Journal article
Use of a Polymeric Implant System to Assess the Neurotoxicity of Subacute Exposure to 2,2',5,5'-Tetrachlorobiphenyl-4-ol, a Human Metabolite of PCB 52, in Male Adolescent Rats
Toxicology (Amsterdam), Vol.500, 153677
12/2023
DOI: 10.1016/j.tox.2023.153677
PMCID: PMC10757425
PMID: 37995827
Abstract
Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that ubiquitously exist in the environment. PCB exposure has been linked to cancer and multi-system toxicity, including endocrine disruption, immune inhibition, and reproductive and neurotoxicity. 2,2',5,5'-Tetrachloro-biphenyl (PCB 52) is one of the most frequently detected congeners in the environment and human blood. The hydroxylated metabolites of PCB 52 may also be neurotoxic, especially for children whose brains are still developing. However, it is challenging to discern the contribution of these metabolites to PCB neurotoxicity because the metabolism of PCB is species-dependent. In this study, we evaluated the subacute neurotoxicity of a human-relevant metabolite, 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-52), on male adolescent Sprague Dawley rats, via a novel polymeric implant drug delivery system grafted subcutaneously, at total loading concentrations ranging from 0%, 1%, 5%, and 10% of the implant (w/w) for 28 days. Y-maze, hole board test, open field test, and elevated plus maze were performed on exposure days 24 to 28 to assess their locomotor activity, and exploratory and anxiety-like behavior. 4-52 and other possible hydroxylated metabolites in serum and vital tissues were quantified using gas chromatography with tandem mass spectrometry (GC-MS/MS). Our results demonstrate the sustained release of 4-52 from the polymeric implants into the systemic circulation in serum and tissues. Dihydroxylated and dechlorinated metabolites were detected in serum and tissues, depending on the dose and tissue type. No statistically significant changes were observed in the neurobehavioral tasks across all exposure groups. The results demonstrate that subcutaneous polymeric implants provide a straightforward method to expose rats to phenolic PCB metabolites to study neurotoxic outcomes, e.g., in memory, anxiety, and exploratory behaviors.
Details
- Title: Subtitle
- Use of a Polymeric Implant System to Assess the Neurotoxicity of Subacute Exposure to 2,2',5,5'-Tetrachlorobiphenyl-4-ol, a Human Metabolite of PCB 52, in Male Adolescent Rats
- Creators
- Hui Wang - University of IowaAmanda J Bullert - University of IowaXueshu Li - University of IowaHanna Stevens - University of IowaAloysius J Klingelhutz - University of IowaJames A Ankrum - University of IowaAndrea Adamcakova-DoddPeter S Thorne - University of IowaHans-Joachim Lehmler
- Resource Type
- Journal article
- Publication Details
- Toxicology (Amsterdam), Vol.500, 153677
- DOI
- 10.1016/j.tox.2023.153677
- PMID
- 37995827
- PMCID
- PMC10757425
- NLM abbreviation
- Toxicology
- eISSN
- 1879-3185
- Language
- English
- Electronic publication date
- 11/21/2023
- Date published
- 12/2023
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Psychiatry; Civil and Environmental Engineering; Microbiology and Immunology; Occupational and Environmental Health; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Iowa Superfund Research Program
- Record Identifier
- 9984516958502771
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