Evidence map›Paper›PMID 29529285›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2018

Disruption of Nuclear Receptor Signaling Alters Triphenyl Phosphate-Induced Cardiotoxicity in Zebrafish Embryos.

Constance A Mitchell, Subham Dasgupta, Sharon Zhang, Heather M Stapleton, David C Volz

Open access · bronzeAbstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 7% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Constance A MitchellEnvironmental Toxicology Graduate Program.
Subham DasguptaDepartment of Environmental Sciences, University of California, Riverside, California.
Sharon ZhangDivision of Environmental Sciences and Policy, Duke University, Durham, North Carolina.
Heather M StapletonDivision of Environmental Sciences and Policy, Duke University, Durham, North Carolina.
David C VolzDepartment of Environmental Sciences, University of California, Riverside, California.
University of California, Riverside · USDuke University · US

Funding

DEVELOPMENTAL TOXICITY OF ORGANOPHOSPHATE-BASED FLAME RETARDANTSR01ES027576 · NIEHS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI VOLZ, DAVID C. · 2017 to 2021
$1.9M
DEVELOPMENTAL TOXICITY OF ORGANOPHOSPHATE-BASED FLAME RETARDANTSR21ES022797 · NIEHS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI VOLZ, DAVID C. · 2014 to 2015
$418k
NIEHS NIH HHS R01 ES027576NIEHS NIH HHS R21 ES022797
6 · The paper itself

Abstract

Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on (1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and (2) high-content screening to identify nuclear receptor ligands that enhance or mitigate TPHP-induced cardiotoxicity. Based on mRNA-sequencing, TPHP exposure from 24 to 72-h postfertilization (hpf) resulted in a concentration-dependent increase in the number of transcripts significantly affected at 72 hpf, and pathway analysis revealed that 5 out of 9 nuclear receptor pathways were associated with the retinoid X receptor (RXR). Based on a screen of 74 unique nuclear receptor ligands as well as follow-up experiments, 2 compounds-ciglitazone (a peroxisome proliferator-activated receptor gamma, or PPARγ, agonist) and fenretinide (a pan-retinoic acid receptor, or RAR, agonist)-reliably mitigated TPHP-induced cardiotoxicity in the absence of effects on TPHP uptake or metabolism. As these data suggested that TPHP may be activating RXR (a heterodimer for both RARs and PPARγ), we coexposed embryos to HX 531-a pan-RXR antagonist-from 24 to 72 hpf and, contrary to our hypothesis, found that coexposure to HX 531 significantly enhanced TPHP-induced cardiotoxicity. Using a luciferase reporter assay, we also found that TPHP did not activate nor inhibit chimeric human RXRα, RXRβ, or RXRγ, suggesting that TPHP does not directly bind nor interact with RXRs. Overall, our data suggest that TPHP may interfere with RXR-dependent pathways involved in cardiac development.

Indexed as

AnimalsCardiotoxicityDose-Response Relationship, DrugEmbryo, NonmammalianFlame RetardantsOrganogenesisOrganophosphatesPericardiumPPAR gammaReceptors, Retinoic AcidRetinoid X ReceptorsSignal TransductionZebrafishFlame RetardantsOrganophosphatesPPAR gammaReceptors, Retinoic AcidRetinoid X Receptorstriphenyl phosphate

Identifiers

PMID29529285
PMCPMC5920347
OpenAlexW2789642372

What OpenQuestion holds

Textmetadata
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.