ArticleDaru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences2019
Ellagic acid reduces methotrexate-induced apoptosis and mitochondrial dysfunction via up-regulating Nrf2 expression and inhibiting the IĸBα/NFĸB in rats.
Article in Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
- L-Methionine attenuates methotrexate-induced cardiotoxicity by modulating oxidative stress, inflammation, and dyslipidemia in rats.Toxicology reports · 2026Article
- Mitochondrial protective effects of ellagic acid in a rat model of sporadic Alzheimer's disease induced by STZ.Scientific reports · 2026Article
- Therapeutic potential of β-sitosterol in methotrexate-induced liver injury: association with STING and ERK-1 pathways.BMC gastroenterology · 2026Article
- Pharmacological Mechanisms of Phytochemicals and Pharmaceutical Agents in Protecting Against Methotrexate-Induced Liver Injury.Oxidative medicine and cellular longevity · 2026Review
- Modulation of AMPK by esomeprazole and canagliflozin mitigates methotrexate-induced hepatotoxicity: involvement of MAPK/JNK/ERK, JAK1/STAT3, and PI3K/Akt signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Therapeutic Potential of Ellagic Acid in Liver Diseases.Molecules (Basel, Switzerland) · 2025Review
- Ivermectin Attenuates Methotrexate-Induced Liver Fibrosis by Reducing TGF-β and Syndecan-1 Expression.Medicina (Kaunas, Lithuania) · 2025Article
- The Protective Effect of Ellagic Acid and Its Metabolites Against Organ Injuries: A Mitochondrial Perspective.Food science & nutrition · 2025Review
- Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions.Oncology and therapy · 2024Review
- Regulation Progression on Ellagic Acid Improving Poultry Production Performance by Regulating Redox Homeostasis, Inflammatory Response, and Cell Apoptosis.Animals : an open access journal from MDPI · 2024Review
- Mucoprotective effect of ellagic acid in 5 fluorouracil-induced intestinal mucositis model.Journal of medicine and life · 2023Article
- Article
- Dihydromyricetin Modulates Nrf2 and NF-κB Crosstalk to Alleviate Methotrexate-Induced Lung Toxicity.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Bee Pollen as Functional Food: Insights into Its Composition and Therapeutic Properties.Antioxidants (Basel, Switzerland) · 2023Review
- Mitochondrial Modulators: The Defender.Biomolecules · 2023Review
- Protective effects and therapeutic applications of ellagic acid against natural and synthetic toxicants: A review article.Iranian journal of basic medical sciences · 2022Review
- The molecular biology and therapeutic potential of Nrf2 in leukemia.Cancer cell international · 2022Review
- Procyanidin B2 Alleviates Heat-Induced Oxidative Stress through the Nrf2 Pathway in Bovine Mammary Epithelial Cells.International journal of molecular sciences · 2022Article
- Ellagic Acid Alleviates Oxidative Stress by Mediating Nrf2 Signaling Pathways and Protects against Paraquat-Induced Intestinal Injury in Piglets.Antioxidants (Basel, Switzerland) · 2022Article
- CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe clinical application of methotrexate (MTX), an efficacious cytotoxic drug, is restricted due to its associated liver toxicity. Ellagic acid (EA), a natural polyphenol, possesses hepatoprotective, antioxidant and anti-inflammatory properties.
objectivesThe present study seeks to address the hepatoprotective effects of Ellagic acid (EA) against MTX-mediated oxidative stress (OS) and widen our current knowledge of the underlying molecular mechanisms of MTX toxicity.
methodsWistar rats were orally given EA (5 mg/kg and 10 mg/kg) for 10 successive days and at the end of the third day they were administered a single dose of MTX (20 mg/kg i.p).
resultsAfter performing biochemical analysis, liver enzymes and malondialdehyde were significantly higher in the MTX group, indicating hepatic oxidative damage. MTX-induced OS was further confirmed with observation of events such as reactive oxygen species (ROS) overproduction, mitochondrial outer membrane potential decrease, mitochondrial swelling, cytochrome c release and caspase-3/9 increase, resulting in apoptosis. Furthermore, overexpression of pro-inflammatory factors such as nuclear factor kappa B (NF-ĸB) and interleukin 6 (IL-6) indicated the MTX-induced inflammation in MTX-treated group. Interestingly, EA was able to significantly prevent OS, mitochondrial dysfunction, apoptosis and inflammation induced by MTX. Also, EA-treated rats demonstrated significant upregulation of both nuclear factor erythroid 2-related factor 2 (Nrf2) and hemoxygenase-1 (HO-1), which were considerably downregulated in MTX-treated rats.
conclusionsEA protects rats against MTX-induced apoptosis and mitochondrial dysfunction via up-Regulating Nrf2 and HO-1 expression and inhibiting the NF-κB signaling pathway. Therefore, EA may protect patients against MTX-induced hepatotoxicity and encourage its clinical application. Graphical abstract Beneficial effect of Ellagic acid (EA) on Methotrexate (MTX)-induced liver injury: molecular mechanism.
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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.