Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro

Simple item page
dc.contributor.authorBuchmueller, Julia
dc.contributor.authorKaltner, Florian
dc.contributor.authorGottschalk, Christoph
dc.contributor.authorMaares, Maria
dc.contributor.authorBraeuning, Albert
dc.contributor.authorHessel-Pras, Stefanie
dc.date.accessioned2022-09-19T11:45:16Z
dc.date.available2022-09-19T11:45:16Z
dc.date.issued2022-08-16
dc.date.updated2022-09-07T15:21:41Z
dc.description.abstractPhytochemicals like pyrrolizidine alkaloids (PAs) can affect the health of humans and animals. PAs can occur for example in tea, honey or herbs. Some PAs are known to be cytotoxic, genotoxic, and carcinogenic. Upon intake of high amounts, hepatotoxic and pneumotoxic effects were observed in humans. This study aims to elucidate different toxicokinetic parameters like the uptake of PAs and their metabolism with in vitro models. We examined the transport rates of differently structured PAs (monoester, open-chained diester, cyclic diester) over a model of the intestinal barrier. After passing the intestinal barrier, PAs reach the liver, where they are metabolized into partially instable electrophilic metabolites interacting with nucleophilic centers. We investigated this process by the usage of human liver, intestinal, and lung microsomal preparations for incubation with different PAs. These results are completed with the detection of apoptosis as indicator for bioactivation of the PAs. Our results show a structure-dependent passage of PAs over the intestinal barrier. PAs are structure-dependently metabolized by liver microsomes and, to a smaller extent, by lung microsomes. The detection of apoptosis of A549 cells treated with lasiocarpine and monocrotaline following bioactivation by human liver or lung microsomes underlines this result. Conclusively, our results help to shape the picture of PA toxicokinetics which could further improve the knowledge of molecular processes leading to observed effects of PAs in vivo.en
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/17498
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-16279
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftende
dc.subject.otherpyrrolizidine alkaloidsen
dc.subject.othermetabolismen
dc.subject.otherstructure-dependencyen
dc.subject.otheruptakeen
dc.titleStructure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitroen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber9214en
dcterms.bibliographicCitation.doi10.3390/ijms23169214en
dcterms.bibliographicCitation.issue16en
dcterms.bibliographicCitation.journaltitleInternational Journal of Molecular Sciencesen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume23en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Lebensmitteltechnologie und Lebensmittelchemie::FG Lebensmittelchemie und Toxikologiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Lebensmittelchemie und Toxikologiede
tub.affiliation.instituteInst. Lebensmitteltechnologie und Lebensmittelchemiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

Files

Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
ijms-23-09214-v3.pdf
Size:
2.47 MB
Format:
Adobe Portable Document Format
Download
No Thumbnail Available
Name:
ijms-23-09214-s001.zip
Size:
256.97 KB
Format:
ZIP archive format.
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
4.86 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Publications