Evidence map›Paper›PMID 35322094›Full record

ArticleScientific reports2022

Glyoxylate protects against cyanide toxicity through metabolic modulation.

Jason R Nielson, Anjali K Nath, Kim P Doane, Xu Shi, Jangwoen Lee, Emily G Tippetts, Kusumika Saha, Jordan Morningstar, Kevin G Hicks, Adriano Chan and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

3 citing papers in PubMed, 10 citations in OpenAlex.

  1. Redirecting Intermediary Metabolism to Counteract Cyanide Poisoning.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  2. Article
  3. 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

24 authors at 11 institutions in 2 countries.

Jason R NielsonDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, 84112, USA.
Anjali K NathDepartment of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA.
Kim P DoaneDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, 84112, USA.
Xu ShiDepartment of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA.
Jangwoen LeeBeckman Laser Institute and Department of Medicine, University of California, Irvine, CA, 92697, USA.
Emily G TippettsDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, 84112, USA.
Kusumika SahaDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Jordan MorningstarDepartment of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA.
Kevin G HicksDepartment of Biochemistry and Howard Hughes Medical Institute, University of Utah, Salt Lake City, USA.
Adriano ChanDepartment of Medicine, University of California, San Diego, CA, 92093, USA.
Yanbin ZhaoDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Amy KellyDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Tara B Hendry-HoferDepartment of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Alyssa WiteofDepartment of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Patrick Y SipsDepartment of Biomolecular Medicine, Ghent University, 9000, Ghent, Belgium.
Sari MahonBeckman Laser Institute and Department of Medicine, University of California, Irvine, CA, 92697, USA.
Vikhyat S BebartaDepartment of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
Vincent Jo DavissonDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, 47907, USA.
Gerry R BossDepartment of Medicine, University of California, San Diego, CA, 92093, USA.
Jared RutterDepartment of Biochemistry and Howard Hughes Medical Institute, University of Utah, Salt Lake City, USA.
Calum A MacRaeDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Matthew BrennerBeckman Laser Institute and Department of Medicine, University of California, Irvine, CA, 92697, USA.
Robert E GersztenDepartment of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, 02115, USA.
Randall T PetersonDepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake City, UT, 84112, USA. randall.peterson@pharm.utah.edu.
University of Utah · USBrigham and Women's Hospital · USUniversity of Colorado Denver · USBeckman Laser Institute and Medical Clinic · USBeth Israel Deaconess Medical Center · USBroad Institute · USUniversity of California, San Diego · USGhent University · BEHoward Hughes Medical Institute · USPurdue University West Lafayette · USUniversity of California, Irvine · US

Funding

Training & Education CoreU54NS112107 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI GERSZTEN, ROBERT E · 2019 to 2023
$16.0M
Validating promising drug candidates in mammalian models of CN poisoningU54NS079201 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI PETERSON, RANDALL T, PETERSON, RAYMOND J · 2012 to 2016
$12.6M
Interdisciplinary Training Program in MetabolismT32DK091317 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI SCOTT A SUMMERS · 2011 to 2026
$4.8M
Marie Curie 794365NIH HHS U54NS112107NINDS NIH HHS U54 NS112107
6 · The paper itself

Abstract

Although cyanide's biological effects are pleiotropic, its most obvious effects are as a metabolic poison. Cyanide potently inhibits cytochrome c oxidase and potentially other metabolic enzymes, thereby unleashing a cascade of metabolic perturbations that are believed to cause lethality. From systematic screens of human metabolites using a zebrafish model of cyanide toxicity, we have identified the TCA-derived small molecule glyoxylate as a potential cyanide countermeasure. Following cyanide exposure, treatment with glyoxylate in both mammalian and non-mammalian animal models confers resistance to cyanide toxicity with greater efficacy and faster kinetics than known cyanide scavengers. Glyoxylate-mediated cyanide resistance is accompanied by rapid pyruvate consumption without an accompanying increase in lactate concentration. Lactate dehydrogenase is required for this effect which distinguishes the mechanism of glyoxylate rescue as distinct from countermeasures based solely on chemical cyanide scavenging. Our metabolic data together support the hypothesis that glyoxylate confers survival at least in part by reversing the cyanide-induced redox imbalances in the cytosol and mitochondria. The data presented herein represent the identification of a potential cyanide countermeasure operating through a novel mechanism of metabolic modulation.

Indexed as

GlyoxylatesZebrafishAnimalsCyanidesMammalsPyruvic AcidCyanidesGlyoxylatesglyoxylic acidPyruvic Acid

Identifiers

PMID35322094
PMCPMC8943054
OpenAlexW4220791876

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.