Evidence map›Paper›PMID 29884652›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2018

Consequences of Phenytoin Exposure on Hepatic Cytochrome P450 Expression during Postnatal Liver Maturation in Mice.

Stephanie C Piekos, Liming Chen, Pengcheng Wang, Jian Shi, Sharon Yaqoob, Hao-Jie Zhu, Xiaochao Ma, Xiao-Bo Zhong

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2018. 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
1.4field-weighted citation impact, top 20% 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, 8 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

8 authors at 3 institutions in 1 country.

Stephanie C PiekosDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.).
Liming ChenDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.).
Pengcheng WangDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.).
Jian ShiDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.).
Sharon YaqoobDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.).
Hao-Jie ZhuDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.).
Xiaochao MaDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.).
Xiao-Bo ZhongDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (S.C.P., L.C., S.Y., X.-b.Z.); Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania (P.W., X.M.); and Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, Michigan (J.S., H.-J.Z.) xiaobo.zhong@uconn.edu.
University of Connecticut · USUniversity of Michigan–Ann Arbor · USUniversity of Pittsburgh · US

Funding

Genetic determinants of ACEI prodrug activationR01HL126969 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHU, HAOJIE · 2016 to 2020
$1.9M
Mechanisms of adverse effects of anti-tuberculosis drugsR01DK090305 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MA, XIAOCHAO · 2012 to 2016
$1.6M
Short- or long-term impacts of drug exposure at early life on drug metabolism, therapeutic efficacy, and drug-induced toxicityR01GM118367 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI ZHONG, XIAO-BO · 2016 to 2019
$1.2M
NHLBI NIH HHS R01 HL126969NIDDK NIH HHS R01 DK090305NIGMS NIH HHS R01 GM118367
6 · The paper itself

Abstract

The induction of cytochrome P450 (P450) enzymes in response to drug treatment is a significant contributing factor to drug-drug interactions, which may reduce therapeutic efficacy and/or cause toxicity. Since most studies on P450 induction are performed in adults, enzyme induction at neonatal, infant, and adolescent ages is not well understood. Previous work defined the postnatal ontogeny of drug-metabolizing P450s in human and mouse livers; however, there are limited data on the ontogeny of the induction potential of each enzyme in response to drug treatment. Induction of P450s at the neonatal age may also cause permanent alterations in P450 expression in adults. The goal of this study was to investigate the short- and long-term effects of phenytoin treatment on mRNA and protein expressions and enzyme activities of CYP2B10, 2C29, 3A11, and 3A16 at different ages during postnatal liver maturation in mice. Induction of mRNA immediately following phenytoin treatment appeared to depend on basal expression of the enzyme at a specific age. While neonatal mice showed the greatest fold changes in CYP2B10, 2C29, and 3A11 mRNA expression following treatment, the levels of induced protein expression and enzymatic activity were much lower than that of induced levels in adults. The expression of fetal CYP3A16 was repressed by phenytoin treatment. Neonatal treatment with phenytoin did not permanently induce enzyme expression in adulthood. Taken together, our data suggest that inducibility of drug-metabolizing P450s is much lower in neonatal mice than it is in adults and neonatal induction by phenytoin is not permanent.

Indexed as

AnimalsCytochrome P-450 Enzyme SystemEnzyme InductionFemaleGene Expression Regulation, EnzymologicLiverMaleMiceMice, Inbred C57BLPhenytoinRNA, MessengerCytochrome P-450 Enzyme SystemPhenytoinRNA, Messenger

Identifiers

PMID29884652
PMCPMC6053591
OpenAlexW2805658817

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.