Developmental Neurotoxicity of Fipronil and Rotenone on a Human Neuronal In Vitro Test System
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| Title: | Developmental Neurotoxicity of Fipronil and Rotenone on a Human Neuronal In Vitro Test System |
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| Authors: | Anne Schmitz, Silke Dempewolf, Saime Tan, Gerd Bicker, Michael Stern |
| Source: | Neurotox Res |
| Publisher Information: | Springer Science and Business Media LLC, 2021. |
| Publication Year: | 2021 |
| Subject Terms: | Neurons, 0301 basic medicine, Insecticides, 0303 health sciences, Dose-Response Relationship, Drug, Neuronal Outgrowth, Cell Differentiation, Cell Line, 3. Good health, 03 medical and health sciences, Dose-Response Relationship, Drug [MeSH], Cell Differentiation/physiology [MeSH], Cell Movement/physiology [MeSH], Humans [MeSH], Neurons/metabolism [MeSH], Cell Differentiation/drug effects [MeSH], Cell Line [MeSH], Neuronal Outgrowth/drug effects [MeSH], Cell Movement/drug effects [MeSH], NT2, Neurite outgrowth, Pyrazoles/toxicity [MeSH], Neurons/drug effects [MeSH], Rotenone/toxicity [MeSH], Neurotoxicity Syndromes/pathology [MeSH], Original Article, Insecticides/toxicity [MeSH], Migration, Neuronal Outgrowth/physiology [MeSH], NTera-2, Neurons/pathology [MeSH], Neurotoxicity Syndromes/metabolism [MeSH], DNT, Differentiation, Cell Movement, Rotenone, Humans, Pyrazoles, Neurotoxicity Syndromes |
| Description: | Pesticide exposure during in utero and early postnatal development can cause a wide range of neurological defects. However, relatively few insecticides have been recognized as developmental neurotoxicants, so far. Recently, discovery of the insecticide, fipronil, in chicken eggs has raised public concern. The status of fipronil as a potential developmental neurotoxicant is still under debate. Whereas several in vivo and in vitro studies suggest specific toxicity, other in vitro studies could not confirm this concern. Here, we tested fipronil and its main metabolic product, fipronil sulfone both at concentrations between 1.98 and 62.5 µM, alongside with the established developmental neurotoxicant, rotenone (0.004–10 µM) in vitro on the human neuronal precursor cell line NT2. We found that rotenone impaired all three tested DNT endpoints, neurite outgrowth, neuronal differentiation, and precursor cell migration in a dose-dependent manner and clearly separable from general cytotoxicity in the nanomolar range. Fipronil and fipronil sulfone specifically inhibited cell migration and neuronal differentiation, but not neurite outgrowth in the micromolar range. The rho-kinase inhibitor Y-27632 counteracted inhibition of migration for all three compounds (EC50 between 12 and 50 µM). The antioxidant, n-acetyl cysteine, could ameliorate the inhibitory effects of fipronil on all three tested endpoints (EC 50 between 84 and 164 µM), indicating the involvement of oxidative stress. Fipronil sulfone had a stronger effect than fipronil, confirming the importance to test metabolic products alongside original pesticides. We conclude that in vitro fipronil and fipronil sulfone display specific developmental neurotoxicity on developing human model neurons. |
| Document Type: | Article Other literature type |
| Language: | English |
| ISSN: | 1476-3524 1029-8428 |
| DOI: | 10.1007/s12640-021-00364-8 |
| Access URL: | https://link.springer.com/content/pdf/10.1007/s12640-021-00364-8.pdf https://pubmed.ncbi.nlm.nih.gov/33871813 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275550 https://link.springer.com/article/10.1007/s12640-021-00364-8 https://europepmc.org/article/MED/33871813 https://link.springer.com/content/pdf/10.1007/s12640-021-00364-8.pdf https://www.ncbi.nlm.nih.gov/pubmed/33871813 https://pubmed.ncbi.nlm.nih.gov/33871813/ https://repository.publisso.de/resource/frl:6444214 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . |
| Accession Number: | edsair.doi.dedup.....5e76a2a1401aa2211241ea3941d65714 |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | Pesticide exposure during in utero and early postnatal development can cause a wide range of neurological defects. However, relatively few insecticides have been recognized as developmental neurotoxicants, so far. Recently, discovery of the insecticide, fipronil, in chicken eggs has raised public concern. The status of fipronil as a potential developmental neurotoxicant is still under debate. Whereas several in vivo and in vitro studies suggest specific toxicity, other in vitro studies could not confirm this concern. Here, we tested fipronil and its main metabolic product, fipronil sulfone both at concentrations between 1.98 and 62.5 µM, alongside with the established developmental neurotoxicant, rotenone (0.004–10 µM) in vitro on the human neuronal precursor cell line NT2. We found that rotenone impaired all three tested DNT endpoints, neurite outgrowth, neuronal differentiation, and precursor cell migration in a dose-dependent manner and clearly separable from general cytotoxicity in the nanomolar range. Fipronil and fipronil sulfone specifically inhibited cell migration and neuronal differentiation, but not neurite outgrowth in the micromolar range. The rho-kinase inhibitor Y-27632 counteracted inhibition of migration for all three compounds (EC50 between 12 and 50 µM). The antioxidant, n-acetyl cysteine, could ameliorate the inhibitory effects of fipronil on all three tested endpoints (EC 50 between 84 and 164 µM), indicating the involvement of oxidative stress. Fipronil sulfone had a stronger effect than fipronil, confirming the importance to test metabolic products alongside original pesticides. We conclude that in vitro fipronil and fipronil sulfone display specific developmental neurotoxicity on developing human model neurons. |
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| ISSN: | 14763524 10298428 |
| DOI: | 10.1007/s12640-021-00364-8 |