Evidence map›Paper›PMID 32720192›Full record

ArticleArchives of toxicology2020

Discovery of treatment for nerve agents targeting a new metabolic pathway.

Trevor Glaros, Elizabeth S Dhummakupt, Gabrielle M Rizzo, Ethan McBride, Daniel O Carmany, Linnzi K M Wright, Jeffry S Forster, Julie A Renner, Ruth W Moretz, Russell Dorsey and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Archives of toxicology, 2020. 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
–field-weighted citation impact
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.

  1. Article
  2. Article
  3. Article
  4. 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

17 authors.

Trevor GlarosResearch and Technology Directorate, BioSciences Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Building E3150, Aberdeen Proving Ground, Gunpowder, MD, 21010, USA. tglaros@lanl.gov.
Elizabeth S DhummakuptResearch and Technology Directorate, BioSciences Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Building E3150, Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Gabrielle M RizzoExcet, Inc., 6225 Brandon Ave, Suite 360, Springfield, VA, 22150, USA.
Ethan McBrideResearch and Technology Directorate, BioSciences Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Building E3150, Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Daniel O CarmanyExcet, Inc., 6225 Brandon Ave, Suite 360, Springfield, VA, 22150, USA.
Linnzi K M WrightResearch and Technology Directorate, Toxicology and Obscurants Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Jeffry S ForsterResearch and Technology Directorate, Toxicology and Obscurants Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Julie A RennerResearch and Technology Directorate, Toxicology and Obscurants Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Ruth W MoretzResearch and Technology Directorate, Toxicology and Obscurants Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Russell DorseyResearch and Technology Directorate, Toxicology and Obscurants Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Mark R MartenDepartment of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County (UMBC), Engineering Building, Baltimore, MD, USA.
Walker HusoDepartment of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County (UMBC), Engineering Building, Baltimore, MD, USA.
Alexander DoanDepartment of Chemical, Biochemical and Environmental Engineering, University of Maryland, Baltimore County (UMBC), Engineering Building, Baltimore, MD, USA.
Carrie D DorseyKirk U.S. Army Health Clinic, 6455 Machine Rd., Aberdeen Proving Ground, Gunpowder, MD, 21005, USA.
Christopher PhillipsResearch and Technology Directorate, Toxicology and Obscurants Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Bernard BentonResearch and Technology Directorate, Toxicology and Obscurants Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Aberdeen Proving Ground, Gunpowder, MD, 21010, USA.
Phillip M MachResearch and Technology Directorate, BioSciences Division, Combat Capabilities Development Command (CCDC) Chemical Biological Center, 5183 Blackhawk Rd., Building E3150, Aberdeen Proving Ground, Gunpowder, MD, 21010, USA. phillip.m.mach.civ@mail.mil.ORCID http://orcid.org/0000-0003-0842-3844

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The inhibition of acetylcholinesterase is regarded as the primary toxic mechanism of action for chemical warfare agents. Recently, there have been numerous reports suggesting that metabolic processes could significantly contribute to toxicity. As such, we applied a multi-omics pipeline to generate a detailed cascade of molecular events temporally occurring in guinea pigs exposed to VX. Proteomic and metabolomic profiling resulted in the identification of several enzymes and metabolic precursors involved in glycolysis and the TCA cycle. All lines of experimental evidence indicated that there was a blockade of the TCA cycle at isocitrate dehydrogenase 2, which converts isocitrate to α-ketoglutarate. Using a primary beating cardiomyocyte cell model, we were able to determine that the supplementation of α-ketoglutarate subsequently rescued cells from the acute effects of VX poisoning. This study highlights the broad impacts that VX has and how understanding these mechanisms could result in new therapeutics such as α-ketoglutarate.

Indexed as

AcetylcholinesteraseAnimalsChemical Warfare AgentsGuinea PigsMetabolic Networks and PathwaysMetabolomicsNerve AgentsPoisoningProteomeProteomicsAcetylcholinesteraseChemical Warfare AgentsNerve AgentsProteomea-KetoglutarateCardiomyocytesGlycolysisMetabolomicsProteomicsVX poisoning

Identifiers

PMID32720192
PMCPMC7415758

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.