ArticlePloS one2015
Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Therapeutic Potential of Stem Cells in the Treatment and Management of Immunomodulatory Disorders.Current pharmaceutical design · 2026Pooled it
- Therapeutic effects of Rosmarinus officinalis against methotrexate-induced submandibular salivary gland injury in male albino rats.Journal of molecular histology · 2026Article
- Agomelatine Alleviates Methotrexate-Induced Lung Injury by Concurrently Inhibiting CD45/CD68-Positive Immune Cell Infiltration and Modulating the BAX/BCL2 Apoptosis Pathway.Journal of applied toxicology : JAT · 2026Article
- Cellular Anti-Apoptotic Effects of Dapagliflozin in Methotrexate-Induced Liver Toxicity: Bax/Bcl-2/Cyt-C/Cas-9/Cas-3 Signaling Pathway.International journal of molecular sciences · 2026Article
- Connection Between Mitochondria and Rheumatoid Arthritis and Osteoarthritis: Personalized Treatment Strategies.Current pharmaceutical design · 2026Review
- Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy.Frontiers in pharmacology · 2026Review
- Mitochondria as a Disease-Relevant Organelle in Rheumatoid Arthritis: A Key Breakout in Fight Against the Disease.Biomedicines · 2025Review
- Possible hemoglobin enhancing effect of phytol in methotrexate-induced folate deficientPharmaceutical science advances · 2024Article
- L-methionine protects against nephrotoxicity induced by methotrexate through modulation of redox status and inflammation.Redox report : communications in free radical research · 2023Article
- Hepatotoxicity from high-dose methotrexate in primary central nervous system lymphoma.Neuro-oncology practice · 2023Article
- Discovery of Pyrimidine- and Coumarin-Linked Hybrid Molecules as Inducers of JNK Phosphorylation through ROS Generation in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2023Article
- Apoptosis versus necrosis in tubal ectopic pregnancies following Methotrexate.International journal of experimental pathology · 2023Article
- Review
- Mitochondrial Dysfunction in Rheumatoid Arthritis.Biomolecules · 2022Review
- Glutathione levels are associated with methotrexate resistance in acute lymphoblastic leukemia cell lines.Frontiers in oncology · 2022Article
- Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis.International journal of molecular sciences · 2021Review
- Psoriatic disease is associated with systemic inflammation, endothelial activation, and altered haemostatic function.Scientific reports · 2021Article
- Mitochondria as Key Players in the Pathogenesis and Treatment of Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Article
- Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells.Bioscience reports · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 μM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to ΔΨm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions.
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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.