Evidence map›Paper›PMID 40097135›Full record

ArticleToxicology2025

Subacute exposure of male adolescent rats to 2,2',5,5'-tetrachlorobiphenyl-4-ol via a polymeric implant causes gene expression changes in the brain and metabolomic disruption in serum.

Hui Wang, Amanda J Bullert, Morgan J Linahon, Michael E Dailey, Jonathan A Doorn, Aloysius J Klingelhutz, James A Ankrum, Hans-Joachim Lehmler

Abstract read
In one paragraph

Article in Toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Hui WangDepartment of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA.
Amanda J BullertDepartment of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA.
Morgan J LinahonDepartment of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA.
Michael E DaileyInterdisciplinary Graduate Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA; Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
Jonathan A DoornDepartment of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, IA 52242, USA.
Aloysius J KlingelhutzDepartment of Microbiology & Immunology, The University of Iowa, Iowa City, IA 52242, USA.
James A AnkrumRoy J. Carver Department of Biomedical Engineering, The University of Iowa, Iowa City, IA 52242, USA.
Hans-Joachim LehmlerDepartment of Occupational and Environmental Health, The University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Neuroscience, The University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, 52242, USA. Electronic address: hans-joachim-lehmler@uiowa.edu.

Funding

Training CoreP42ES013661 · NIEHS · UNIVERSITY OF IOWA · PI HANS-JOACHIM LEHMLER · 2006 to 2026
$60.3M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
NIEHS NIH HHS P30 ES005605NIEHS NIH HHS P42 ES013661
6 · The paper itself

Abstract

Polychlorinated biphenyls (PCBs) remain an environmental health concern due to their persistence and ongoing release from legacy and emerging sources. 2,2',5,5'-Tetrachlorobiphenyl (PCB52), a PCB congener frequently detected in the environment and human blood, is oxidized to 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-52). The neurotoxicity of this hydroxylated (OH-PCB) metabolite remains poorly characterized. In this study, we exposed 4-week-old male Sprague Dawley rats to 4-52 via a polymeric implant drug delivery system grafted in the subcutaneous cavity at 4-52 concentrations of 0 %, 1 %, 5 %, and 10 % in the implant (w/w) for 28 days. Metabolomic analyses were performed in the serum. RNA sequencing, immunofluorescence, and dopamine (DA) measurement with electrochemical detection were used to characterize the effects of 4-52 on the striatum and cerebellum, brain regions implicated in PCB neurotoxicity. Serum metabolomic analysis revealed disruptions in the "arginine biosynthesis" pathway following 4-52 exposure. Exposure to 4-52 caused moderate transcriptomic changes in pathways related to "oxidative phosphorylation" and "neuroactive ligand-receptor interactions." Immunofluorescence showed no significant alterations in microglial, astrocytic, or apoptotic biomarkers. In the medium dose group, the levels of the DA metabolite DOPAL (3,4-dihydroxyphenylacetaldehyde) were significantly reduced in the striatum. Subsequent multi-omics network analysis identified interactions among OH-PCBs, endogenous metabolites, and the transcriptome. For example, levels of glutamic acid, aspartic acid, choline, and glycerophosphocholine negatively correlated with 4-52 in the striatum. Expression levels of heat shock protein (HSP) family genes, Hsp90b1, Hspa8, and Hspa5, positively correlated with serum metabolites, including proline, 1-methylguanidine, and methionine sulfoxide. These findings identify novel biomarkers and targets of 4-52-induced neurotoxicity.

Indexed as

BrainEnvironmental PollutantsGene ExpressionPolychlorinated BiphenylsAnimalsDrug ImplantsMaleMetabolomicsPolymersRatsRats, Sprague-DawleyDrug ImplantsEnvironmental PollutantsPolychlorinated BiphenylsPolymersDopamineMetabolomicsNeurotoxicityPolychlorinated biphenylsPolymeric implantTranscriptomics

Identifiers

PMID40097135
PMCPMC11994288

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.