ArticleMolecular biology reports2024
Melatonin mitigated methotrexate-induced hepatotoxicity through interrelated biological processes.
Article in Molecular biology reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Protective Effects of Lactobacillus rhamnosus GG Against Methotrexate-Induced Oxidative Renal Toxicity.Probiotics and antimicrobial proteins · 2026Article
- Fondaparinux attenuates methotrexate-induced hepatotoxicity by regulating coagulation, endothelial dysfunction, and inflammatory signaling via the TLR4/NLRP3 and NF-κB/IL-1β/MCP-1 pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Pharmacological Mechanisms of Phytochemicals and Pharmaceutical Agents in Protecting Against Methotrexate-Induced Liver Injury.Oxidative medicine and cellular longevity · 2026Review
- Therapeutic and chemopreventive potential of melatonin in liver diseases: targeting oxidative stress and inflammatory signaling.Frontiers in pharmacology · 2026Review
- Balancing efficacy and hepatotoxicity: a comprehensive review of oral medications in psoriasis management.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Pyridostigmine Mitigates Methotrexate-Induced Liver Fibrosis in Rats: Association with Changes in BMP-9, SIRT1, and Endoglin Expression.Biomedicines · 2025Article
- Repositioning Perindopril for Mitigation of Methotrexate-Induced Hepatotoxicity in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
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Authors and funding
5 authors.
Funding
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Abstract
backgroundHepatotoxicity associated with methotrexate (MTX) is mainly due to disruption of redox balance and development of oxidative injury to hepatocytes. Melatonin (MLT) is a potent antioxidant and regulates wide range of biological functions, processes and utilized as adjuvant for number of medical applications. The current study investigated the mitigating effect of MLT on the MTX-induced hepatotoxicity. METHODS AND
resultsAdult male rats received MLT (25 mg/kg, orally) for seven days flowed by single injection of MTX (20 mg/kg, ip) then treat with MLT continued for additional 7 days. The present result showed MLT treatment mitigated histopathological changes in the liver that associated with normalization of ALT and AST activity as well as bilirubin, albumin and alfa-fetoprotein levels in serum of MLT + MTX-treated rat to comparable control level. MLT treatment significantly reduced MDA content and myeloperoxidase activity while enhanced the activity of superoxide dismutase, catalase and glutathione content in the liver indicating the empowerment of the antioxidant status. Amelioration of MLT-induced oxidative stress resulted in a reduction in the inflammatory response due to antioxidant restoration and inhibited apoptosis indicated by downregulation of caspase-3 expression. The replenishment of antioxidant content powers the defense system of the hepatocytes. As a result, apoptosis is reduced which might be due to the ability of MLT protect DNA integrity thus maintaining hepatocyte functions and structure. Consequently, liver histology was protected.
conclusionsIn summary, MLT modulates liver function and structure by orchestrating linked processes, including redox balance, inflammatory response, suppression of caspase-3, and DNA damage.
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Registered trials
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