ArticleRedox biology2017
Direct antioxidant properties of methotrexate: Inhibition of malondialdehyde-acetaldehyde-protein adduct formation and superoxide scavenging.
Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Malondialdehyde-acetaldehyde modified macromolecules and resulting autoantibodies in rheumatoid arthritis pathogenesis: a Systematic Literature Review.Frontiers in immunology · 2025Pooled it
- 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
- Antioxidant Polymeric and Non-Polymeric Nanoformulations for the Treatment of Autoimmune Diseases.Current issues in molecular biology · 2026Review
- Citrullinated and Malondialdehyde-Acetaldehyde-Modified Fibrinogen Activates Macrophages and Promotes Coronary Endothelial Cell Inflammation.Current issues in molecular biology · 2025Article
- Risk and temporal trends of heart failure subtypes in rheumatoid arthritis.Seminars in arthritis and rheumatism · 2025Article
- Mesoporous polydopamine@CeOiScience · 2025Article
- Association between cerebral small vessel disease and malnutrition risk: a retrospective cross-sectional study.Frontiers in neurology · 2025Article
- Effects of Malondialdehyde on Growth Performance, Gastrointestinal Health, and Muscle Quality of Striped Catfish (Antioxidants (Basel, Switzerland) · 2024Article
- Methotrexate and the Risk of Dementia: A Two-Sample Mendelian Randomization Study.Neurology and therapy · 2024Article
- Quillaja saponin mitigates methotrexate-provoked renal injury; insight into Nrf-2/Keap-1 pathway modulation with suppression of oxidative stress and inflammation.Journal of pharmaceutical health care and sciences · 2024Article
- Effects of Different Therapeutic Approaches on Redox Balance in Psoriatic Patients.Biomedicines · 2024Article
- Article
- Formulation of a dual drug-loaded nanoparticulate co-delivery hydrogel system and its validation in rheumatoid arthritis animal model.Drug delivery · 2023Article
- Lipid peroxidation in osteoarthritis: focusing on 4-hydroxynonenal, malondialdehyde, and ferroptosis.Cell death discovery · 2023Review
- Prodrug Integrated Envelope on Probiotics to Enhance Target Therapy for Ulcerative Colitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Disease-modifying anti-rheumatic drugs improve the cardiovascular profile in patients with rheumatoid arthritis.Frontiers in cardiovascular medicine · 2022Review
- Psoriasis between Autoimmunity and Oxidative Stress: Changes Induced by Different Therapeutic Approaches.Oxidative medicine and cellular longevity · 2022Review
- Investigating changes in disease activity as a mediator of cardiovascular risk reduction with methotrexate use in rheumatoid arthritis.Annals of the rheumatic diseases · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Methotrexate (MTX) is an immunosuppressant commonly used for the treatment of autoimmune diseases. Recent observations have shown that patients treated with MTX also exhibit a reduced risk for the development of cardiovascular disease (CVD). Although MTX reduces systemic inflammation and tissue damage, the mechanisms by which MTX exerts these beneficial effects are not entirely known. We have previously demonstrated that protein adducts formed by the interaction of malondialdehyde (MDA) and acetaldehyde (AA), known as MAA-protein adducts, are present in diseased tissues of individuals with rheumatoid arthritis (RA) or CVD. In previously reported studies, MAA-adducts were shown to be highly immunogenic, supporting the concept that MAA-adducts not only serve as markers of oxidative stress but may have a direct role in the pathogenesis of inflammatory diseases. Because MAA-adducts are commonly detected in diseased tissues and are proposed to mitigate disease progression in both RA and CVD, we tested the hypothesis that MTX inhibits the generation of MAA-protein adducts by scavenging reactive oxygen species. Using a cell free system, we found that MTX reduces MAA-adduct formation by approximately 6-fold, and scavenges free radicals produced during MAA-adduct formation. Further investigation revealed that MTX directly scavenges superoxide, but not hydrogen peroxide. Additionally, using the Nrf2/ARE luciferase reporter cell line, which responds to intracellular redox changes, we observed that MTX inhibits the activation of Nrf2 in cells treated with MDA and AA. These studies define previously unrecognized mechanisms by which MTX can reduce inflammation and subsequent tissue damage, namely, scavenging free radicals, reducing oxidative stress, and inhibiting MAA-adduct formation.
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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.