ArticleArchives of toxicology2019
Development of a neurotoxicity assay that is tuned to detect mitochondrial toxicants.
Article in Archives of toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Complex Distribution Phenomena and Plastic Binding of Test Chemicals in Cell Culture Experiments: Exemplification by Tebufenpyrad.International journal of molecular sciences · 2026Article
- Leveraging Consensus Docking Approaches for Human Mitochondrial Complexes I and III.Chemical research in toxicology · 2026Article
- Article
- Testing Strategies for Metabolite-Mediated Neurotoxicity.International journal of molecular sciences · 2025Review
- 2024 International Academy of Toxicologic Pathology (IATP) Satellite Symposium: New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives.Toxicologic pathology · 2025Article
- Programmed neurite degeneration in human central nervous system neurons driven by changes in NADCell death & disease · 2025Article
- Inhibition of Neural Crest Cell Migration by Strobilurin Fungicides and Other Mitochondrial Toxicants.Cells · 2024Article
- Cellular and Mitochondrial Toxicity of Tolcapone, Entacapone, and New Nitrocatechol Derivatives.ACS pharmacology & translational science · 2024Article
- New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project.Frontiers in toxicology · 2024Article
- Definition of the Neurotoxicity-Associated Metabolic Signature Triggered by Berberine and Other Respiratory Chain Inhibitors.Antioxidants (Basel, Switzerland) · 2023Article
- Identification of the bacterial metabolite aerugine as potential trigger of human dopaminergic neurodegeneration.Environment international · 2023Article
- G × E interactions as a basis for toxicological uncertainty.Archives of toxicology · 2023Article
- Dynamic Metabolic and Transcriptional Responses of Proteasome-Inhibited Neurons.Antioxidants (Basel, Switzerland) · 2023Article
- Assessing Drug-Induced Mitochondrial Toxicity in Cardiomyocytes: Implications for Preclinical Cardiac Safety Evaluation.Pharmaceutics · 2022Review
- Article
- Inhibition of neurite outgrowth and enhanced effects compared to baseline toxicity in SH-SY5Y cells.Archives of toxicology · 2022Article
- Metabolic Reprogramming in HIV-Associated Neurocognitive Disorders.Frontiers in cellular neuroscience · 2022Article
- Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation.Archives of toxicology · 2022Article
- Mild pentachlorophenol-mediated uncoupling of mitochondria depletes ATP but does not cause an oxidized redox state or dopaminergic neurodegeneration inCurrent research in toxicology · 2022Article
- Acute effects of the imidacloprid metabolite desnitro-imidacloprid on human nACh receptors relevant for neuronal signaling.Archives of toxicology · 2021Article
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Authors and funding
13 authors.
Funding
Abstract
Many neurotoxicants affect energy metabolism in man, but currently available test methods may still fail to predict mito- and neurotoxicity. We addressed this issue using LUHMES cells, i.e., human neuronal precursors that easily differentiate into mature neurons. Within the NeuriTox assay, they have been used to screen for neurotoxicants. Our new approach is based on culturing the cells in either glucose or galactose (Glc-Gal-NeuriTox) as the main carbohydrate source during toxicity testing. Using this Glc-Gal-NeuriTox assay, 52 mitochondrial and non-mitochondrial toxicants were tested. The panel of chemicals comprised 11 inhibitors of mitochondrial respiratory chain complex I (cI), 4 inhibitors of cII, 8 of cIII, and 2 of cIV; 8 toxicants were included as they are assumed to be mitochondrial uncouplers. In galactose, cells became more dependent on mitochondrial function, which made them 2-3 orders of magnitude more sensitive to various mitotoxicants. Moreover, galactose enhanced the specific neurotoxicity (destruction of neurites) compared to a general cytotoxicity (plasma membrane lysis) of the toxicants. The Glc-Gal-NeuriTox assay worked particularly well for inhibitors of cI and cIII, while the toxicity of uncouplers and non-mitochondrial toxicants did not differ significantly upon glucose ↔ galactose exchange. As a secondary assay, we developed a method to quantify the inhibition of all mitochondrial respiratory chain functions/complexes in LUHMES cells. The combination of the Glc-Gal-NeuriTox neurotoxicity screening assay with the mechanistic follow up of target site identification allowed both, a more sensitive detection of neurotoxicants and a sharper definition of the mode of action of mitochondrial toxicants.
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