{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T22:41:53Z","timestamp":1776724913375,"version":"3.51.2"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>\n                    Thyroid hormone (TH) availability is particularly critical for early brain development. TH transport across the blood-brain barrier is facilitated through two main transmembrane transporters: monocarboxylate transporter 8 (MCT8) and organic anion transporter 1C1 (OATP1C1). Inhibition of MCT8-mediated TH transport has been identified for a number of environmental chemicals using\n                    <jats:italic>in vitro<\/jats:italic>\n                    screening assays. Here we examined the\n                    <jats:italic>in vivo<\/jats:italic>\n                    effects of exposure to a potent\n                    <jats:italic>in vitro<\/jats:italic>\n                    inhibitor of MCT8, the flavonolignan silychristin, on several aspects of the TH system. Adult female rats were daily gavaged with 0, 250, or 500\u00a0mg\/kg\/day (n = 10\/group) of silychristin for 7 days and euthanized on day 8. A smaller group (n = 5\/group) of rats was administered the related flavonolignan, silybin (900\u00a0mg\/kg), or the milk-thistle-derived flavonolignan mixture, silymarin (1,500\u00a0mg\/kg). Serum TH concentrations were not changed in any treatment group.\n                    <jats:italic>Mct8<\/jats:italic>\n                    and\n                    <jats:italic>Oatp1c1<\/jats:italic>\n                    expression were upregulated in the choroid plexus upon silymarin exposure, without change in response to silychristin or silybin. Deiodinase 1 and dehalogenase activities, unchanged in the liver, were increased in the thyroid by the high dose of silychristin. These changes may have been triggered by increased thyroidal TH content, consequent to a reduction in MCT8-mediated TH efflux. Pharmacokinetic properties of silychristin and other flavonoids result in their low bioavailability and likely contributed to the largely negative findings. These observations demonstrate the challenges in extrapolating results from\n                    <jats:italic>in vitro<\/jats:italic>\n                    models to studies in intact organisms, showcasing the importance of selecting appropriate animal models and the best experimental design for assessing effects on human health.\n                  <\/jats:p>","DOI":"10.3389\/ftox.2026.1796387","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T22:10:13Z","timestamp":1776723013000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Examining in vivo effects of silychristin, a potent in vitro inhibitor of thyroid hormone transporter MCT8"],"prefix":"10.3389","volume":"8","author":[{"given":"Kostja","family":"Renko","sequence":"first","affiliation":[{"name":"BFR German Federal Institute for Risk Assessment, German Centre for the Protection of Laboratory Animals (Bf3R)","place":["Berlin, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryne","family":"Thomas","sequence":"additional","affiliation":[{"name":"Office of Research and Development, Environmental Protection Agency, Research Triangle Park","place":["Durham, NC, United States"]},{"name":"Oak Ridge Institute for Science Education Oak Ridge","place":["Oak Ridge, TN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MaryAnn","family":"Hawks","sequence":"additional","affiliation":[{"name":"Office of Research and Development, Environmental Protection Agency, Research Triangle Park","place":["Durham, NC, United States"]},{"name":"Oak Ridge Institute for Science Education Oak Ridge","place":["Oak Ridge, TN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jermaine","family":"Ford","sequence":"additional","affiliation":[{"name":"Office of Research and Development, Environmental Protection Agency, Research Triangle Park","place":["Durham, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef","family":"K\u00f6hrle","sequence":"additional","affiliation":[{"name":"Charit\u00e9 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, Institut f\u00fcr Experimentelle Endokrinologie","place":["Berlin, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Axelstad","sequence":"additional","affiliation":[{"name":"National Food Institute, Technical University of Denmark","place":["Lyngby, Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary E.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Office of Research and Development, Environmental Protection Agency, Research Triangle Park","place":["Durham, NC, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1089\/thy.2025.0089","article-title":"Inactivation of thyroid hormone transporters Mct8\/Oatp1c1 in mouse brain endothelial cells causes region-specific alterations in central thyroid hormone signaling","volume":"35","author":"Alevyzaki","year":"2025","journal-title":"Thyroid"},{"key":"B2","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/nrendo.2015.186","article-title":"Thyroid hormone transporters--functions and clinical implications","volume":"11","author":"Bernal","year":"2015","journal-title":"Nat. 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