Journal article
Structure-Activity Relationship of Lower Chlorinated Biphenyls and Their Human-Relevant Metabolites for Astrocyte Toxicity
Chemical research in toxicology, Vol.36(6), pp.971-981
06/06/2023
DOI: 10.1021/acs.chemrestox.3c00095
PMCID: PMC10283044
PMID: 37279407
Appears in UI Libraries Support Open Access
Abstract
Exposure to polychlorinated biphenyls (PCBs) is associated with developmental neurotoxicity and neurodegenerative disorders; however, the underlying mechanisms of pathogenesis are unknown. Existing literature has focused mainly on using neurons as a model system to study mechanisms of PCB-mediated neurotoxicity, overlooking the role of glial cells, such as astrocytes. As normal brain function is largely astrocyte-dependent, we hypothesize that astrocytes play an important role in PCB-mediated injury to neurons. We assessed the toxicity of two commercial PCB mixtures, Aroclor 1016 and Aroclor 1254, and a non-Aroclor PCB mixture found in residential air called the Cabinet mixture, all of which contain lower chlorinated PCBs (LC-PCBs) found in indoor and outdoor air. We further assessed the toxicity of five abundant airborne LC-PCBs and their corresponding human-relevant metabolites in vitro models of astrocytes, namely, the C6 cell line and primary astrocytes isolated from Sprague–Dawley rats and C57BL/6 mice. PCB52 and its human-relevant hydroxylated and sulfated metabolites were found to be the most toxic compounds. No significant sex-dependent cell viability differences were observed in rat primary astrocytes. Based on the equilibrium partitioning model, it was predicted that the partitioning of LC-PCBs and their corresponding metabolites in biotic and abiotic compartments of the cell culture system is structure-dependent and that the observed toxicity is consistent with this prediction. This study, for the first time, shows that astrocytes are sensitive targets of LC-PCBs and their human-relevant metabolites and that further research to identify mechanistic targets of PCB exposure in glial cells is necessary.
Details
- Title: Subtitle
- Structure-Activity Relationship of Lower Chlorinated Biphenyls and Their Human-Relevant Metabolites for Astrocyte Toxicity
- Creators
- Neha Paranjape - University of IowaLaura E Dean - University of IowaAndres Martinez - University of IowaRonald B Tjalkens - Colorado State UniversityHans-Joachim Lehmler - University of IowaJonathan A Doorn - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.36(6), pp.971-981
- DOI
- 10.1021/acs.chemrestox.3c00095
- PMID
- 37279407
- PMCID
- PMC10283044
- NLM abbreviation
- Chem Res Toxicol
- eISSN
- 1520-5010
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100000066, name: National Institute of Environmental Health Sciences, award: P30 ES005605, P42 ES013661, R01 ES021656, R01 ES029035; DOI: 10.13039/100011291, name: American College of Toxicology; DOI: 10.13039/100008893, name: University of Iowa
- Language
- English
- Date published
- 06/06/2023
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; IIHR--Hydroscience and Engineering; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984426855402771
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