Evidence map›Paper›PMID 34045606›Full record

ArticleScientific reports2021

Potential of therapeutic bile acids in the treatment of neonatal Hyperbilirubinemia.

Lori W E van der Schoor, Henkjan J Verkade, Anna Bertolini, Sanne de Wit, Elvira Mennillo, Eva Rettenmeier, André A Weber, Rick Havinga, Petra Valášková, Jana Jašprová and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 5% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
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  7. Review
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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

17 authors at 3 institutions in 3 countries.

Lori W E van der SchoorSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Henkjan J VerkadeSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-7034-2861
Anna BertoliniSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Sanne de WitSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Elvira MennilloLaboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA.
Eva RettenmeierLaboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA.
André A WeberLaboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA.
Rick HavingaSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Petra ValáškováFourth Department of Internal Medicine and Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Jana JašprováFourth Department of Internal Medicine and Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Dicky StruikSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Vincent W BloksSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Shujuan ChenLaboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA.
Andrea B SchreuderSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Libor VítekFourth Department of Internal Medicine and Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University, Prague, Czech Republic.ORCID http://orcid.org/0000-0002-5318-0151
Robert H TukeyLaboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, CA, 92093, USA. rtukey@ucsd.edu.
Johan W JonkerSection of Molecular Metabolism and Nutrition, Laboratory of Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. j.w.jonker@umcg.nl.
University Medical Center Groningen · NLUniversity of California San Diego · USCharles University · CZ

Funding

Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
Xenobiotic sensors PXR and CAR and regulation of the UGT1 locusR01GM086713 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2009 to 2017
$2.6M
Novel regulatory events that control expression of the UGT1A1 geneR01GM126074 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2018 to 2021
$1.2M
NIEHS NIH HHS P42 ES010337NIGMS NIH HHS R01 GM086713NIGMS NIH HHS R01 GM126074U.S. Department of Health and Human Services (U.S. Department of Health & Human Services) ES010337U.S. Department of Health and Human Services (U.S. Department of Health & Human Services) GM086713U.S. Department of Health and Human Services (U.S. Department of Health & Human Services) GM126074
6 · The paper itself

Abstract

Neonatal hyperbilirubinemia or jaundice is associated with kernicterus, resulting in permanent neurological damage or even death. Conventional phototherapy does not prevent hyperbilirubinemia or eliminate the need for exchange transfusion. Here we investigated the potential of therapeutic bile acids ursodeoxycholic acid (UDCA) and obeticholic acid (OCA, 6-α-ethyl-CDCA), a farnesoid-X-receptor (FXR) agonist, as preventive treatment options for neonatal hyperbilirubinemia using the hUGT1*1 humanized mice and Ugt1a-deficient Gunn rats. Treatment of hUGT1*1 mice with UDCA or OCA at postnatal days 10-14 effectively decreased bilirubin in plasma (by 82% and 62%) and brain (by 72% and 69%), respectively. Mechanistically, our findings indicate that these effects are mediated through induction of protein levels of hUGT1A1 in the intestine, but not in liver. We further demonstrate that in Ugt1a-deficient Gunn rats, UDCA but not OCA significantly decreases plasma bilirubin, indicating that at least some of the hypobilirubinemic effects of UDCA are independent of UGT1A1. Finally, using the synthetic, non-bile acid, FXR-agonist GW4064, we show that some of these effects are mediated through direct or indirect activation of FXR. Together, our study shows that therapeutic bile acids UDCA and OCA effectively reduce both plasma and brain bilirubin, highlighting their potential in the treatment of neonatal hyperbilirubinemia.

Indexed as

AnimalsBile Acids and SaltsBilirubinChenodeoxycholic AcidHyperbilirubinemia, NeonatalIleumIsoxazolesLiverMiceRatsRats, GunnReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearTreatment OutcomeUrsodeoxycholic AcidBile Acids and SaltsBilirubinChenodeoxycholic AcidGW 4064Isoxazolesobeticholic acidReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearUrsodeoxycholic Acid

Identifiers

PMID34045606
PMCPMC8160219
OpenAlexW3164657912

What OpenQuestion holds

Textmetadata
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.