ArticlePloS one2012
Neuroprotective actions of methylene blue and its derivatives.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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.
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.
Who cites it
70 citing papers in PubMed, 146 citations in OpenAlex.
- Methylene blue confers protection against hepatotoxicity induced by Cisplatin; the involvement of oxidative stress, apoptosis and NCOA4-mediated ferritinophagy.Molecular biology reports · 2026Article
- Mitochondrial and Antioxidant Activity as the Basis of the Neuroprotective Effect of Potential Multitarget Drugs for the Treatment of Neurodegenerative Diseases.Current neuropharmacology · 2026Review
- Methylene Blue for Prevention of Perioperative Neurocognitive Disorders: Mechanisms and Recent Clinical Evidence.Drug design, development and therapy · 2026Review
- Hepatoprotection by Methylene Blue Against Doxorubicin Toxicity Through Coordinated Modulation of Oxidative Stress, ER Stress, and Apoptotic Pathways.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Methylene Blue Mitigates Doxorubicin-Induced Cardiotoxicity via KEAP1/NRF2/GPX-4/Caspase3 Modulation.International journal of molecular sciences · 2025Article
- Oxidized Carbon Nanoparticles Enhance Cellular Energetics With Application to Injured Brain.Advanced healthcare materials · 2025Article
- Article
- Application of methylene blue for the prevention and treatment of COVID-19: A narrative review.Iranian journal of basic medical sciences · 2024Review
- Evaluation of topical methylene blue nanoemulsion for wound healing in diabetic mice.Pharmaceutical biology · 2023Article
- Measuring Constipation in a Drosophila Model of Parkinson's Disease.Journal of visualized experiments : JoVE · 2023Article
- Toluidine blue O directly and photodynamically impairs the bioenergetics of liver mitochondria: a potential mechanism of hepatotoxicity.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2023Article
- Therapeutics of Alzheimer's Disease: Recent Developments.Antioxidants (Basel, Switzerland) · 2022Review
- Methylene blue: a controversial diagnostic acid and medication?Toxicology research · 2022Review
- Review
- New insights into targeting mitochondria in ischemic injury.Apoptosis : an international journal on programmed cell death · 2021Review
- Role of pyroptosis in spinal cord injury and its therapeutic implications.Journal of advanced research · 2021Review
- Head-to-Head Comparison of Sedation and Somnolence Among 37 Antipsychotics in Schizophrenia, Bipolar Disorder, Major Depression, Autism Spectrum Disorders, Delirium, and Repurposed in COVID-19, Infectious Diseases, and Oncology From the FAERS, 2004-2020.Frontiers in pharmacology · 2021Article
- The effect of levomepromazine on the healthy and injured developing mouse brain - AnIBRO reports · 2020Article
- Antiferroptotic Activity of Phenothiazine Analogues: A Novel Therapeutic Strategy for Oxidative Stress Related Disease.ACS medicinal chemistry letters · 2020Article
- Antidotal effects of methylene blue against cyanide neurological toxicity: in vivo and in vitro studies.Annals of the New York Academy of Sciences · 2020Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Methylene blue (MB), the first lead chemical structure of phenothiazine and other derivatives, is commonly used in diagnostic procedures and as a treatment for methemoglobinemia. We have previously demonstrated that MB could function as an alternative mitochondrial electron transfer carrier, enhance cellular oxygen consumption, and provide protection in vitro and in rodent models of Parkinson's disease and stroke. In the present study, we investigated the structure-activity relationships of MB in vitro using MB and six structurally related compounds. MB reduces mitochondrial superoxide production via alternative electron transfer that bypasses mitochondrial complexes I-III. MB mitigates reactive free radical production and provides neuroprotection in HT-22 cells against glutamate, IAA and rotenone toxicity. Distinctly, MB provides no protection against direct oxidative stress induced by glucose oxidase. Substitution of a side chain at MB's 10-nitrogen rendered a 1000-fold reduction of the protective potency against glutamate neurototoxicity. Compounds without side chains at positions 3 and 7, chlorophenothiazine and phenothiazine, have distinct redox potentials compared to MB and are incapable of enhancing mitochondrial electron transfer, while obtaining direct antioxidant actions against glutamate, IAA, and rotenone insults. Chlorophenothiazine exhibited direct antioxidant actions in mitochondria lysate assay compared to MB, which required reduction by NADH and mitochondria. MB increased complex IV expression and activity, while 2-chlorphenothiazine had no effect. Our study indicated that MB could attenuate superoxide production by functioning as an alternative mitochondrial electron transfer carrier and as a regenerable anti-oxidant in mitochondria.
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What OpenQuestion holds
Registered trials
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.