ArticleDrug design, development and therapy2024
The Protective Effect of Roflumilast Against Acute Hepatotoxicity Caused by Methotrexate in Wistar Rats: In vivo Evaluation.
Article in Drug design, development and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Comparative hepatoprotective effects of Ginkgo biloba extract and N-Acetylcysteine against methotrexate-induced liver injury in rats: modulation of IκB-α, p38 MAPK, and p53 phosphorylation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Formulation and characterization of escin loaded-chitosan nanoparticles and assessment of its anti-arthritic potential in Wistar rats: a mechanistic approach.Inflammopharmacology · 2026Article
- Pharmacological Mechanisms of Phytochemicals and Pharmaceutical Agents in Protecting Against Methotrexate-Induced Liver Injury.Oxidative medicine and cellular longevity · 2026Review
- In vivo and in silico studies on the potential role of garden cress oil in attenuating methotrexate-induced inflammation and apoptosis in liver.Scientific reports · 2025Article
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Abstract
Introduction: Methotrexate (MTX) is one of the most widely used drugs in cancer chemotherapy and treating rheumatoid arthritis. The hepatotoxicity of MTX is one of its major side effects. Roflumilast (ROF) has been recognized to have antioxidant and anti-inflammatory activity in in-vivo and in-vitro models. The present study aimed to explore the potential protective effects of roflumilast against MTX-induced liver toxicity in male Wistar rats. Methods: High dose of 5 mg/kg for 4 consecutive days subcutaneous (S.C) injection of methotrexate for induction of acute liver injury. A total of 24 Wistar rats, rats were used in four different groups. The NS injections were given S.C to the control group once a day for 4 consecutive days. SC injections of MTX (5 mg/kg) were given to the MTX group daily for four days. At 5 mg/kg once daily for four days, the roflumilast group was given daily oral roflumilast. An injection of MTX and oral roflumilast were given to the MTX + roflumilast group once daily for four consecutive days. Results: Administration of high dose MTX (5 mg/kg) today 4 produced a significant decrease in hepatic glutathione (GSH) levels and a significant increase in ALT and AST liver enzymes, hepatic malondialdehyde (MDA), tumor suppressor protein (p53), interleukin 6, interleukin 1 levels compared to the control group. Treatment with roflumilast for 4 days significantly attenuated unfavorable changes in these parameters. According to histopathological findings, Roflumilast significantly reduced MTX-induced inflammation and degeneration in the liver. In conclusion, the findings indicate that roflumilast may have a potential therapeutic benefit in treating rats with MTX-induced liver toxicity by mitigating its effects. Purpose: The aim of this study is to investigate the potential protective effects of roflumilast against MTX-induced liver toxicity in Wistar rats.
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