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Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids

Pyrrolizidine alkaloids (PAs) are produced by various plant species and have been detected as contaminants in food and feed. Monitoring programmes should include PAs that are present in relevant matrices and that exhibit a high toxic potential. The aim of the present study was to use a bioassay-dire...

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Autores principales: Louisse, Jochem, Mulder, Patrick P. J., Gerssen, Arjen, Stoopen, Geert, Rijkers, Deborah, van de Schans, Milou G. M., Peijnenburg, Ad A. C. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217854/
https://www.ncbi.nlm.nih.gov/pubmed/35610518
http://dx.doi.org/10.1007/s00204-022-03308-z
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author Louisse, Jochem
Mulder, Patrick P. J.
Gerssen, Arjen
Stoopen, Geert
Rijkers, Deborah
van de Schans, Milou G. M.
Peijnenburg, Ad A. C. M.
author_facet Louisse, Jochem
Mulder, Patrick P. J.
Gerssen, Arjen
Stoopen, Geert
Rijkers, Deborah
van de Schans, Milou G. M.
Peijnenburg, Ad A. C. M.
author_sort Louisse, Jochem
collection PubMed
description Pyrrolizidine alkaloids (PAs) are produced by various plant species and have been detected as contaminants in food and feed. Monitoring programmes should include PAs that are present in relevant matrices and that exhibit a high toxic potential. The aim of the present study was to use a bioassay-directed analysis approach to identify relevant PAs not yet included in monitoring programmes. To that end, extracts of Heliotropium europaeum and H. popovii were prepared and analysed with LC–MS/MS for the presence of 35 PAs included in monitoring programmes, as well as for genotoxic activity in the HepaRG/γH2AX assay. Europine, heliotrine and lasiocarpine were found to be the most abundant PAs. The extracts showed a higher γH2AX activity than related artificial mixtures of quantified known PAs, which might point to the presence of unknown toxic PAs. The H. europaeum extract was fractionated and γH2AX activities of individual fractions were determined. Fractions were further analysed applying LC–Orbitrap-MS analysis and Compound Discoverer software, identifying various candidate PAs responsible for the non-explained genotoxic activity. Altogether, the results obtained show that bioassay-directed analysis allows identification of candidate PAs that can be included in monitoring programmes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-022-03308-z.
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spelling pubmed-92178542022-06-24 Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids Louisse, Jochem Mulder, Patrick P. J. Gerssen, Arjen Stoopen, Geert Rijkers, Deborah van de Schans, Milou G. M. Peijnenburg, Ad A. C. M. Arch Toxicol Analytical Toxicology Pyrrolizidine alkaloids (PAs) are produced by various plant species and have been detected as contaminants in food and feed. Monitoring programmes should include PAs that are present in relevant matrices and that exhibit a high toxic potential. The aim of the present study was to use a bioassay-directed analysis approach to identify relevant PAs not yet included in monitoring programmes. To that end, extracts of Heliotropium europaeum and H. popovii were prepared and analysed with LC–MS/MS for the presence of 35 PAs included in monitoring programmes, as well as for genotoxic activity in the HepaRG/γH2AX assay. Europine, heliotrine and lasiocarpine were found to be the most abundant PAs. The extracts showed a higher γH2AX activity than related artificial mixtures of quantified known PAs, which might point to the presence of unknown toxic PAs. The H. europaeum extract was fractionated and γH2AX activities of individual fractions were determined. Fractions were further analysed applying LC–Orbitrap-MS analysis and Compound Discoverer software, identifying various candidate PAs responsible for the non-explained genotoxic activity. Altogether, the results obtained show that bioassay-directed analysis allows identification of candidate PAs that can be included in monitoring programmes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00204-022-03308-z. Springer Berlin Heidelberg 2022-05-24 2022 /pmc/articles/PMC9217854/ /pubmed/35610518 http://dx.doi.org/10.1007/s00204-022-03308-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Analytical Toxicology
Louisse, Jochem
Mulder, Patrick P. J.
Gerssen, Arjen
Stoopen, Geert
Rijkers, Deborah
van de Schans, Milou G. M.
Peijnenburg, Ad A. C. M.
Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
title Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
title_full Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
title_fullStr Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
title_full_unstemmed Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
title_short Bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
title_sort bioassay-directed analysis-based identification of relevant pyrrolizidine alkaloids
topic Analytical Toxicology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217854/
https://www.ncbi.nlm.nih.gov/pubmed/35610518
http://dx.doi.org/10.1007/s00204-022-03308-z
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