An adverse outcome pathway-based approach to assess steatotic mixture effects of hepatotoxic pesticides in vitro
| العنوان: | An adverse outcome pathway-based approach to assess steatotic mixture effects of hepatotoxic pesticides in vitro |
|---|---|
| المؤلفون: | Bernd Wollscheid, Roger Rahmani, Anastasia Spyropoulou, Ad A. C. M. Peijnenburg, Dajana Lichtenstein, Geert Stoopen, Georges de Sousa, Jimmy Alarcan, Nathalie Zucchini-Pascal, Efrosini S. Katsanou, Marianna Stamou, Claudia Luckert, Emanuela S. Milani, Kyriaki Machera, Deborah Rijkers, Albert Braeuning, Shana J. Sturla, Parthena Konstantinidou, Michail Gioutlakis, Alfonso Lampen |
| المساهمون: | Bundesinstitut für Risikobewertung - Federal Institute for Risk Assessment (BfR), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Benaki Phytopathological Institute, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Department of Health Sciences and Technology [ETH Zürich] (D-HEST), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Wageningen University and Research [Wageningen] (WUR), European Project: 633172,H2020,H2020-SFS-2014-2,EuroMix(2015), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Benaki Phytopathological Institute (BPI) |
| المصدر: | Food and Chemical Toxicology Food and Chemical Toxicology, Elsevier, 2020, 139, ⟨10.1016/j.fct.2020.111283⟩ Food and Chemical Toxicology, 139 Food and Chemical Toxicology 139 (2020) Food and Chemical Toxicology, 2020, 139, ⟨10.1016/j.fct.2020.111283⟩ |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Key genes, Novel Foods & Agrochains, [SDV]Life Sciences [q-bio], Gene Expression, Receptors, Cytoplasmic and Nuclear, Pharmacology, Toxicology, Novel Foods & Agroketens, chemistry.chemical_compound, Adverse Outcome Pathway, BU Toxicology, Novel Foods & Agrochains, 0303 health sciences, Pesticide mixtures, BU Toxicology, Liver Neoplasms, Imidazoles, 04 agricultural and veterinary sciences, General Medicine, Hep G2 Cells, 040401 food science, 3. Good health, Relative potency factors, BU Toxicologie, Novel Foods & Agroketens, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Drug-Related Side Effects and Adverse Reactions, BU Toxicologie, Cell Survival, Risk Assessment, 03 medical and health sciences, 0404 agricultural biotechnology, Cell Line, Tumor, medicine, Animals, Humans, Pesticides, Triglycerides, 030304 developmental biology, Triglyceride, Triglyceride accumulation, Adverse Outcome Pathways, Clothianidin, Pesticide, medicine.disease, In vitro, Fatty Liver, chemistry, Nuclear receptor, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Steatosis, AOP-Wise testing, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science |
| الوصف: | Exposure to complex chemical mixtures requires a tiered strategy for efficient mixture risk assessment. As a part of the EuroMix project we developed an adverse outcome pathway (AOP)-based assay toolbox to investigate the combined effects of the liver steatosis-inducing compounds imazalil, thiacloprid, and clothianidin in human HepaRG hepatocarcinoma cells. Compound-specific relative potency factors were determined using a benchmark dose approach. Equipotent mixtures were tested for nuclear receptor activation, gene and protein expression, and triglyceride accumulation, according to the molecular initiating events and key events proposed in the steatosis AOP. All three compounds affected the activity of nuclear receptors, but not key genes/proteins as proposed. Triglyceride accumulation was observed with three different methods. Mixture effects were in agreement with the assumption of dose additivity for all the combinations and endpoints tested. Compound-specific RPFs remained similar over the different endpoints studied downstream the AOP. Therefore, it might be possible to reduce testing to a smaller battery of key tests. The results demonstrate the suitability of our in vitro assay toolbox, integrated within an AOP framework and combined with the RPF approach, for the analysis of steatotic effects of chemical mixtures. However, mRNA results suggest that the steatosis AOP still needs improvement. |
| وصف الملف: | application/octet-stream; application/pdf |
| تدمد: | 1873-6351 0278-6915 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c4313079920eeabf454f75d1402891f https://pubmed.ncbi.nlm.nih.gov/32201337 |
| حقوق: | RESTRICTED |
| رقم الأكسشن: | edsair.doi.dedup.....1c4313079920eeabf454f75d1402891f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18736351 02786915 |
|---|