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dc.contributor.authorBuchmueller, Julia
dc.contributor.authorSprenger, Heike
dc.contributor.authorEbmeyer, Johanna
dc.contributor.authorRasinger, Josef
dc.contributor.authorCreutzenberg, Otto
dc.contributor.authorSchaudien, Dirk
dc.contributor.authorHengstler, Jan G.
dc.contributor.authorGuenther, Georgia
dc.contributor.authorBraeuning, Albert
dc.contributor.authorHessel-Pras, Stefanie
dc.date.accessioned2022-03-07T10:31:54Z
dc.date.available2022-03-07T10:31:54Z
dc.date.created2022-02-10T20:37:22Z
dc.date.issued2021
dc.identifier.citationArchives of Toxicology. 2021, 95 (8), 2785-2796.en_US
dc.identifier.issn0340-5761
dc.identifier.urihttps://hdl.handle.net/11250/2983366
dc.description.abstractPyrrolizidine alkaloids (PAs) are secondary plant metabolites synthesized by a wide range of plants as protection against herbivores. These toxins are found worldwide and pose a threat to human health. PAs induce acute effects like hepatic sinusoidal obstruction syndrome and pulmonary arterial hypertension. Moreover, chronic exposure to low doses can induce cancer and liver cirrhosis in laboratory animals. The mechanisms causing hepatotoxicity have been investigated previously. However, toxic effects in the lung are less well understood, and especially data on the correlation effects with individual chemical structures of different PAs are lacking. The present study focuses on the identification of gene expression changes in vivo in rat lungs after exposure to six structurally different PAs (echimidine, heliotrine, lasiocarpine, senecionine, senkirkine, and platyphylline). Rats were treated by gavage with daily doses of 3.3 mg PA/kg bodyweight for 28 days and transcriptional changes in the lung and kidney were investigated by whole-genome microarray analysis. The results were compared with recently published data on gene regulation in the liver. Using bioinformatics data mining, we identified inflammatory responses as a predominant feature in rat lungs. By comparison, in liver, early molecular consequences to PAs were characterized by alterations in cell-cycle regulation and DNA damage response. Our results provide, for the first time, information about early molecular effects in lung tissue after subacute exposure to PAs, and demonstrates tissue-specificity of PA-induced molecular effects.en_US
dc.language.isoengen_US
dc.titlePyrrolizidine alkaloid-induced transcriptomic changes in rat lungs in a 28-day subacute feeding studyen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.pagenumber2785-2796en_US
dc.source.volume95en_US
dc.source.journalArchives of Toxicologyen_US
dc.source.issue8en_US
dc.identifier.doi10.1007/s00204-021-03108-x
dc.identifier.cristin2000234
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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