ArticleEnvironmental health perspectives2018
Comprehensive Analyses and Prioritization of Tox21 10K Chemicals Affecting Mitochondrial Function by in-Depth Mechanistic Studies.
Article in Environmental health perspectives, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
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- Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation.Archives of toxicology · 2022Article
- Mitochondrial Membrane Potential Assay.Methods in molecular biology (Clifton, N.J.) · 2022Article
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- Mild pentachlorophenol-mediated uncoupling of mitochondria depletes ATP but does not cause an oxidized redox state or dopaminergic neurodegeneration inCurrent research in toxicology · 2022Article
- Towards a reporting guideline for developmental and reproductive toxicology testing inToxicology research · 2021Article
- AOP Report: Uncoupling of Oxidative Phosphorylation Leading to Growth Inhibition via Decreased Cell Proliferation.Environmental toxicology and chemistry · 2021Article
- MitoTox: a comprehensive mitochondrial toxicity database.BMC bioinformatics · 2021Article
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Corrections and comments
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Authors and funding
24 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundA central challenge in toxicity testing is the large number of chemicals in commerce that lack toxicological assessment. In response, the Tox21 program is re-focusing toxicity testing from animal studies to less expensive and higher throughput
objectivesOur objective was to use an in-depth mechanistic study approach to prioritize and characterize the chemicals affecting mitochondrial function.
methodsWe used a tiered testing approach to prioritize for more extensive testing 622 compounds identified from a primary, quantitative high-throughput screen of 8,300 unique small molecules, including drugs and industrial chemicals, as potential mitochondrial toxicants by their ability to significantly decrease the mitochondrial membrane potential (MMP). Based on results from secondary MMP assays in HepG2 cells and rat hepatocytes, 34 compounds were selected for testing in tertiary assays that included formation of reactive oxygen species (ROS), upregulation of p53 and nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), mitochondrial oxygen consumption, cellular Parkin translocation, and larval development and ATP status in the nematode
resultsA group of known mitochondrial complex inhibitors (e.g., rotenone) and uncouplers (e.g., chlorfenapyr), as well as potential novel complex inhibitors and uncouplers, were detected. From this study, we identified four not well-characterized potential mitochondrial toxicants (lasalocid, picoxystrobin, pinacyanol, and triclocarban) that merit additional
conclusionsThe tier-based approach for identifying and mechanistically characterizing mitochondrial toxicants can potentially reduce animal use in toxicological testing. https://doi.org/10.1289/EHP2589.
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