Perfluoroalkylated Compounds Induce Cell Death and Formation of Reactive Oxygen Species in Cultured Cerebellar Granule Cells
Abstract
The present communication investigates the effects of different perfluoroalkylated compounds (PFCs) on formation of reactive oxygen species (ROS) and cell death in cultured cerebellar granule cells. This allows direct comparison with similar effects found for other environmental contaminants like polychlorinated biphenyls and brominated flame-retardants. The increase in ROS formation and cell death was assayed using the fluorescent probe 2,7-dichlorofluorescin diacetate (DCFH-DA) and the trypan blue exclusion assay. The effects of the PFCs were structure dependent. Cell death was induced at relatively low concentrations by perfluorooctyl sulfonate (PFOS), perfluorooctane sulfonylamide (PFOSA) and the fluorotelomer alcohol 1H, 1H, 2H, 2H-perfluorodecanol (FTOH 8:2) with EC(50)-values of 62 ± 7.6, 13 ± 1.8 and 15 ± 4.2 μM (mean ± SD) respectively. PFOS, perfluorooctanoic acid (PFOA) and PFOSA induced a concentration dependent increase in ROS formation with EC(50)-values of 27 ± 9.0, 25 ± 11 and 57 ± 19μM respectively. Reduced cell viability and ROS formation were observed at concentration level close to what is found in serum of occupationally exposed workers. The effect of PFCs on ROS formation and cell viability was compared with other halogenated compounds and future investigations should emphasize effects of mixtures and how physical chemical properties of the compounds influence their toxicity.
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Although actin filament remodeling has only been demonstrated in response to PFOS exposure, several other in vitro studies have demonstrated the ability of PFOS, PFOA, and PFOSA to generate reactive oxygen species in neurons and astrocytes.
“Whereas this actin filament remodeling has only been demonstrated in response to PFOS exposure, several other in vitro studies have also demonstrated the ability of PFOS, PFOA, and PFOSA, to generate ROS in neurons and astrocytes (Lee et al., 2012; Reistad et al., 2013; Chen et al., 2014; Li Z. et al., 2017).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Reistad et al., 2013
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The Toxicity of Perfluoroalkyl Acids in Zebrafish (Danio rerio)
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- Authors
- Reistad, T., Fonnum, F., & Mariussen, E.
- Affiliations
- Norwegian Defence Research Establishment (NO)
- University of Oslo (NO)
- Corresponding author
- Mariussen, Espen
- ORCID
- Mariussen, Espen
- Venue
- Toxicology Letters
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 218
- Issue
- 1
- Pages
- 56-60
- ISSN
- 0378-4274 (ISSN-L)
- OpenAlex
- W2083002282
- Cited by
- 61
- References
- 46
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 2 · 2022: 7 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 3 · 2013: 2
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Norges Forskningsråd
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Fluorine in Organic Chemistry
- Keywords
- reactive oxygen species, cell death, cerebellar granule cells, perfluorooctanoic acid, fluorotelomer alcohols, halogenated contaminants, occupational exposure, neurotoxicity
- MeSH terms
- Animals, Animals, Suckling, Caprylates, Cell Survival, Cells, Cultured, Cerebellum, Cytoplasmic Granules, Environmental Pollutants, Fluorocarbons, Hydrocarbons, Fluorinated, Structure-Activity Relationship, Sulfonamides, Cell Death, Reactive Oxygen Species, Alkanesulfonic Acids, Oxidative Stress, Rats
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