Evidence map›Paper›PMID 29451035›Full record

ArticleClinical toxicology (Philadelphia, Pa.)2018

Revisiting the physiological effects of methylene blue as a treatment of cyanide intoxication.

Philippe Haouzi, Maxime Gueguinou, Takashi Sonobe, Annick Judenherc-Haouzi, Nicole Tubbs, Mohamed Trebak, Joseph Cheung, Frederic Bouillaud

Abstract read
In one paragraph

Article in Clinical toxicology (Philadelphia, Pa.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
5.4field-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

15 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Redirecting Intermediary Metabolism to Counteract Cyanide Poisoning.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Antidotal Effects of the Phenothiazine Chromophore Methylene Blue Following Cyanide Intoxication.Toxicological sciences : an official journal of the Society of Toxicology · 2019
    Article
  14. Article
  15. Methylene blue counteracts cyanide cardiotoxicity: cellular mechanisms.Journal of applied physiology (Bethesda, Md. : 1985) · 2018
    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

8 authors at 4 institutions in 2 countries.

Philippe Haouzia Division of Pulmonary and Critical Care Medicine , Pennsylvania State University College of Medicine , Hershey , PA , USA.
Maxime Gueguinoub Department of Physiology , Pennsylvania State University College of Medicine , Hershey , PA , USA.
Takashi Sonobea Division of Pulmonary and Critical Care Medicine , Pennsylvania State University College of Medicine , Hershey , PA , USA.
Annick Judenherc-Haouzid Heart and Vascular Institute, Pennsylvania State University College of Medicine , Hershey , PA , USA.
Nicole Tubbsa Division of Pulmonary and Critical Care Medicine , Pennsylvania State University College of Medicine , Hershey , PA , USA.
Mohamed Trebakb Department of Physiology , Pennsylvania State University College of Medicine , Hershey , PA , USA.
Joseph Cheungc Department of Medicine , Lewis Katz School of Medicine of Temple University , Philadelphia , PA , USA.
Frederic Bouillaudf Institut Cochin, INSERM U1016-CNRS UMR8104, Université Paris Descartes , Paris , France.
Pennsylvania State University · USInstitut Cochin · FRPenn State Milton S. Hershey Medical Center · USTemple University · US

Funding

Receptor-regulated Ca2+ Entry Pathways in Smooth MuscleR01HL097111 · NHLBI · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI TREBAK, MOHAMED · 2010 to 2019
$3.7M
Leukotriene C4 and STIM/Orai channels in airway smooth muscle remodelingR01HL123364 · NHLBI · STATE UNIVERSITY OF NEW YORK AT ALBANY · PI TREBAK, MOHAMED · 2014 to 2017
$1.5M
Effects of acute administration of the Phenothiazinium Chromophore Methylene blue during life threatening cyanide intoxicationR21NS098991 · NINDS · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI HAOUZI, PHILIPPE A · 2016 to 2017
$442k
NHLBI NIH HHS R01 HL097111NHLBI NIH HHS R01 HL123364NINDS NIH HHS R21 NS098991
6 · The paper itself

Abstract

backgroundAlthough methylene blue (MB) had long been proposed to counteract the effects of cyanide (CN) intoxication, research on its mechanisms of action and efficacy has been abandoned for decades. Recent studies on the benefits of MB in post-anoxic injuries have prompted us to reexamine the relevance of this historical observation.

methodsOur study was performed in adult male Sprague-Dawley rats and on HEK293T epithelial cells. First, the effects and toxicity of MB (0-80 mg/kg) on circulation and metabolism were established in four urethane-anesthetized rats. Then nine rats received a lethal infusion of a solution of KCN (0.75 mg/kg/min) and were treated by either saline or MB, at 20 mg/kg, a dose that we found to be innocuous in rat and to correspond to a dose of about 4 mg/kg in humans. MB was also administered 5 min after the end of a sub-lethal exposure to CN in a separate group of 10 rats. In addition, ATP/ADP ratio, ROS production, mitochondrial membrane potential (Δψm) and cellular O

resultsMethylene blue was found to be innocuous up to 50 mg/kg. KCN infusion (0.75 mg/kg/min) killed all animals within 7-8 min. MB (20 mg/kg) administered at the same time restored blood pressure, cardiac contractility and limited O

conclusionsThe present observations should make us consider the potential interest of MB in the treatment of CN intoxication. The mechanisms of the antidotal properties of MB cannot be accounted for by the creation of a cyanomethemoglobinemia, rather its protective effects appears to be related to the unique properties of this redox dye, which, depending on the dose, could directly oppose some of the consequences of the metabolic depression produced by CN at the cellular level.

Indexed as

AnimalsAntidotesCyanidesDose-Response Relationship, DrugHEK293 CellsHumansMaleMethylene BluePoisoningRatsRats, Sprague-DawleyAntidotesCyanidesMethylene Bluecirculatory failureCyanide intoxicationmethylene bluemitochondrial poisonsredox dyes

Identifiers

PMID29451035
PMCPMC6086742
OpenAlexW2794011215

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.