Evidence map›Paper›PMID 25418377›Full record

ArticleActa pharmacologica Sinica2014

Roles of P-glycoprotein and multidrug resistance protein in transporting para-aminosalicylic acid and its N-acetylated metabolite in mice brain.

Lan Hong, Cong Xu, Stefanie O'Neal, Hui-chang Bi, Min Huang, Wei Zheng, Su Zeng

Open access · bronzeAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2014. 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
1.2field-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

9 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017
    Review
  6. Article
  7. Evaluation ofAntimicrobial agents and chemotherapy · 2017
    Article
  8. Article
  9. Manganese Toxicity Upon Overexposure: a Decade in Review.Current environmental health reports · 2015
    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

7 authors at 3 institutions in 2 countries.

Lan Hong1] College of Pharmaceutical Sciences, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Zhejiang University, Hangzhou 310058, China [2] School of Health Sciences, Purdue University, West Lafayette, Indiana, USA.
Cong XuCollege of Pharmaceutical Sciences, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Zhejiang University, Hangzhou 310058, China.
Stefanie O'NealSchool of Health Sciences, Purdue University, West Lafayette, Indiana, USA.
Hui-chang BiInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Min HuangInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Wei ZhengSchool of Health Sciences, Purdue University, West Lafayette, Indiana, USA.
Su ZengCollege of Pharmaceutical Sciences, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Zhejiang University, Hangzhou 310058, China.
Zhejiang University · CNPurdue University West Lafayette · USSun Yat-sen University · CN

Funding

Choroid Plexus a Target in Metal-Induced NeurotoxicityR01ES008146 · NIEHS · PURDUE UNIVERSITY WEST LAFAYETTE · PI ZHENG, WEI · 1998 to 2014
$5.0M
NIEHS NIH HHS R01 ES008146
6 · The paper itself

Abstract

aimPara-aminosalicylic acid (PAS) is effective in the treatment of manganism-induced neurotoxicity (manganism). In this study we investigated the roles of P-glycoprotein (MDR1a) and multidrug resistance protein (MRP) in transporting PAS and its N-acetylated metabolite AcPAS through blood-brain barrier.

methodsMDR1a-null or wild-type mice were intravenously injected with PAS (200 mg/kg). Thirty minutes after the injection, blood samples and brains were collected, and the concentrations of PAS and AcPAS in brain capillaries and parenchyma were measured using HPLC. Both MDCK-MDR1 and MDCK-MRP1 cells that overexpressed P-gp and MRP1, respectively, were used in two-chamber Transwell transport studies in vitro.

resultsAfter injection of PAS, the brain concentration of PAS was substantially higher in MDR1a-null mice than in wild-type mice, but the brain concentration of AcPAS had no significant difference between MDR1a-null mice and wild-type mice. Concomitant injection of PAS with the MRP-specific inhibitor MK-571 (50 mg/kg) further increased the brain concentration of PAS in MDR1a-null mice, and increased the brain concentration of AcPAS in both MDR1a-null mice and wild-type mice. Two-chamber Transwell studies with MDCK-MDR1 cells demonstrated that PAS was not only a substrate but also a competitive inhibitor of P-gp, while AcPAS was not a substrate of P-gp. Two-chamber Transwell studies with the MDCK-MRP1 cells showed that MRP1 had the ability to transport both PAS and AcPAS across the BBB.

conclusionP-gp plays a major role in the efflux of PAS from brain parenchyma into blood in mice, while MRP1 is involved in both PAS and AcPAS transport in the brain.

Indexed as

AcetylationAminosalicylic AcidAminosalicylic AcidsAnimalsATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1BiotransformationBlood-Brain BarrierBrainCapillary PermeabilityDogsInjections, IntravenousMadin Darby Canine Kidney CellsMaleMembrane Transport Modulatorsacetyl 4-aminosalicylic acidAminosalicylic AcidAminosalicylic AcidsATP-Binding Cassette, Sub-Family C ProteinsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Membrane Transport Modulatorsmultidrug resistance-associated protein 1multidrug resistance protein 3

Identifiers

PMID25418377
PMCPMC4261121
OpenAlexW2168631592

What OpenQuestion holds

Textmetadata
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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.