Evidence map›Paper›PMID 25448357›Full record

ArticleExperimental parasitology2014

Piperaquine and Lumefantrine resistance in Plasmodium berghei ANKA associated with increased expression of Ca2+/H+ antiporter and glutathione associated enzymes.

Daniel Kiboi, Beatrice Irungu, Jennifer Orwa, Luna Kamau, Lynette Isabella Ochola-Oyier, Joseph Ngángá, Alexis Nzila

Abstract read
In one paragraph

Article in Experimental parasitology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Deletion of theAntimicrobial agents and chemotherapy · 2025
    Article
  3. Antimalarial Activity ofJournal of pathogens · 2021
    Article
  4. Amodiaquine resistance inWellcome open research · 2017
    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 3 institutions in 2 countries.

Daniel KiboiDepartment of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000-00200, Nairobi, Kenya; KEMRI-Centre for Traditional Medicine and Drug Research, P.O. Box 54840-00200, Nairobi, Kenya. Electronic address: muthuikiboi@gmail.com.
Beatrice IrunguKEMRI-Centre for Traditional Medicine and Drug Research, P.O. Box 54840-00200, Nairobi, Kenya.
Jennifer OrwaKEMRI-Centre for Traditional Medicine and Drug Research, P.O. Box 54840-00200, Nairobi, Kenya.
Luna KamauKEMRI-Centre for Biotechnology Research and Development, P.O. Box 54840-00200, Nairobi, Kenya.
Lynette Isabella Ochola-OyierKEMRI-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya.
Joseph NgángáDepartment of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, P.O. Box 62000-00200, Nairobi, Kenya.
Alexis NzilaDepartment of Chemistry, King Fahd University of Petroleum and Minerals, P.O. Box 468, Dharan 31261, Saudi Arabia.
Kenya Medical Research Institute · KEJomo Kenyatta University of Agriculture and Technology · KEKing Fahd University of Petroleum and Minerals · SA

Funding

Wellcome Trust 092654
6 · The paper itself

Abstract

We investigated the mechanisms of resistance of two antimalarial drugs piperaquine (PQ) and lumefantrine (LM) using the rodent parasite Plasmodium berghei as a surrogate of the human parasite, Plasmodium falciparum. We analyzed the whole coding sequence of Plasmodium berghei chloroquine resistance transporter (Pbcrt) and Plasmodium berghei multidrug resistance gene 1(Pbmdr-1) for polymorphisms. These genes are associated with quinoline resistance in Plasmodium falciparum. No polymorphic changes were detected in the coding sequences of Pbcrt and Pbmdr1 or in the mRNA transcript levels of Pbmdr1. However, our data demonstrated that PQ and LM resistance is achieved by multiple mechanisms that include elevated mRNA transcript levels of V-type H(+) pumping pyrophosphatase (vp2), Ca(2+)/H(+) antiporter (vcx1), gamma glutamylcysteine synthetase (ggcs) and glutathione-S-transferase (gst) genes, mechanisms also known to contribute to chloroquine resistance in P. falciparum and rodent malaria parasites. The increase in ggcs and gst transcript levels was accompanied by high glutathione (GSH) levels and elevated activity of glutathione-S-transferase (GST) enzyme. Taken together, these results demonstrate that Pbcrt and Pbmdr1 are not associated with PQ and LM resistance in P. berghei ANKA, while vp2, vcx1, ggcs and gst may mediate resistance directly or modulate functional mutations in other unknown genes.

Indexed as

AnimalsAntimalarialsAntiportersCation Transport ProteinsCloning, MolecularDNA, ProtozoanDrug Resistance, MultipleEthanolaminesFluorenesGene Expression Regulation, EnzymologicGlutathioneGlutathione PeroxidaseGlutathione ReductaseGlutathione TransferaseLumefantrineMaleAntimalarialsAntiporterscalcium-hydrogen antiportersCation Transport ProteinsDNA, ProtozoanEthanolaminesFluorenesGlutathioneGlutathione PeroxidaseGlutathione ReductaseGlutathione TransferaseLumefantrinepiperaquinePiperazinesQuinolinesLumefantrineMalariaPiperaquinePlasmodium bergheiResistance

Identifiers

PMID25448357
PMCPMC6128398
OpenAlexW2001888038

What OpenQuestion holds

Textmetadata
LicenceTDM
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.