PMID- 31561889 OWN - NLM STAT- MEDLINE DCOM- 20200323 LR - 20210920 IS - 1879-3592 (Electronic) IS - 1383-5718 (Linking) VI - 845 DP - 2019 Sep TI - Assessment of oxidative damage induced by iron oxide nanoparticles on different nervous system cells. PG - 402989 LID - S1383-5718(18)30271-7 [pii] LID - 10.1016/j.mrgentox.2018.11.013 [doi] AB - Iron oxide nanoparticles (ION) have received much attention for their utility in biomedical applications, such as magnetic resonance imaging, drug delivery and hyperthermia, but concerns regarding their potential harmful effects are also growing. Even though ION may induce different toxic effects in a wide variety of cell types and animal systems, there is a notable lack of toxicological data on the human nervous system, particularly important given the increasing number of applications on this specific system. An important mechanism of nanotoxicity is reactive oxygen species (ROS) generation and oxidative stress. On this basis, the main objective of this work was to assess the oxidative potential of silica-coated (S-ION) and oleic acid-coated (O-ION) ION on human SH-SY5Y neuronal and A172 glial cells. To this aim, ability of ION to generate ROS (both in the absence and presence of cells) was determined, and consequences of oxidative potential were assessed (i) on DNA by means of the 8-oxo-7,8-dihydroguanine DNA glycosylase (OGG1)-modified comet assay, and (ii) on antioxidant reserves by analyzing ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Conditions tested included a range of concentrations, two exposure times (3 and 24 h), and absence and presence of serum in the cell culture media. Results confirmed that, even though ION were not able to produce ROS in acellular environments, ROS formation was increased in the neuronal and glial cells by ION exposure, and was parallel to induction of oxidative DNA damage and, only in the case of neuronal cells treated with S-ION, to decreases in the GSH/GSSG ratio. Present findings suggest the production of oxidative stress as a potential action mechanism leading to the previously reported cellular effects, and indicate that ION may pose a health risk to human nervous system cells by generating oxidative stress, and thus should be used with caution. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Fernandez-Bertolez, Natalia AU - Fernandez-Bertolez N AD - Universidade da Coruna, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigacion, Campus Elvina s/n, 15071-A Coruna, Spain; Universidade da Coruna, Department of Cell and Molecular Biology, Facultad de Ciencias, Campus A Zapateira s/n, 15071-A Coruna, Spain. FAU - Costa, Carla AU - Costa C AD - Portuguese National Institute of Health, Department of Environmental Health, Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal; Universidade do Porto, EPIUnit - Instituto de Saude Publica, Rua das Taipas, 135, 4050-600 Porto, Portugal. FAU - Bessa, Maria Joao AU - Bessa MJ AD - Portuguese National Institute of Health, Department of Environmental Health, Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal; Universidade do Porto, EPIUnit - Instituto de Saude Publica, Rua das Taipas, 135, 4050-600 Porto, Portugal. FAU - Park, Margriet AU - Park M AD - Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. FAU - Carriere, Marie AU - Carriere M AD - Univ. Grenoble-Alpes, CEA, CNRS, INAC-SyMMES, Chimie Interface Biologie pour l'Environnement, la Sante et la Toxicologie (CIBEST), 38000 Grenoble, France. FAU - Dussert, Fanny AU - Dussert F AD - Univ. Grenoble-Alpes, CEA, CNRS, INAC-SyMMES, Chimie Interface Biologie pour l'Environnement, la Sante et la Toxicologie (CIBEST), 38000 Grenoble, France. FAU - Teixeira, Joao Paulo AU - Teixeira JP AD - Portuguese National Institute of Health, Department of Environmental Health, Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal; Universidade do Porto, EPIUnit - Instituto de Saude Publica, Rua das Taipas, 135, 4050-600 Porto, Portugal. FAU - Pasaro, Eduardo AU - Pasaro E AD - Universidade da Coruna, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigacion, Campus Elvina s/n, 15071-A Coruna, Spain. FAU - Laffon, Blanca AU - Laffon B AD - Universidade da Coruna, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigacion, Campus Elvina s/n, 15071-A Coruna, Spain. Electronic address: blaffon@udc.es. FAU - Valdiglesias, Vanessa AU - Valdiglesias V AD - Universidade da Coruna, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Edificio de Servicios Centrales de Investigacion, Campus Elvina s/n, 15071-A Coruna, Spain; Universidade do Porto, EPIUnit - Instituto de Saude Publica, Rua das Taipas, 135, 4050-600 Porto, Portugal. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181130 PL - Netherlands TA - Mutat Res Genet Toxicol Environ Mutagen JT - Mutation research. Genetic toxicology and environmental mutagenesis JID - 101632149 RN - 0 (Culture Media, Serum-Free) RN - 0 (Magnetite Nanoparticles) RN - 0 (Reactive Oxygen Species) RN - 2UMI9U37CP (Oleic Acid) RN - 7631-86-9 (Silicon Dioxide) RN - EC 3.2.2.- (DNA Glycosylases) RN - EC 3.2.2.- (oxoguanine glycosylase 1, human) RN - GAN16C9B8O (Glutathione) SB - IM MH - Cell Line, Tumor MH - Culture Media, Serum-Free MH - DNA Damage MH - DNA Glycosylases/pharmacology MH - Dose-Response Relationship, Drug MH - Glioblastoma/pathology MH - Glutathione/metabolism MH - Humans MH - Magnetite Nanoparticles/chemistry/*toxicity MH - Neuroblastoma/pathology MH - Neuroglia/*drug effects MH - Neurons/*drug effects MH - Oleic Acid MH - Oxidation-Reduction MH - *Oxidative Stress MH - Particle Size MH - Reactive Oxygen Species MH - Silicon Dioxide MH - Surface Properties OTO - NOTNLM OT - A172 Cells OT - Glutathione depletion OT - Iron oxide nanoparticles OT - Oxidative DNA damage OT - Reactive oxygen species OT - SH-SY5Y cells EDAT- 2019/09/29 06:00 MHDA- 2020/03/24 06:00 CRDT- 2019/09/29 06:00 PHST- 2018/07/24 00:00 [received] PHST- 2018/11/02 00:00 [revised] PHST- 2018/11/29 00:00 [accepted] PHST- 2019/09/29 06:00 [entrez] PHST- 2019/09/29 06:00 [pubmed] PHST- 2020/03/24 06:00 [medline] AID - S1383-5718(18)30271-7 [pii] AID - 10.1016/j.mrgentox.2018.11.013 [doi] PST - ppublish SO - Mutat Res Genet Toxicol Environ Mutagen. 2019 Sep;845:402989. doi: 10.1016/j.mrgentox.2018.11.013. Epub 2018 Nov 30.