Evidence map›Paper›PMID 25409894›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2015

Characterization of CYP2B6 in a CYP2B6-humanized mouse model: inducibility in the liver by phenobarbital and dexamethasone and role in nicotine metabolism in vivo.

Zhihua Liu, Lei Li, Hong Wu, Jing Hu, Jun Ma, Qing-Yu Zhang, Xinxin Ding

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.4field-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

7 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. 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

7 authors at 4 institutions in 1 country.

Zhihua LiuWadsworth Center, New York State Department of Health, and School of Public Health, University at Albany, Albany, New York (Z.L., L.L., H.W., J.H., J.M., Q.-Y.Z., X.D.); and College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York (X.D.).
Lei LiWadsworth Center, New York State Department of Health, and School of Public Health, University at Albany, Albany, New York (Z.L., L.L., H.W., J.H., J.M., Q.-Y.Z., X.D.); and College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York (X.D.).
Hong WuWadsworth Center, New York State Department of Health, and School of Public Health, University at Albany, Albany, New York (Z.L., L.L., H.W., J.H., J.M., Q.-Y.Z., X.D.); and College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York (X.D.).
Jing HuWadsworth Center, New York State Department of Health, and School of Public Health, University at Albany, Albany, New York (Z.L., L.L., H.W., J.H., J.M., Q.-Y.Z., X.D.); and College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York (X.D.).
Jun MaWadsworth Center, New York State Department of Health, and School of Public Health, University at Albany, Albany, New York (Z.L., L.L., H.W., J.H., J.M., Q.-Y.Z., X.D.); and College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York (X.D.).
Qing-Yu ZhangWadsworth Center, New York State Department of Health, and School of Public Health, University at Albany, Albany, New York (Z.L., L.L., H.W., J.H., J.M., Q.-Y.Z., X.D.); and College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York (X.D.).
Xinxin DingWadsworth Center, New York State Department of Health, and School of Public Health, University at Albany, Albany, New York (Z.L., L.L., H.W., J.H., J.M., Q.-Y.Z., X.D.); and College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York (X.D.) xding@sunycnse.com.
SUNY Polytechnic Institute · USUniversity at Albany, State University of New York · USWadsworth Center · USNew York State Department of Health · US

Funding

Metabolic Mechanisms of Naphthalene Toxicity in LungR01ES020867 · NIEHS · WADSWORTH CENTER · PI Xinxin Ding, Laura S Van Winkle · 2013 to 2026
$6.4M
Human CYP2A and respiratory tract xenobiotic toxicityR01CA092596 · NCI · WADSWORTH CENTER · PI DING, XINXIN · 2003 to 2020
$6.1M
NCI NIH HHS CA092596NCI NIH HHS R01 CA092596NIEHS NIH HHS ES020867NIEHS NIH HHS R01 ES020867
6 · The paper itself

Abstract

The aim of this study was to further characterize the expression and function of human CYP2B6 in a recently generated CYP2A13/2B6/2F1-transgenic (TG) mouse model, in which CYP2B6 is expressed selectively in the liver. The inducibility of CYP2B6 by phenobarbital (PB) and dexamethasone (DEX), known inducers of CYP2B6 in human liver, was examined in the TG mice, as well as in TG/Cyp2abfgs-null (or "CYP2B6-humanized") mice. Hepatic expression of CYP2B6 mRNA and protein was greatly induced by PB or DEX treatment in both TG and TG/Cyp2abfgs-null mice. Function of the transgenic CYP2B6 was first studied using bupropion as a probe substrate. In PB-treated mice, the rates of hepatic microsomal hydroxybupropion formation (at 50 μM bupropion) were >4-fold higher in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice (for both male and female mice); the rate difference was accompanied by a 5-fold higher catalytic efficiency in the TG/Cyp2abfgs-null mice and was abolished by an antibody to CYP2B6. The ability of CYP2B6 to metabolize nicotine was then examined, both in vitro and in vivo. The rates of hepatic microsomal cotinine formation from nicotine were significantly higher in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice, pretreated with PB or DEX. Furthermore, systemic nicotine metabolism was faster in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice. Thus, the transgenic CYP2B6 was inducible and functional, and, in the absence of mouse CYP2A and CYP2B enzymes, it contributed to nicotine metabolism in vivo. The CYP2B6-humanized mouse will be valuable for studies on in vivo roles of hepatic CYP2B6 in xenobiotic metabolism and toxicity.

Indexed as

AnimalsAnti-Inflammatory AgentsAryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2B6Cytochrome P-450 CYP2B6 InducersCytochrome P-450 CYP2B6 InhibitorsCytochrome P-450 Enzyme SystemDexamethasoneEnzyme InductionFemaleHumansHypnotics and SedativesLiverMaleMice, Inbred C57BLMice, KnockoutAnti-Inflammatory AgentsAryl Hydrocarbon HydroxylasesCYP2B6 protein, humanCytochrome P-450 CYP2B6Cytochrome P-450 CYP2B6 InducersCytochrome P-450 CYP2B6 InhibitorsCytochrome P-450 Enzyme SystemDexamethasoneHypnotics and SedativesNicotinePhenobarbitalRecombinant Proteins

Identifiers

PMID25409894
PMCPMC4293397
OpenAlexW2136605181

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.