{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:49:12Z","timestamp":1768441752424,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["BfR-CPS-08-1334-230, 01DH17052"],"award-info":[{"award-number":["BfR-CPS-08-1334-230, 01DH17052"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003009","name":"Science and Technology Development Fund","doi-asserted-by":"publisher","award":["STDF\u2013DAAD 23052"],"award-info":[{"award-number":["STDF\u2013DAAD 23052"]}],"id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008751","name":"Bundesinstitut f\u00fcr Risikobewertung","doi-asserted-by":"publisher","award":["SFP1322-642"],"award-info":[{"award-number":["SFP1322-642"]}],"id":[{"id":"10.13039\/501100008751","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The interactions between pharmaceuticals and nanomaterials and its potentially resulting toxicological effects in living systems are only insufficiently investigated. In this study, two model compounds, acetaminophen, a pharmaceutical, and cerium dioxide, a manufactured nanomaterial, were investigated in combination and individually. Upon inhalation, cerium dioxide nanomaterials were shown to systemically translocate into other organs, such as the liver. Therefore we picked the human liver cell line HuH-7 cells as an in vitro system to investigate liver toxicity. Possible synergistic or antagonistic metabolic changes after co-exposure scenarios were investigated. Toxicological data of the water soluble tetrazolium (WST-1) assay for cell proliferation and genotoxicity assessment using the Comet assay were combined with an untargeted as well as a targeted lipidomics approach. We found an attenuated cytotoxicity and an altered metabolic profile in co-exposure experiments with cerium dioxide, indicating an interaction of both compounds at these endpoints. Single exposure against cerium dioxide showed a genotoxic effect in the Comet assay. Conversely, acetaminophen exhibited no genotoxic effect. Comet assay data do not indicate an enhancement of genotoxicity after co-exposure. The results obtained in this study highlight the advantage of investigating co-exposure scenarios, especially for bioactive substances.<\/jats:p>","DOI":"10.3390\/ijms22136866","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:07:40Z","timestamp":1624619260000},"page":"6866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Combinatory Effects of Cerium Dioxide Nanoparticles and Acetaminophen on the Liver\u2014A Case Study of Low-Dose Interactions in Human HuH-7 Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4684-2206","authenticated-orcid":false,"given":"Benjamin C.","family":"Krause","sequence":"first","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1536-2840","authenticated-orcid":false,"given":"Fabian L.","family":"Kriegel","sequence":"additional","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"},{"name":"NUVISAN ICB GmbH, Preclinical Compound Profiling, Muellerstrasse 178, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Tartz","sequence":"additional","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Jungnickel","sequence":"additional","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-7727","authenticated-orcid":false,"given":"Ajay Vikram","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Laux","sequence":"additional","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2493-7466","authenticated-orcid":false,"given":"Mohamed","family":"Shemis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Theodor Bilharz Research Institute, Warak El-Hadar, Kornish El-Nile, P.O. Box 30 Imbaba, Giza 12411, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Luch","sequence":"additional","affiliation":[{"name":"Department of Chemical & Product Safety, German Federal Institute for Risk Assessment, Max-Dohrn-Stra\u00dfe 8-10, 10589 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1081\/DMR-200033494","article-title":"Acetaminophen-Induced Hepatotoxicity: Role of Metabolic Activation, Reactive Oxygen\/Nitrogen Species, and Mitochondrial Permeability Transition","volume":"36","author":"Hinson","year":"2004","journal-title":"Drug Metab. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"s104","DOI":"10.7861\/clinmedicine.16-6-s104","article-title":"Drug-induced liver injury","volume":"16","author":"Katarey","year":"2016","journal-title":"Clin. 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