ArticleBritish journal of pharmacology2003
The anti-inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen species.
Article in British journal of pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- Clinical efficacy and adverse events of baricitinib treatment for coronavirus disease-2019 (COVID-19): A systematic review and meta-analysis.Journal of medical virology · 2022Pooled it
- The number of circulating monocytes as biomarkers of the clinical response to methotrexate in untreated patients with rheumatoid arthritis.Journal of translational medicine · 2015Trial
- Obeticholic acid attenuates complete freund's adjuvant-induced arthritis in rats through FXR-mediated modulation of TGF-β/TAK1/MKK3/p38 MAPK signaling, inflammation, and oxidative stress.Inflammopharmacology · 2026Article
- Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Methotrexate potentiates oxidative stress-mediated transdifferentiation and metabolic reprogramming of neutrophils.Journal of bioenergetics and biomembranes · 2026Article
- Pregabalin mitigates methotrexate-induced pulmonary injury via suppression of inflammatory and endothelial activation mechanisms: a histopathological and immunohistochemical approach.Discover oncology · 2026Article
- ROS-Scavenging Bamboo-Derived Carbon Dot-Methotrexate Nanocomposite Ameliorates Rheumatoid Arthritis through Dual Therapeutic Mechanisms.ACS omega · 2026Article
- Effect of curcumin on methotrexate-induced ovarian damage and follicle reserve in rats: the role of PARP-1 and P53.Annals of medicine · 2025Article
- PV-10 Triggers Immunogenic Cell Death in Head and Neck Squamous Cell Carcinoma via Endoplasmic Reticulum Stress and Apoptosis.Molecular cancer therapeutics · 2025Article
- Low Dose Methotrexate Has Divergent Effects on Cycling and Resting Human Hematopoietic Stem and Progenitor Cells.Clinical and translational science · 2025Article
- Dual Targeting Biomimetic Carrier-Free Nanosystems for Photo-Chemotherapy of Rheumatoid Arthritis via Macrophage Apoptosis and Re-Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Extracellular vesicles released by ALL patients contain HNE-adducted proteins: Implications of collateral damage.Free radical biology & medicine · 2025Article
- The Pathophysiological Role of Mitochondrial Oxidative Stress in Rheumatic Diseases.Journal of inflammation research · 2025Review
- Investigating the Anti-inflammatory Effect of Quinoline Derivative: N1-(5-methyl-5H-indolo[2,3-b]quinolin-11-yl)benzene-1,4-diamine Hydrochloride Loaded Soluble Starch Nanoparticles Against Methotrexate-induced Inflammation in Experimental Model.Biological procedures online · 2024Article
- Mechanistic aspects of ameliorative effects of Eicosapentanoic acid ethyl ester on methotrexate-evoked testiculopathy in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Peripheral blood cellular dynamics of rheumatoid arthritis treatment informs about efficacy of response to disease modifying drugs.Scientific reports · 2023Article
- DHFR Inhibitors Display a Pleiotropic Anti-Viral Activity against SARS-CoV-2: Insights into the Mechanisms of Action.Viruses · 2023Article
- Application of T-cell receptor repertoire as a novel monitor in dynamic tracking and assessment: A cohort-study based on RA patients.Journal of cellular and molecular medicine · 2022Article
- The Protective Effects of Nutraceutical Components in Methotrexate-Induced Toxicity Models-An Overview.Microorganisms · 2022Review
- Reduced nicotinamide adenine dinucleotide phosphate in redox balance and diseases: a friend or foe?Acta pharmacologica Sinica · 2022Review
18 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1 The mechanism of action by which methotrexate (MTX) exerts its anti-inflammatory and immunosuppressive effects remains unclear. The aim of this study is to investigate the hypothesis that MTX exerts these effects via the production of reactive oxygen species (ROS). 2 Addition of MTX (100 nM-10 micro M) to U937 monocytes induced a time and dose dependent increase in cytosolic peroxide [peroxide](cyt) from 6-16 h. MTX also caused corresponding monocyte growth arrest, which was inhibited (P<0.05) by pre-treatment with N-acetylcysteine (NAC; 10 mM) or glutathione (GSH; 10 mM). In contrast, MTX induction of [peroxide](cyt) in Jurkat T cells was more rapid (4 h; P<0.05), but was associated with significant apoptosis at 16 h at all doses tested (P<0.05) and was significantly inhibited by NAC or GSH (P<0.05). 3 MTX treatment of monocytes (10 nM-10 micro M) for 16 h significantly reduced total GSH levels (P<0.05) independently of dose (P>0.05). However, in T-cells, GSH levels were significantly elevated following 30 nM MTX treatment (P<0.05) but reduced by doses exceeding 1 micro M compared to controls (P<0.05). 4 MTX treatment significantly reduced monocyte adhesion to 5 h and 24 h LPS (1 micro g ml(-1)) activated human umbilical vein endothelial cells (HUVEC; P<0.05) but not to resting HUVEC. Pre-treatment with GSH prevented MTX-induced reduction in adhesion. 5 In conclusion, ROS generation by MTX is important for cytostasis in monocytes and cytotoxicity T-cells. Furthermore, MTX caused a reduction in monocyte adhesion to endothelial cells, where the mechanism of MTX action requires the production of ROS. Therefore its clinical efficacy can be attributed to multiple targets.
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