Evidence map›Paper›PMID 26990293›Full record

ArticlePloS one2016

Impact of Superoxide Dismutase Mimetic AEOL 10150 on the Endothelin System of Fischer 344 Rats.

Devi Ganesh, Prem Kumarathasan, Errol M Thomson, Carly St-Germain, Erica Blais, James Crapo, Renaud Vincent

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 26% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Oxidative Stress: A Unifying Paradigm in Hypertension.The Canadian journal of cardiology · 2020
    Review
  7. 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 2 countries.

Devi GaneshDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Prem KumarathasanEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Errol M ThomsonEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Carly St-GermainEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
Erica BlaisEnvironmental Health Science and Research Bureau, Environmental and Radiation Health Sciences Directorate, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, Canada.
James CrapoNational Jewish Health, Denver, Colorado, United States of America.
Renaud VincentDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Health Canada · CANational Jewish Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Endothelin-1 is a potent vasoconstrictor and mitogenic peptide involved in the regulation of vasomotor tone and maintenance of blood pressure. Oxidative stress activates the endothelin system, and is implicated in pulmonary and cardiovascular diseases including hypertension, congestive heart failure, and atherosclerosis. Superoxide dismutase mimetics designed with the aim of treating diseases that involve reactive oxygen species in their pathophysiology may exert a hypotensive effect, but effects on the endothelin system are unknown. Our objective was to determine the effect of the superoxide dismutase mimetic AEOL 10150 on the basal endothelin system in vivo. Male Fischer-344 rats were injected subcutaneously with 0, 2 or 5 mg/kg body weight of AEOL 10150 in saline. Plasma oxidative stress markers and endothelins (bigET-1, ET-1, ET-2, ET-3) as well as lung and heart endothelin/nitric oxide system gene expressions were measured using HPLC-Coularray, HPLC-Fluorescence and RT-PCR respectively. AEOL 10150 reduced (p<0.05) the circulating levels of isoprostane (-25%) and 3-nitrotyrosine (-50%) measured in plasma 2h and 24h after treatment, confirming delivery of a physiologically-relevant dose and the potent antioxidant activity of the drug. The reduction in markers of oxidative stress coincided with sustained 24h decrease (p<0.05) of plasma levels of ET-1 (-50%) and ET-3 (-10%). Expression of preproET-1 and endothelin converting enzyme-1 mRNA were not altered significantly in the lungs. However preproET-1 (not significant) and ECE-1 mRNA (p<0.05) were increased (10-25%) in the heart. Changes in the lungs included decrease (p<0.05) of mRNA for the ET-1 clearance receptor ETB and the vasoconstriction-signaling ETA receptor (-30%), and an early surge of inducible nitric oxide synthase expression followed by sustained decrease (-40% after 24 hours). The results indicate that interception of the endogenous physiological flux of reactive nitrogen species and reactive oxygen species in rats impacts the endothelin/nitric oxide system, supporting a homeostatic relationship between those systems.

Indexed as

AnimalsAntioxidantsBiomarkersChromatography, High Pressure LiquidEndothelinsHomeostasisMaleMetalloporphyrinsOxidative StressRats, Inbred F344Reactive Nitrogen SpeciesReactive Oxygen SpeciesSuperoxide DismutaseVasoconstrictionAEOL 10150AntioxidantsBiomarkersEndothelinsMetalloporphyrinsReactive Nitrogen SpeciesReactive Oxygen SpeciesSuperoxide Dismutase

Identifiers

PMID26990293
PMCPMC4798617
OpenAlexW2297554234

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.