ArticleNaunyn-Schmiedeberg's archives of pharmacology2026
Apremilast ameliorates methotrexate-induced renal injury in rats: role of TLR4/NF-κB/P38 MAPK/caspase-3 and Nrf2/HO-1 signaling pathways.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Olmesartan-Loaded PLGA Nanoparticles Attenuate Methotrexate-Induced Kidney Injury: Association with the AT1R/ERK1/2 Signaling Axis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Imeglimin halts cyclophosphamide-induced ovarian injury: a dual modulation of TLR4/NF-κB/NLRP3-driven inflammation and AMPK/SIRT1/PGC-1α pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Sacubitril/valsartan attenuates renal injury caused by cecal ligation and puncture via TLR4/NFκB/NLRP3 inhibition and reduced oxidative stress and apoptosis in rats.Scientific reports · 2026Article
- Yiqi Huoxue Jiedu formula protects against sepsis-associated lung injury by modulating macrophage mitophagy and mtDNA-STING signaling.Chinese medicine · 2026Article
- Current perspectives on natural and pharmacological interventions for combating drug-induced pulmonary toxicity.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Naringenin Attenuates Methotrexate-Induced Nephrotoxicity Accompanied by Alterations in Oxidative Stress, Inflammatory, Apoptotic, and Endoplasmic Reticulum Stress Responses.International journal of molecular sciences · 2026Article
- Renoprotective effects of vitamin D and thymoquinone, alone and in combination, in a rat co-treatment model of gentamicin-induced acute kidney injury.Molecular and cellular biochemistry · 2026Article
- Atomoxetine attenuates methotrexate-induced lung injury in rats implicating TLR4/NF-κB and Bax/Bcl-2/caspase-3 signaling cascades: a study based on molecular docking and experimental validation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- HIPK2 mediated regulation of ferroptosis and inflammatory signaling in sepsis-induced myocardial injury.Journal of molecular histology · 2026Article
- Karacoline attenuates sepsis-induced acute lung injury by suppressing apoptosis via PPARγ-associated inhibition of JNK/ERK MAPK signaling.Respiratory research · 2026Article
- Liposomal Piceatannol Mitigates Methotrexate-Induced Oxidative Renal Injury via Modulation of Nrf2/HO-1, TLR4/NF-κB, MAPK, and Apoptotic Pathways in Rats.Biomolecules · 2026Article
- Silencing TMED2 suppresses cell growth and tumor progression in diffuse large B-cell lymphoma via inducing G0/G1 cell cycle arrest.Frontiers in oncology · 2026Article
- Involvement of NOD1/NF-κB/MAPK pathway in the protective effect of procyanidin B2 against methotrexate-induced nephrotoxicity.Science progressArticle
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Authors and funding
6 authors.
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Abstract
This study aimed to assess the preventive potential of apremilast (APRE) against methotrexate (MTX)-induced renal damage in rats through modulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling and toll-like receptor 4/nuclear factor-kappa B/p38 mitogen-activated protein kinase/caspase-3 (TLR4/NF-κB/p38 MAPK/Caspase-3) signaling pathways. Four groups of male Wistar albino rats were assigned: control, APRE, MTX, MTX + APRE. Histopathological investigation and biochemical analysis of the serum renal damage indicators (urea and creatinine) were used to evaluate the renal toxicity of MTX. Testing for renal malondialdehyde (MDA) and reduced glutathione (GSH) was conducted. The levels of renal tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), Nrf2, HO-1, and cleaved caspase-3 were measured using the ELISA method. Using an immunohistochemistry method, the expression of NF-κB p65 in the kidney was investigated. Western blotting was used to examine the expression of TLR4 and p38 MAPK proteins. MTX administration resulted in significant renal injury, as evidenced by elevated serum urea and creatinine levels. The kidneys were significantly affected as evidenced by histopathological alterations and increased levels of renal MDA, TNF-α, IL-6, Bcl-2-associated x (Bax), and cleaved caspase-3, alongside decreased levels of GSH and B-cell lymphoma 2 (Bcl-2) expression. These outcomes were linked to inhibition of Nrf2/HO-1 signaling and activation of the TLR4/NF-κB/p38 MAPK/Caspase-3 pathway. Co-treatment with APRE at 20 mg/kg/day for 21 days markedly improved all biochemical and pathological alterations evoked by MTX, demonstrating significant nephroprotective effects. Apremilast inhibits methotrexate's harmful effects on the kidneys by activating signaling cascades that include Nrf2/HO-1, while simultaneously downregulating TLR4/NF-κB/p38 MAPK/Caspase-3.
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