{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:20:49Z","timestamp":1783059649952,"version":"3.54.6"},"reference-count":85,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The chemical exposome is increasingly implicated in neurodegenerative diseases (NDs). However, although human exposure to environmental and dietary contaminants typically occurs as complex mixtures, neurotoxicity assessments still largely focus on single compounds. This study investigated the neurotoxic interactions between aflatoxin B1 (AFB1), acrylamide (ACR), and cadmium in a neuronal cell model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SH\u2010SY5Y cells were exposed to AFB1, ACR, and Cd\n                      <jats:sup>2+<\/jats:sup>\n                      individually or in fixed\u2010ratio mixtures for 72 h. Mixture interactions were evaluated from MTT data using the combination index (CI) approach implemented through the Chou\u2010Talalay (CT) and CISNE frameworks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Individual potency ranked Cd\n                      <jats:sup>2+<\/jats:sup>\n                      &amp;gt;AFB1&amp;gt;ACR. At low effect levels, AFB1\u2010containing mixtures showed relevant deviations from additivity. The ACR\/AFB1 combination displayed synergism at IC10 (CISNE CI 0.62), with concentrations reducing to 4.4\u2010fold for ACR and 2.6\u2010fold for AFB1. AFB1\/Cd\n                      <jats:sup>2+<\/jats:sup>\n                      interactions were model-dependent, with CT indicating synergism at IC10 (CI 0.43), whereas CISNE indicated near additivity. ACR\/Cd\n                      <jats:sup>2+<\/jats:sup>\n                      and ternary mixtures displayed strong antagonism at low effect levels (CISNE CI 7.07 at IC10). Interactions interpretation was generally consistent across models, but CT amplified deviations from additivity at low levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, these findings identify AFB1 as a key contributor to mixture\u2010induced neurotoxicity and support the use of CISNE modelling to improve low\u2010effect interaction analysis in food contaminant risk assessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1857857","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:41:12Z","timestamp":1783057272000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Aflatoxin B1 modulates mixture-induced neurotoxicity under multi-contaminant exposure: insights from combination modeling in SH-SY5Y cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Helena","family":"Ramos","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto","place":["Porto, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Margarida","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto","place":["Porto, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel M. P. L. V. O.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto","place":["Porto, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Faria","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Faculty of Pharmacy, University of Porto","place":["Porto, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s44339-024-00013-7","article-title":"A scoping review on mycotoxin-induced neurotoxicity","volume":"2","author":"Abia","year":"2025","journal-title":"Discov. 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