Evidence map›Paper›PMID 27413119›Full record

ArticleMolecular pharmacology2016

Induction of the UDP-Glucuronosyltransferase 1A1 during the Perinatal Period Can Cause Neurodevelopmental Toxicity.

Rika Hirashima, Hirofumi Michimae, Hiroaki Takemoto, Aya Sasaki, Yoshinori Kobayashi, Tomoo Itoh, Robert H Tukey, Ryoichi Fujiwara

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

Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
4.6field-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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. [Correlation between the mutation spectrum of the UGT1A1 gene and clinical phenotype in patients with inherited hyperunconjugated bilirubinemia].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024
    Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Efficacy and Safety of Bictegravir-Based Regimen in Pregnant Women Living with HIV: A Case Report.Journal of the International Association of Providers of AIDS Care
    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

8 authors at 2 institutions in 2 countries.

Rika HirashimaDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.).
Hirofumi MichimaeDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.).
Hiroaki TakemotoDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.).
Aya SasakiDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.).
Yoshinori KobayashiDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.).
Tomoo ItohDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.).
Robert H TukeyDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.).
Ryoichi FujiwaraDepartment of Pharmaceutics (R.H., A.S., T.I., R.F.), Division of Biostatistics (H.M.), and Department of Pharmacognosy (H.T., Y.K.), School of Pharmacy, Kitasato University, Tokyo, Japan; and Laboratory of Environmental Toxicology, Department of Pharmacology, University of California San Diego, La Jolla, California (R.H.T.) fujiwarar@pharm.kitasato-u.ac.jp.
Kitasato University · JPUniversity of California, San Diego · US

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
Neonatal hyperbilirubinemia in a humanized UGT1 animal modelR01GM100481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2012 to 2015
$1.3M
NIEHS NIH HHS P42 ES010337NIGMS NIH HHS R01 GM086713NIGMS NIH HHS R01 GM100481
6 · The paper itself

Abstract

Anticonvulsants can increase the risk of developing neurotoxicity in infants; however, the underlying mechanism has not been elucidated to date. Thyroxine [3,5,3',5'-l-tetraiodothyronine (T4)] plays crucial roles in the development of the central nervous system. In this study, we hypothesized that induction of UDP-glucuronosyltransferase 1A1 (UGT1A1)-an enzyme involved in the metabolism of T4-by anticonvulsants would reduce serum T4 levels and cause neurodevelopmental toxicity. Exposure of mice to phenytoin during both the prenatal and postnatal periods significantly induced UGT1A1 and decreased serum T4 levels on postnatal day 14. In the phenytoin-treated mice, the mRNA levels of synaptophysin and synapsin I in the hippocampus were lower than those in the control mice. The thickness of the external granule cell layer was greater in phenytoin-treated mice, indicating that induction of UGT1A1 during the perinatal period caused neurodevelopmental disorders. Exposure to phenytoin during only the postnatal period also caused these neurodevelopmental disorders. A T4 replacement attenuated the increase in thickness of the external granule cell layer, indicating that the reduced T4 was specifically associated with the phenytoin-induced neurodevelopmental disorder. In addition, these neurodevelopmental disorders were also found in the carbamazepine- and pregnenolone-16-α-carbonitrile-treated mice. Our study is the first to indicate that UGT1A1 can control neurodevelopment by regulating serum T4 levels.

Indexed as

AnimalsAnimals, NewbornBrainCarbamazepineCell MovementEnzyme InductionFemaleGene Expression Regulation, DevelopmentalGenes, DevelopmentalGlucuronosyltransferaseHumansMice, Inbred C57BLMice, TransgenicMilk, HumanNeurodevelopmental DisordersPhenytoinCarbamazepineGlucuronosyltransferasePhenytoinPregnenolone CarbonitrileRNA, MessengerThyroxineUGT1A1 Enzyme

Identifiers

PMID27413119
PMCPMC4998668
OpenAlexW2467891708

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.