Evidence map›Paper›PMID 24586264›Full record

ArticlePloS one2014

Tempol, an intracellular antioxidant, inhibits tissue factor expression, attenuates dendritic cell function, and is partially protective in a murine model of cerebral malaria.

Ivo M B Francischetti, Emile Gordon, Bruna Bizzarro, Nidhi Gera, Bruno B Andrade, Fabiano Oliveira, Dongying Ma, Teresa C F Assumpção, José M C Ribeiro, Mirna Pena and 8 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.1field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 42 citations in OpenAlex.

  1. Tempol Protects Against Radiation Injury in the Submandibular Gland Through the β-Catenin Signaling Pathway.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026
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  10. Tempol improves redox status in mdx dystrophic diaphragm muscle.International journal of experimental pathology · 2020
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  13. Cell Invasion and Pyruvate Oxidase-Derived HInfection and immunity · 2018
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  18. Study of the effect of extract of Thymus vulgaris on anxiety in male rats.Journal of traditional and complementary medicine · 2016
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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

18 authors at 3 institutions in 2 countries.

Ivo M B FrancischettiLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Emile GordonLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Bruna BizzarroLaboratory of Experimental Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Nidhi GeraLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Bruno B AndradeLaboratory of Parasitic Diseases, NIAID/NIH, Bethesda, Maryland, United States of America.
Fabiano OliveiraLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Dongying MaLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Teresa C F AssumpçãoLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
José M C RibeiroLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Mirna PenaLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Chen-Feng QiLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Ababacar DioufLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Samuel E MoretzLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Carole A LongLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Hans C AckermanLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Susan K PierceLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Anderson Sá-NunesLaboratory of Experimental Immunology, Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Michael WaisbergLaboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America ; University of Virginia, Department of Pathology, Charlottesville, Virginia, United States of America.
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · USUniversidade de São Paulo · BR

Funding

Mali International Center for Excellence in Research: Malaria immunologyZIAAI001064 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI PIERCE, SUSAN · 2009 to 2025
$25.1M
Vector-Borne Diseases: Biology Of Vector Host RelationshipZIAAI000810 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RIBEIRO, JOSE · 2009 to 2025
$20.8M
Nitric Oxide and Endothelial Function in Patients with MalariaZIAAI001150 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ACKERMAN, HANS · 2011 to 2025
$19.4M
Host Immune Responses to Antigens of Malaria ParasitesZIAAI001020 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI LONG, CAROLE · 2009 to 2025
$13.6M
Genetic Factors that Alter Vascular Function in Sickle Cell DiseaseZIAHL006196 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI ACKERMAN, HANS · 2015 to 2017
$6.2M
6 · The paper itself

Abstract

backgroundThe role of intracellular radical oxygen species (ROS) in pathogenesis of cerebral malaria (CM) remains incompletely understood. METHODS AND

findingsWe undertook testing Tempol--a superoxide dismutase (SOD) mimetic and pleiotropic intracellular antioxidant--in cells relevant to malaria pathogenesis in the context of coagulation and inflammation. Tempol was also tested in a murine model of CM induced by Plasmodium berghei Anka infection. Tempol was found to prevent transcription and functional expression of procoagulant tissue factor in endothelial cells (ECs) stimulated by lipopolysaccharide (LPS). This effect was accompanied by inhibition of IL-6, IL-8, and monocyte chemoattractant protein (MCP-1) production. Tempol also attenuated platelet aggregation and human promyelocytic leukemia HL60 cells oxidative burst. In dendritic cells, Tempol inhibited LPS-induced production of TNF-α, IL-6, and IL-12p70, downregulated expression of co-stimulatory molecules, and prevented antigen-dependent lymphocyte proliferation. Notably, Tempol (20 mg/kg) partially increased the survival of mice with CM. Mechanistically, treated mice had lowered plasma levels of MCP-1, suggesting that Tempol downmodulates EC function and vascular inflammation. Tempol also diminished blood brain barrier permeability associated with CM when started at day 4 post infection but not at day 1, suggesting that ROS production is tightly regulated. Other antioxidants-such as α-phenyl N-tertiary-butyl nitrone (PBN; a spin trap), MnTe-2-PyP and MnTBAP (Mn-phorphyrin), Mitoquinone (MitoQ) and Mitotempo (mitochondrial antioxidants), M30 (an iron chelator), and epigallocatechin gallate (EGCG; polyphenol from green tea) did not improve survival. By contrast, these compounds (except PBN) inhibited Plasmodium falciparum growth in culture with different IC50s. Knockout mice for SOD1 or phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91(phox-/-)) or mice treated with inhibitors of SOD (diethyldithiocarbamate) or NADPH oxidase (diphenyleneiodonium) did not show protection or exacerbation for CM.

conclusionResults with Tempol suggest that intracellular ROS contribute, in part, to CM pathogenesis. Therapeutic targeting of intracellular ROS in CM is discussed.

Indexed as

AnimalsAntioxidantsCells, CulturedChemokine CCL2Cyclic N-OxidesDendritic CellsEnzyme-Linked Immunosorbent AssayHumansInterleukin-6Interleukin-8Malaria, CerebralMiceReactive Oxygen SpeciesReal-Time Polymerase Chain ReactionSpin LabelsThromboplastinAntioxidantsChemokine CCL2Cyclic N-OxidesInterleukin-6Interleukin-8Reactive Oxygen SpeciesSpin LabelstempolThromboplastin

Identifiers

PMID24586264
PMCPMC3938406
OpenAlexW2122150334

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Registered trials

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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.