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Fluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue

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dc.abstract.enIn many pharmaceuticals, a hydrogen atom or hydroxyl group is replaced by a fluorine to increase bioavailability and biostability. The fate of fluorine released from fluorine-containing drugs is not well investigated. The aim of this study was to examine possible fluorination of proteins in rat liver and brain after administration of the fluorinated drug cinacalcet. We assigned 18 Wistar rats to a control group (n = 6) and a group treated with cinacalcet (2 mg kg−1/body weight, 5 days/week), divided into 7 day (n = 6) and 21 day (n = 6) treatment subgroups. Fluorinated proteins were identified using a free proteomics approach; chromatographic separation and analysis by high-resolution mass spectrometry; peptide/protein identification using the Mascot search algorithm; manual verification of an experimentally generated MS/MS spectrum with the theoretical MS/MS spectrum of identified fluorinated peptides. Three fluorinated proteins (spectrin beta chain; carbamoyl-phosphate synthase [ammonia], mitochondrial; 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 1) were identified in the liver and four (spectrin beta chain, dihydropyrimidinase-related protein 4, prominin-2, dihydropyrimidinase-related protein 4) in the brain tissue after 21 days of cinacalcet treatment, but not in the control group. Introduction of fluorine into an organism by administration of fluorinated drugs results in tissue-specific fluorination of proteins.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorGawor, Andrzej
dc.contributor.authorBulska, Ewa
dc.contributor.authorKonopka, Anna
dc.contributor.authorPączek, Leszek
dc.contributor.authorWryk, Grzegorz
dc.contributor.authorCzarkowska-Paczek, Bozena
dc.contributor.authorGajewski, Zdzislaw
dc.date.accessioned2024-01-25T01:14:01Z
dc.date.available2024-01-25T01:14:01Z
dc.date.copyright2022-04-11
dc.date.issued2022
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number8
dc.description.versionFINAL_PUBLISHED
dc.description.volume23
dc.identifier.doi10.3390/IJMS23084202
dc.identifier.issn1422-0067
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/107309
dc.identifier.weblinkhttps://www.mdpi.com/1422-0067/23/8/4202/pdf
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.pages4202 (1-11)
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enfluorinated drug
dc.subject.enprotein fluorination
dc.subject.endrug biotransformation
dc.subject.enfluorine
dc.titleFluorine-Containing Drug Administration in Rats Results in Fluorination of Selected Proteins in Liver and Brain Tissue
dc.typeJournalArticle
dspace.entity.typePublication