Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure

Amanda Bullert; Xueshu Li; Chunyun Zhang; Kendra Lee; Brianna S Cagle; Jonathan A Doorn; Aloysius J Klingelhutz; Larry W Robertson; Hans-Joachim Lehmler

doi:10.1101/2023.06.19.544952

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Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure

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Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure

Amanda Bullert, Xueshu Li, Chunyun Zhang, Kendra Lee, Brianna S Cagle, Jonathan A Doorn, Aloysius J Klingelhutz, Larry W Robertson and Hans-Joachim Lehmler

bioRxiv : the preprint server for biology

08/09/2023

DOI: 10.1101/2023.06.19.544952

PMCID: PMC10441371

PMID: 37609242

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https://doi.org/10.1101/2023.06.19.544952View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

The disposition and toxicity of lower chlorinated PCBs (LC-PCBs) with less than five chlorine substituents have received little attention. This study characterizes the distribution and metabolomic effects of PCB 52, an LC-PCB found in indoor and outdoor air, three weeks after intraperitoneal exposure of female Sprague Dawley rats to 0, 1, 10, or 100 mg/kg BW. PCB 52 exposure did not affect overall body weight. Gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis identified PCB 52 in all tissues investigated. Hydroxylated, sulfated, and methylated PCB metabolites, identified using GC-MS/MS and nontarget liquid chromatography-high resolution mass spectrometry (Nt-LCMS), were primarily found in the serum and liver of rats exposed to 100 mg/kg BW. Metabolomic analysis revealed minor effects on L-cysteine, glycine, cytosine, sphingosine, thymine, linoleic acid, orotic acid, L-histidine, and erythrose serum levels. Thus, the metabolism of PCB 52 and its effects on the metabolome must be considered in toxicity studies. HighlightsPCB 52 was present in adipose, brain, liver, and serum 3 weeks after PCB exposureLiver and serum contained hydroxylated, sulfated, and methylated PCB 52 metabolitesMetabolomics analysis revealed minor changes in endogenous serum metabolitesLevels of dopamine and its metabolites in the brain were not affected by PCB 52.

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Title: Subtitle: Disposition and Metabolomic Effects of 2,2',5,5'-Tetrachlorobiphenyl in Female Rats Following Intraperitoneal Exposure
Creators: Amanda Bullert - University of Iowa
Xueshu Li
Chunyun Zhang
Kendra Lee
Brianna S Cagle
Jonathan A Doorn
Aloysius J Klingelhutz - University of Iowa
Larry W Robertson - University of Iowa
Hans-Joachim Lehmler - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv : the preprint server for biology
DOI: 10.1101/2023.06.19.544952
PMID: 37609242
PMCID: PMC10441371
Language: English
Date posted: 08/09/2023
Academic Unit: Microbiology and Immunology; Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Medicinal and Natural Products Chemistry
Record Identifier: 9984460454302771

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