Evidence map›Paper›PMID 27138278›Full record

ArticlePloS one2016

Skatole (3-Methylindole) Is a Partial Aryl Hydrocarbon Receptor Agonist and Induces CYP1A1/2 and CYP1B1 Expression in Primary Human Hepatocytes.

Martin Krøyer Rasmussen, Patrick Balaguer, Bo Ekstrand, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

39 citing papers in PubMed, 63 citations in OpenAlex.

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  16. Review
  17. Effects of Crocodile Oil (Veterinary medicine international · 2022
    Article
  18. Diverse roles of microbial indole compounds in eukaryotic systems.Biological reviews of the Cambridge Philosophical Society · 2021
    Review
  19. Article
  20. Review
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 3 institutions in 2 countries.

Martin Krøyer RasmussenINSERM, U1183, Institute of Regenerative Medicine and Biotherapy, Montpellier, F-34290, France.ORCID 0000-0002-1889-2874
Patrick BalaguerInstitut de Recherche en Cancérologie de Montpellier, Montpellier, F-34298, France.
Bo EkstrandDepartment of Food Science, Aarhus University, Foulum, Denmark.
Martine Daujat-ChavanieuINSERM, U1183, Institute of Regenerative Medicine and Biotherapy, Montpellier, F-34290, France.
Sabine Gerbal-ChaloinINSERM, U1183, Institute of Regenerative Medicine and Biotherapy, Montpellier, F-34290, France.
Inserm · FRAarhus University · DKInstitut de Recherche en Cancérologie de Montpellier · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Skatole (3-methylindole) is a product of bacterial fermentation of tryptophan in the intestine. A significant amount of skatole can also be inhaled during cigarette smoking. Skatole is a pulmonary toxin that induces the expression of aryl hydrocarbon receptor (AhR) regulated genes, such as cytochrome P450 1A1 (CYP1A1), in human bronchial cells. The liver has a high metabolic capacity for skatole and is the first organ encountered by the absorbed skatole; however, the effect of skatole in the liver is unknown. Therefore, we investigated the impact of skatole on hepatic AhR activity and AhR-regulated gene expression. Using reporter gene assays, we showed that skatole activates AhR and that this is accompanied by an increase of CYP1A1, CYP1A2 and CYP1B1 expression in HepG2-C3 and primary human hepatocytes. Specific AhR antagonists and siRNA-mediated AhR silencing demonstrated that skatole-induced CYP1A1 expression is dependent on AhR activation. The effect of skatole was reduced by blocking intrinsic cytochrome P450 activity and indole-3-carbinole, a known skatole metabolite, was a more potent inducer than skatole. Finally, skatole could reduce TCDD-induced CYP1A1 expression, suggesting that skatole is a partial AhR agonist. In conclusion, our findings suggest that skatole and its metabolites affect liver homeostasis by modulating the AhR pathway.

Indexed as

Drug Partial AgonismAdultAgedCytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2Cytochrome P-450 CYP1B1Cytochrome P450 Family 1FemaleGene Expression Regulation, EnzymologicGenes, ReporterHepatocytesHep G2 CellsHumansMaleMiddle AgedReceptors, Aryl HydrocarbonCYP1A2 protein, humanCYP1B1 protein, humanCytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2Cytochrome P-450 CYP1B1Cytochrome P450 Family 1Receptors, Aryl HydrocarbonSkatole

Identifiers

PMID27138278
PMCPMC4854444
OpenAlexW2347076396

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.