Evidence map›Paper›PMID 16925582›Full record

ArticleCancer science2006

Effect of methotrexate treatment on expression levels of multidrug resistance protein 2, breast cancer resistance protein and organic anion transporters Oat1, Oat2 and Oat3 in rats.

Yoshihiko Shibayama, Kazami Ushinohama, Ryuji Ikeda, Yoshimi Yoshikawa, Toshiro Motoya, Yasuo Takeda, Katsushi Yamada

Open access · greenAbstract read
In one paragraph

Article in Cancer science, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

12 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Regulation of P-Glycoprotein during Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024
    Review
  3. Drug metabolism and disposition: the biological fate of chemicals · 2022
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. What do drug transporters really do?Nature reviews. Drug discovery · 2015
    Review
  9. Increased susceptibility to methotrexate-induced toxicity in nonalcoholic steatohepatitis.Toxicological sciences : an official journal of the Society of Toxicology · 2014
    Article
  10. Article
  11. Article
  12. 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 2 institutions in 1 country.

Yoshihiko ShibayamaDepartment of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
Kazami Ushinohama
Ryuji Ikeda
Yoshimi Yoshikawa
Toshiro Motoya
Yasuo Takeda
Katsushi Yamada
Kagoshima University · JPKyushu University of Health and Welfare · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ATP binding cassette (ABC) transporters, multidrug resistance protein 2 (Mrp2; Abcc2) and breast cancer resistance protein (Bcrp; Abcg2), and organic anion transporters (Oats) mediate excretion of methotrexate (MTX) and many other drugs. However, it is not known whether MTX treatment leads to any changes in the expression of these transporters. We examined the effect of MTX treatment on expression of Mrp2, Bcrp and Oats in rats. MTX was single injected intraperitoneally at doses of 10, 50 and 150 mg/kg, and then Western blot analysis was performed. The levels of Mrp2, Oat1 and Oat2 on day 1 after the treatment showed no significant change. Four days after injection of 150 mg/kg MTX, the Mrp2 levels in the liver and ileum, but not in the kidney, were markedly down-regulated to 20 +/- 3.6% and 8.9 +/- 3.8% (mean +/- SEM) of controls, respectively. Renal Oat1 and Oat3 were also down-regulated to 56.4 +/- 4.3% (Oat1) and 54.3 +/- 5.5% (Oat3) of controls. These effects of MTX were almost recovered by leucovorin which rescues normal cells from MTX toxicity. MTX treatment also decreased mRNA levels of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) to 65.5 +/- 17.9% and 59.6 +/- 14.5% of controls in the liver, respectively. MTX treatment has no apparent effect on expression levels of Bcrp, cytochrome P450 2B6 and 3A1. In conclusion, these data indicate that MTX treatment down-regulates expression levels of Mrp2, Oat1 and Oat3, and its effects are recovered by leucovorin.

Indexed as

AnimalsAntimetabolites, AntineoplasticATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2Blotting, WesternDown-RegulationHeartLeucovorinMaleMethotrexateOrganic Anion Transporters, Sodium-IndependentOrganic Anion Transport Protein 1RatsRats, WistarReverse Transcriptase Polymerase Chain ReactionRNA, MessengerAbcc2 protein, ratAbcg2 protein, ratAntimetabolites, AntineoplasticATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2LeucovorinMethotrexateOrganic Anion Transporters, Sodium-IndependentOrganic Anion Transport Protein 1organic anion transport protein 3RNA, MessengerSlc22a6 protein, ratSlc22a7 protein, ratVitamin B Complex

Identifiers

PMID16925582
PMCPMC11159268
OpenAlexW1994633554

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.