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Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro

Phytochemicals 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....

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Autores principales: Buchmueller, Julia, Kaltner, Florian, Gottschalk, Christoph, Maares, Maria, Braeuning, Albert, Hessel-Pras, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408898/
https://www.ncbi.nlm.nih.gov/pubmed/36012484
http://dx.doi.org/10.3390/ijms23169214
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author Buchmueller, Julia
Kaltner, Florian
Gottschalk, Christoph
Maares, Maria
Braeuning, Albert
Hessel-Pras, Stefanie
author_facet Buchmueller, Julia
Kaltner, Florian
Gottschalk, Christoph
Maares, Maria
Braeuning, Albert
Hessel-Pras, Stefanie
author_sort Buchmueller, Julia
collection PubMed
description Phytochemicals 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.
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spelling pubmed-94088982022-08-26 Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro Buchmueller, Julia Kaltner, Florian Gottschalk, Christoph Maares, Maria Braeuning, Albert Hessel-Pras, Stefanie Int J Mol Sci Article Phytochemicals 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. MDPI 2022-08-16 /pmc/articles/PMC9408898/ /pubmed/36012484 http://dx.doi.org/10.3390/ijms23169214 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Buchmueller, Julia
Kaltner, Florian
Gottschalk, Christoph
Maares, Maria
Braeuning, Albert
Hessel-Pras, Stefanie
Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro
title Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro
title_full Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro
title_fullStr Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro
title_full_unstemmed Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro
title_short Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro
title_sort structure-dependent toxicokinetics of selected pyrrolizidine alkaloids in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9408898/
https://www.ncbi.nlm.nih.gov/pubmed/36012484
http://dx.doi.org/10.3390/ijms23169214
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