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Of late, transporter\u2010mediated uptake and transport has advanced as a vital determinant of PA toxicity. In this study, the authors investigate a transporter\u2010mediated uptake of PAs and its implications in PA toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>We show that transporter expression levels are significantly affected by treatment with the PAs senecionine (Sc) and retrorsine (Re) in the human hepatoma cell line HepaRG. Furthermore, the specific contribution to PA uptake of the two transporters Na<jats:sup>+<\/jats:sup>\/taurocholate co\u2010transporting polypeptide (SLC10A1) and organic cation transporter I (SLC22A1), both belonging to the heterogeneous solute carrier super family, is investigated by means of a siRNA\u2010mediated knockdown approach. Knockdown of both uptake transporters result in reduced uptake of Re and Sc in a time\u2010dependent manner and attenuated PA\u2010mediated cytotoxic effects in HepaRG cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results confirm previous findings of active transport mechanisms of PAs into hepatocytes and highlight the importance of toxicokinetic studies for the risk assessment of PAs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.202100800","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T13:43:48Z","timestamp":1637934228000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Organic Cation Transporter I and Na<sup>+<\/sup>\/taurocholate Co\u2010Transporting Polypeptide are Involved in Retrorsine\u2010 and Senecionine\u2010Induced Hepatotoxicity in HepaRG cells"],"prefix":"10.1002","volume":"66","author":[{"given":"Anne\u2010Margarethe","family":"Enge","sequence":"first","affiliation":[{"name":"German Federal Institute for Risk Assessment  Max\u2010Dohrn\u2010Str. 8\u201310 10589 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Kaltner","sequence":"additional","affiliation":[{"name":"Chair of Food Safety and Analytics Ludwig Maximilian University of Munich  Schoenleutnerstr. 8 85764 Oberschleissheim Germany"},{"name":"Institute of Food Chemistry and Food Biotechnology Justus Liebig University of Giessen  Heinrich\u2010Buff\u2010Ring 17\u201019 35392 Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Gottschalk","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment  Max\u2010Dohrn\u2010Str. 8\u201310 10589 Berlin Germany"},{"name":"Chair of Food Safety and Analytics Ludwig Maximilian University of Munich  Schoenleutnerstr. 8 85764 Oberschleissheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Kin","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment  Max\u2010Dohrn\u2010Str. 8\u201310 10589 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kirstgen","sequence":"additional","affiliation":[{"name":"Biomedical Research Center Seltersberg (BFS) Faculty of Veterinary Medicine Justus Liebig University of Giessen  Schubertstr. 81 35392 Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Geyer","sequence":"additional","affiliation":[{"name":"Biomedical Research Center Seltersberg (BFS) Faculty of Veterinary Medicine Justus Liebig University of Giessen  Schubertstr. 81 35392 Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"These","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment  Max\u2010Dohrn\u2010Str. 8\u201310 10589 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Hammer","sequence":"additional","affiliation":[{"name":"Signatope GmbH  Markwiesenstr. 55 72770 Reutlingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"P\u00f6tz","sequence":"additional","affiliation":[{"name":"Signatope GmbH  Markwiesenstr. 55 72770 Reutlingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Braeuning","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment  Max\u2010Dohrn\u2010Str. 8\u201310 10589 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6153-0035","authenticated-orcid":false,"given":"Stefanie","family":"Hessel\u2010Pras","sequence":"additional","affiliation":[{"name":"German Federal Institute for Risk Assessment  Max\u2010Dohrn\u2010Str. 8\u201310 10589 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00303957"},{"key":"e_1_2_9_2_1","volume-title":"Chemistry and toxicology of pyrrolizidine alkaloids","author":"Mattocks A.","year":"1986"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf00107a018"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/19440049.2017.1382726"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/19440049.2014.964337"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X92000291"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12030155"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/19440049.2018.1430901"},{"key":"e_1_2_9_9_1","first-page":"95","volume":"8","author":"Stegelmeier B. 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