Evidence map›Paper›PMID 28725001›Full record

ArticleScientific reports2017

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.

Kelly A Fader, Rance Nault, Chen Zhang, Kazuyoshi Kumagai, Jack R Harkema, Timothy R Zacharewski

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.5field-weighted citation impact, top 6% of its field
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

40 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Cystine/Glutamate XcChemical research in toxicology · 2023
    Article
  11. Review
  12. Aryl hydrocarbon receptor activation affects nitrergic neuronal survival and delays intestinal motility in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023
    Article
  13. Article
  14. Single-cell transcriptomics shows dose-dependent disruption of hepatic zonation by TCDD in mice.Toxicological sciences : an official journal of the Society of Toxicology · 2023
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-International journal of molecular sciences · 2021
    Article
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

6 authors at 1 institution in 1 country.

Kelly A FaderDepartment of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Rance NaultDepartment of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA.
Chen ZhangDepartment of Chemistry, Michigan State University, East Lansing, MI, 48824, USA.ORCID 0000-0002-0839-3123
Kazuyoshi KumagaiDepartment of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, 48824, USA.
Jack R HarkemaInstitute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
Timothy R ZacharewskiDepartment of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA. tzachare@msu.edu.
Michigan State University · US

Funding

VOLATILE ORGANIC CONTAMINANTS--QUANTIFYING THEIR MOVEMENT IN THE UNSATURATED ZONEP42ES004911 · NIEHS · MICHIGAN STATE UNIVERSITY · PI Timothy R. Zacharewski · 1989 to 2026
$64.9M
Integrative Training in the Pharmacological SciencesT32GM092715 · NIGMS · MICHIGAN STATE UNIVERSITY · PI NEUBIG, RICHARD R · 2011 to 2020
$1.5M
CIHR DFS-140386NIEHS NIH HHS P42 ES004911NIGMS NIH HHS T32 GM092715
6 · The paper itself

Abstract

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30 µg/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1. Specifically, TCDD elicited a >200-fold increase in taurolithocholic acid (TLCA), a potent G protein-coupled bile acid receptor 1 (GPBAR1) agonist associated with bile duct proliferation. Increased levels of microbial bile acid metabolism loci (bsh, baiCD) are consistent with accumulation of TLCA and other secondary bile acids. Fecal bile acids decreased 2.8-fold, suggesting enhanced intestinal reabsorption due to induction of ileal transporters (Slc10a2, Slc51a) and increases in whole gut transit time and intestinal permeability. Moreover, serum bile acids were increased 45.4-fold, consistent with blood-to-hepatocyte transporter repression (Slco1a1, Slc10a1, Slco2b1, Slco1b2, Slco1a4) and hepatocyte-to-blood transporter induction (Abcc4, Abcc3). These results suggest that systemic alterations in enterohepatic circulation, as well as host and microbiota bile acid metabolism, favor bile acid accumulation that contributes to AhR-mediated hepatotoxicity.

Indexed as

AnimalsBacteriaBile Acids and SaltsCholesterolEnterohepatic CirculationFecesFemaleGenes, BacterialHomeostasisHydrophobic and Hydrophilic InteractionsIntestinal AbsorptionLiverMaleMice, Inbred C57BLPolychlorinated DibenzodioxinsBile Acids and SaltsCholesterolPolychlorinated Dibenzodioxins

Identifiers

PMID28725001
PMCPMC5517430
OpenAlexW2734877939

What OpenQuestion holds

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LicenceCC BY
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.