ArticleInternational journal of molecular sciences2022
Methotrexate-Induced Liver Injury Is Associated with Oxidative Stress, Impaired Mitochondrial Respiration, and Endoplasmic Reticulum Stress In Vitro.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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.
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Who cites it
41 citing papers in PubMed.
- Piribedil attenuates methotrexate-induced nephrotoxicity in rats: associated changes in miR-205/EGLN2, Nrf2, and PERK/ATF4/CHOP-related stress responses.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Therapeutic effects of Rosmarinus officinalis against methotrexate-induced submandibular salivary gland injury in male albino rats.Journal of molecular histology · 2026Article
- An Integrated DNA Nanoprobe for Intranuclear Imaging and In Situ Profiling of OGG1 Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loureirin B Attenuates Methotrexate-Induced Liver Injury Associated with Oxidative Stress, SIRT1 Alterations, and TGF-β/SMAD3-Related Profibrotic Responses.Pharmaceuticals (Basel, Switzerland) · 2026Article
- L-carnitine protects against methotrexate-induced hepatotoxicity via regulation of apoptosis and metabolic pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- From Genotype to Functional Risk: A Multi-Omic Approach to Predicting Thiopurine and Methotrexate Co-Therapy-Induced Liver Injury.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Liposomal Myricetin Nanoantioxidants Attenuate Methotrexate-Induced Hepatotoxicity by Modulating Oxidative Stress, Inflammation, and Apoptosis in Rats.Antioxidants (Basel, Switzerland) · 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
- Late hepatotoxicity after treatment for childhood cancer.World journal of hepatology · 2026Review
- Modulatory effects of Withania somnifera supplementation on p38 MAPK/NF-κB/COX-2 and TRPC1/CHOP signaling pathways in methotrexate-induced parotid and submandibular salivary gland toxicity in rats.Journal of molecular histology · 2026Article
- Mitigative effects of Otilonium Bromide on methotrexate-induced hepatic damage in rats.BMC research notes · 2026Article
- Hepatotoxicity Risk of Isoniazid in Patients with Autoimmune Rheumatic Diseases and Prior Liver Injury Due to Disease-Modifying Antirheumatic Drugs: A Single-Center Experience and Literature Review.Journal of clinical medicine · 2026Article
- Dioscin in liver diseases: pharmacological mechanisms, translational potential and future perspectives.Frontiers in pharmacology · 2026Review
- Pharmacological Mechanisms of Phytochemicals and Pharmaceutical Agents in Protecting Against Methotrexate-Induced Liver Injury.Oxidative medicine and cellular longevity · 2026Review
- Therapeutic Potential of Bee Venom and Capsicum annum Hydroethanolic Extract in Experimental Model of Rheumatoid Arthritis in Male Rats.Mediators of inflammation · 2026Article
- Renal protective effect of coenzyme Q10 against methotrexate-induced nephrotoxicity in rats.Open veterinary journal · 2026Article
- Dapansutrile mitigates methotrexate-induced hepatotoxicity in rats: roles of inflammation, oxidative stress, pyroptosis, and autophagy.Frontiers in pharmacology · 2026Article
- Mechanistic insights into the hepatoprotective role of rabeprazole against cyclophosphamide-induced hepatotoxicity via AMPK/SIRT1 activation and suppression of TLR4/NF-κB and MAPK pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Protodioscin enhances Methotrexate-induced senescence and senolytic activity in HepG2 liver cancer spheroids by modulating cell cycle regulators and the TGF-β/p-Smad2-4 signaling pathway.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Low-dose methotrexate (MTX) is a standard therapy for rheumatoid arthritis due to its low cost and efficacy. Despite these benefits, MTX has been reported to cause chronic drug-induced liver injury, namely liver fibrosis. The hallmark of liver fibrosis is excessive scarring of liver tissue, triggered by hepatocellular injury and subsequent activation of hepatic stellate cells (HSCs). However, little is known about the precise mechanisms through which MTX causes hepatocellular damage and activates HSCs. Here, we investigated the mechanisms leading to hepatocyte injury in HepaRG and used immortalized stellate cells (hTERT-HSC) to elucidate the mechanisms leading to HSC activation by exposing mono- and co-cultures of HepaRG and hTERT-HSC to MTX. The results showed that at least two mechanisms are involved in MTX-induced toxicity in HepaRG: (i) oxidative stress through depletion of glutathione (GSH) and (ii) impairment of cellular respiration in a GSH-independent manner. Furthermore, we measured increased levels of endoplasmic reticulum (ER) stress in activated HSC following MTX treatment. In conclusion, we established a human-relevant in vitro model to gain mechanistical insights into MTX-induced hepatotoxicity, linked oxidative stress in HepaRG to a GSH-dependent and -independent pathway, and hypothesize that not only oxidative stress in hepatocytes but also ER stress in HSCs contribute to MTX-induced activation of HSCs.
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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.