ReviewOxidativeStressandRedox-ModulatingTherapeuticsinInflammatoryBowelDiseaseArnoR.Bourgonje,1,*MartinFeelisch,2KlaasNicoFaber,1AndreasPasch,3GerardDijkstra,1andHarryvanGoor4Inflammatoryboweldisease(IBD)isassociatedwiththeproductionofreactivespe-ciesthattargetcysteineredoxswitchesinproteins,therebyaffectinggeneregula-tion,DNAdamage,iontransport,intermediarymetabolism,andmitochondrialfunction.Precursorsofreactivespeciesarederivedfromorganicandinorganiccompoundsandtheircofactors,includingaminoacids,vitamins,oxygen,nitrite,andsulfate.Nutritionandthegutmicrobiomefuelthisprocesstoasignificantextent.TheproductionofreactivespeciesinIBDisreflectedbyareductioninsystemicfreethiols,themajorcomponentsoftheantioxidantmachinery.Systemicfreethiolsareamenabletonutritionalortherapeuticintervention.ThisopensupfutureavenuesfortherapeuticmodulationofredoxstatusinIBD.InflammatoryBowelDiseaseandtheRoleofReactiveSpeciesIBDincludestwochronic,progressiveinflammatorydisordersaffectingthegastrointestinal(GI)tract:Crohn’sdisease(CD)andulcerativecolitis(UC).Botharecharacterizedbyinflammationofthegutmucosacausedbyaninappropriateimmuneresponsetriggeredbythegutmicrobiomeingeneticallysusceptibleindividuals[1].TheincidenceofIBDissteadilyincreasinginwesternizedcountries,similarlyinmenandwomen,butvarieswithethnicity[2].Causativefactorsremainunclear,butrecentemphasisontheexposome(seeGlossary)highlightsconsiderationsofacrit-icalinterfacebetweenchemistryandbiology[3].Theexposomeconceptaimstocapturebiologicalresponsestoexposuretophysicalfactorsandsyntheticchemicalsinourenvironment,aswellastodietaryconstituentsandpsychosocialstressorsfromconceptiontodeath,allofwhicharebelievedtocontributetothedevelopmentofchronicmetabolicinflammation(metaflammation)[4–6].TheclinicalsignsandsymptomsofIBDincludeabdominalpain,fatigue,diarrhea,weightloss,andseveralextraintestinalmanifestations(e.g.,arthritis,uveitis,andskindisease).Symptomatologyisoftennon-specific,andpatientsfrequentlysufferfromlong-lastingsubclinicaldi...
