulation of Biomarkers in Disease.
The series covers a wide number of areas including for example, nutrition, cancer,
endocrinology, cardiology, addictions, immunology, birth defects, genetics and so
on.Thechaptersarewrittenbynationalorinternationalexpertsandspecialists.
SeriesTitles
1. GeneralMethodsinBiomarkerResearchandTheirApplications
2. BiomarkersinCancer
3. BiomarkersinCardiovascularDisease
4. BiomarkersinKidneyDisease
5. BiomarkersinBoneDisease
6. BiomarkersinLiverDisease
7. BiomarkersinDiabetes
8. BiomarkersinNutrition
9. BiomarkersinToxicology
10. BiomarkersinTrauma,InjuryandCriticalCare
(cid:129) (cid:129)
Vinood B. Patel Victor R. Preedy
Rajkumar Rajendram
Editors
Biomarkers in Toxicology
With175Figuresand79Tables
Editors
VinoodB.Patel VictorR.Preedy
SchoolofLifeSciences SchoolofLifeCourseandPopulationSciences
UniversityofWestminster FacultyofLifeSciencesandMedicine
London,UK King’sCollegeLondon
London,UK
RajkumarRajendram
CollegeofMedicine
KingSaudbinAbdulazizUniversityfor
HealthSciences
Riyadh,SaudiArabia
ISSN2542-3657 ISSN2542-3665(electronic)
BiomarkersinDisease:Methods,DiscoveriesandApplications
ISBN978-3-031-07391-5 ISBN978-3-031-07392-2(eBook)
https://doi.org/10.1007/978-3-031-07392-2
©SpringerNatureSwitzerlandAG2023
Thisworkissubjecttocopyright.AllrightsaresolelyandexclusivelylicensedbythePublisher,whether
thewholeorpartofthematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseof
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and
transmission or information storage and retrieval, electronic adaptation, computer software, or by
similarordissimilarmethodologynowknownorhereafterdeveloped.
Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthispublication
doesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevant
protectivelawsandregulationsandthereforefreeforgeneraluse.
Thepublisher,theauthors,andtheeditorsaresafetoassumethattheadviceandinformationinthisbook
arebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernortheauthorsorthe
editorsgiveawarranty,expressedorimplied,withrespecttothematerialcontainedhereinorforanyerrors
oromissionsthatmayhavebeenmade.Thepublisherremainsneutralwithregardtojurisdictionalclaims
inpublishedmapsandinstitutionalaffiliations.
ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG.
Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland
Preface
Inrecentyears,therehavebeenmajorchangesinthewaydiseasesarediagnosedand
investigated due to the advent of high-throughput technologies and advances in
chemistry and physics. This has led to the development of microarrays, lab-on-a-
chip, proteomics, genomics, lipomics, metabolomics, and other new platforms.
These advances have enabled the discovery of new and novel markers of disease
relating to autoimmune disorders, cancers, endocrine diseases, genetic disorders,
sensorydamage,intestinaldiseases,andmanyotherconditionstoonumeroustolist
here.Inmanyinstances,theseprogressionshavegonehandinhandwithanalysisof
biomarkers elucidated via traditional methods, such as histopathology, immunoas-
says, and clinical biochemistry. Together with microprocessor-based data analysis,
advanced statistics, and bioinformatics, these markers have been used to identify
individuals with active disease as well as those who are refractory or have
distinguishingpathologies.
Unfortunately,techniquesandmethodshavenotbeenreadilytransferabletoother
diseasestates,andsometimes diagnosisstillreliesonasingleanalyte ratherthan a
cohort of markers. Furthermore, the discovery of many new markers has not been
put into clinical practice partly because of their cost and partly because some
scientists are unaware of their existence or the evidence is at the preclinical stage.
There is thus a demand for a comprehensive and focused evidence-based text that
addresses these issues. Hence the book Biomarkers in Disease: Methods, Discov-
eriesandApplications–BiomarkersinToxicology.Itimpartsholisticinformation
on the scientific basis of health and biomarkers and covers the latest knowledge,
trends, and links with treatments. It links conventional approaches with new
platforms.
Inthepresentbook,BiomarkersinToxicologywehavesectionson:
1. Singlecomponents
2. Panelsandarrays
3. Genetic,cellular,andhistologicalvariables
4. Functionalandphysiologicalvariablesandplatforms
5. Biomarkersinspecificconditionsorscenarios
6. Biomarkersinmodelsandmodelingtoxicity
7. Resources
v
vi Preface
Theabilitytotranscendtheintellectualdivideisaidedbythefactthateachchapter
has:
(cid:129) KeyFacts(areasoffocusexplainedforthelayperson)
(cid:129) DefinitionsofWordsandTerms
(cid:129) ApplicationstoPrognosis,OtherDiseases,orConditions
(cid:129) SummaryPoints
ThematerialinApplicationstoPrognosis,OtherDiseases,orConditionspertains
tospeculativeorproposedareasofresearch,cross-transferencetootherdiseasesor
stagesofthedisease,translationalissues,andotherareasofwideapplicability.
TheEditorsrecognizethedifficultiesinassigningchapterstopartsofthebook,as
some chapters can fit into more than one section. Nevertheless, the book has
enormouslywidecoverageandiswellindexed.
The chapters are written by national and international experts. This book is
designed for toxicologists, pharmacologists, clinical biochemists, health scientists
specializing in drugs of abuse, epidemiologists, researchers, doctors, and nurses,
fromstudentstopractitionersatthehigherlevel.Itisalsodesignedtobesuitablefor
lecturersandteachersinhealthcareandacademiclibrariesasareferenceguide.
London,UK VinoodB.Patel
London,UK VictorR.Preedy
Riyadh,SaudiArabia RajkumarRajendram
January2023
Series Preface
Inthepastdecadetherehavebeenmajorchangesinthewaydiseasesarediagnosed
andinvestigatedduetotheadventofhigh-throughputtechnologiesandadvancesin
chemistry and physics. This has led to the development of microarrays, lab-on-a-
chip, proteomics, genomics, lipomics, metabolomics, and other new platforms.
These advances have enabled the discovery of new and novel markers of disease
relating to autoimmune disorders, cancers, endocrine diseases, genetic disorders,
sensorydamage,intestinaldiseasesandmanyotherconditionstoonumeroustolist
here.Inmanyinstancesthesedevelopmentshavegonehandinhandwithanalysisof
biomarkers elucidated via traditional methods, such as histopathology, immunoas-
says and clinical biochemistry. Together with microprocessor-based data analysis,
advanced statistics and bioinformatics these markers have been used to identify
individuals with active disease as well as those who are refractory or have
distinguishingpathologies.
Unfortunately,techniquesandmethodshavenotbeenreadilytransferabletoother
diseasestates,andsometimes diagnosisstillreliesonasingleanalyte ratherthan a
cohort of markers. Furthermore, the discovery of many new markers has not been
put into clinical practice partly because of their cost and partly because some
scientists are unaware of their existence or the evidence is at the preclinical stage.
Thereisthusademandforacomprehensiveandfocusedevidenced-basedtextthat
addresses these issues. Hence the book series Biomarkers in Disease: Methods,
DiscoveriesandApplications.Itimpartsholisticinformationonthescientificbasis
ofhealthandbiomarkersandcoversthelatestknowledge,trendsandtreatments.It
links conventional approaches with new platforms. The ability to transcend the
intellectualdivideisaidedbythefactthateachchapterhas:
(cid:129) KeyFacts(areasoffocusexplainedforthelayperson)
(cid:129) DefinitionsofWordsandTerms
(cid:129) PotentialApplicationstoPrognosis,OtherDiseasesorConditions
(cid:129) SummaryPoints
The material in Potential Applications to Prognosis, Other Diseases or Condi-
tions pertains to speculative or proposed areas of research, cross-transference to
vii
viii SeriesPreface
other diseases orstagesofthedisease,translationalissues,andother areas ofwide
applicability.
TheSeriesisexpectedtoproveusefulforclinicians,scientists,epidemiologists,
doctorsandnurses,andalsoacademiciansandstudentsatanadvancedlevel.
TheEditors
Contents
PartI SingleComponents .................................. 1
1 SolubleGuanylylCyclaseAlpha1SubunitasaBiomarker
ofToxicity:ApplicationstoInvestigateEndocrine-Disrupting
Chemicals ............................................ 3
MaríaTeresaPinoandJimenaPaulaCabilla
2 SerumParaoxonase1asaBiomarkerinToxicology ........... 25
BaşakGökçe
3 ErythrocyteAcetylcholinesteraseasaBiomarkerof
EnvironmentalLeadExposure ............................ 39
NnennaL.Nwobi,JosephC.Nwobi,RazaqA.Ogunbona,
AdebolaO.Adetunji,andJohnI.Anetor
4 FortilinasaBiomarkerinToxicity ......................... 63
ShreenD.Nusair
5 AntibodiesasBiomarkers:EffectofMicrocystinExposure ...... 85
AlejandroFerrari,MarciaAndreaRuiz,andAnaLauraRuibal-Conti
6 Gamma-H2AXExpressionasaBiomarkerofCarcinogenesis:
ApplicationstoToxicology ............................... 107
ShugoSuzukiandHidekiWanibuchi
7 TheCarcinogenGlycidolandUseofN-(2,3-Dihydroxypropyl)-
valineinHemoglobinasaBiomarkerofExposure ............ 123
BernhardH.MonienandKlausAbraham
8 BiomarkersofAntibioticToxicity:AFocuson
Metronidazole ......................................... 139
MosesW.Bariweni,VinoodB.Patel,GulrezM.Zariwala,and
RaymondI.Ozolua
ix
x Contents
PartII PanelsandArrays ................................. 155
9 Pro-inflammatoryMarkersofEnvironmentalToxicants ........ 157
JasminaDimitrova-Shumkovska,LeoVeenman,and
LjupchoKrstanoski
10 OxidativeStressBiomarkersandTheirApplicationsto
DetectExcessiveFluorine ................................ 177
HalynaTkachenkoandNataliaKurhaluk
11 BiomarkersofAlcoholToxicity ............................ 203
NataliaKurhalukandHalynaTkachenko
12 BiomarkersofLiverInjuryduetoToxicAgents:Progress,
CurrentApplications,andEmergingDirections .............. 223
MitchellR.McGill
13 BiomarkersforAssessingMycotoxinExposureand
HealthEffects ......................................... 243
CarlosAugustoFernandesdeOliveira,LarissaTuannyFranco,and
AmirIsmail
14 MetabolomicsProfilingofDi-(2-propylheptyl)Phthalate(DPHP)
BiotransformationProductsasExposureMarkers:
AnalyticalStrategyandApplication ........................ 271
Shih-WenLi,Chih-WeiChang,Yuan-ChihChen,Jing-FangHsu,and
Pao-ChiLiao
15 BiomarkersofNeurotoxicity .............................. 291
AlicjaMaciejska,AlicjaSkórkowska,JakubJurczyk,
BartoszPomierny,andBogusławaBudziszewska
PartIII Genetic,Cellular,andHistologicalVariables ........... 321
16 GeneticandEpigeneticBiomarkersRelatedto
2-Oxoglutarate/Fe(II)-DependentOxygenasesandImplications
forDiseaseandToxicology ............................... 323
JieWang,RuiQi,HuifangLi,ChristoChristov,NicolaiLehnert,and
DeyuLi
17 DNAAdductsasBiomarkersinToxicology .................. 351
CarlosHernandez-Castillo,SarahC.Shuck,andJohnTermini
18 DNAMethylationasaBiomarkerandApplicationto
Aluminum:ADRB250-UntranslatedRegion(50-UTR)Methylation
Level ................................................ 383
OlaElsayedNafea
