Evidence map›Paper›PMID 21106720›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2011

Decreased hepatic breast cancer resistance protein expression and function in multidrug resistance-associated protein 2-deficient (TR⁻) rats.

Wei Yue, Jin Kyung Lee, Koji Abe, Yuichi Sugiyama, Kim L R Brouwer

Open access · bronzeAbstract read
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 17% 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, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. A perspective on efflux transport proteins in the liver.Clinical pharmacology and therapeutics · 2012
    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 1 institution in 1 country.

Wei YueDivision of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jin Kyung Lee
Koji Abe
Yuichi Sugiyama
Kim L R Brouwer
University of North Carolina at Chapel Hill · US

Funding

ALTERED HEPATIC DISPOSITION OF ANIONIC DRUGS-MECHANISMSR01GM041935 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BROUWER, KIM L.R. · 1997 to 2016
$6.5M
ALTERED HEPATIC DISPOSITION OF ANIONIC DRUGS-MECHANISMSR56GM041935 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BROUWER, KIM L.R. · 2009 to 2009
$365k
ALTERED HEPATIC DISPOSITION OF ANIONIC DRUGS: MECHANISMR29GM041935 · NIGMS · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI BROUWER, KIM L · 1991 to 1995
–
NIGMS NIH HHS GM41935NIGMS NIH HHS R01 GM041935NIGMS NIH HHS R56 GM041935
6 · The paper itself

Abstract

Multidrug resistance-associated protein (Mrp) 2-deficient (TR(-)) Wistar rats have been used to elucidate the role of Mrp2 in drug disposition. Decreased breast cancer resistance protein (Bcrp) levels were reported in sandwich-cultured hepatocytes (SCH) from TR(-) rats compared with those from wild-type (WT) rats. This study was designed to characterize hepatic Bcrp expression and function in TR(-) rats, using nitrofurantoin and pitavastatin as substrates. Bcrp was knocked down by RNA interference in rat SCH. Antibody BXP53, but not BXP21, specifically detected Bcrp knockdown in SCH. Bcrp protein levels were decreased markedly in TR(-) but not Mrp2-deficient Sprague-Dawley [Eisai hyperbilirubinemic rats (EHBR)] rats. Bcrp mRNA levels were decreased significantly in TR(-) livers as determined by TaqMan real-time reverse transcriptase-polymerase chain reaction. Biliary excretion of nitrofurantoin, a specific Bcrp substrate, was decreased significantly in SCH and isolated perfused livers from TR(-) rats compared with those from WT controls, indicating that hepatic Bcrp function is decreased in TR(-) rats. In Bcrp knockdown SCH, the biliary excretion index and in vitro biliary clearance of pitavastatin were decreased significantly to ∼ 58 and ∼ 52% of control, respectively, indicating that Bcrp plays a role in pitavastatin biliary excretion. Pitavastatin biliary excretion was decreased significantly in perfused livers from TR(-) compared with those from WT rats. In conclusion, expression and function of hepatic Bcrp are decreased significantly in TR(-) rats. The potential role of both Bcrp and Mrp2 should be considered when data generated in TR(-) rats are interpreted. TR(-) and EHBR rats in combination may be useful in differentiating the role of Mrp2 and Bcrp in drug/metabolite disposition.

Indexed as

Gene Expression RegulationAnimalsAnimals, Genetically ModifiedAnti-Bacterial AgentsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2BileBiliary TractBiological TransportCells, CulturedHydroxymethylglutaryl-CoA Reductase InhibitorsHyperbilirubinemiaIn Vitro TechniquesLiverMaleMetabolic Clearance RateAbcc2 protein, ratAbcg2 protein, ratAnti-Bacterial AgentsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2Hydroxymethylglutaryl-CoA Reductase InhibitorsNitrofurantoinpitavastatinQuinolinesRNA, MessengerRNA, Small Interfering

Identifiers

PMID21106720
PMCPMC3061562
OpenAlexW2119373527

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.