ArticleToxics2023
Platelet Rich Plasma and Adipose-Derived Mesenchymal Stem Cells Mitigate Methotrexate-Induced Nephrotoxicity in Rat via Nrf2/Pparγ/HO-1 and NF-Κb/Keap1/Caspase-3 Signaling Pathways: Oxidative Stress and Apoptosis Interplay.
Article in Toxics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 20 citations in OpenAlex.
- L-Carnitine Attenuates Methotrexate-Induced Nephrotoxicity by Modulating BAX/BCL2 Apoptotic Signaling and Preserving Podocyte, Endothelial, and Tubular Integrity.Journal of applied toxicology : JAT · 2026Article
- Differential and Combined Therapeutic Effects of Mesenchymal Stem Cells and Glutathione on Methotrexate-Induced Mucositis.Journal of biochemical and molecular toxicology · 2026Article
- Human placental extract ameliorates methotrexate-induced nephrotoxicity in albino rats: ultrastructural, biochemical and biophysical studies.Scientific reports · 2026Article
- Effects of Chemotherapeutic Agents (5-Fluorouracil, Cisplatin and Methotrexate) on Cell Adhesion Molecules and Oxidative Damage Markers in Rat Kidney Tissue.Basic & clinical pharmacology & toxicology · 2026Article
- Article
- Activation of Nrf2 with natural flavonoids and mesenchymal stromal/stem cells: mechanisms and therapeutic potential for inflammatory diseases.Stem cell research & therapy · 2026Review
- Curcumin treatment attenuates methotrexate-induced nephrotoxicity in rats by inhibiting inflammation and fibrosis.Journal of molecular histology · 2026Article
- Platelet-rich plasma improves caspase-3 of skin graft treated with Tilapia Mozambique bio-dressing.Open veterinary journal · 2025Article
- Silica nanoparticles trigger striatal oxidative stress, apoptosis, and histopathological alterations: in vivo and in silico molecular docking insights.Histochemistry and cell biology · 2025Article
- Inflammatory Pathways to Carcinogenesis: Deciphering the Rheumatoid Arthritis-Lung Cancer Connection.Cancers · 2025Review
- A Retrospective Cohort Study Investigating the Effect of Intraovarian Platelet-Rich Plasma Therapy on the Oxidative State of Follicular Fluid in Women with Diminished Ovarian Reserve.Chonnam medical journal · 2025Article
- Correlation between oxidative stress level and clinical outcome in rotator cuff injury patients.American journal of translational research · 2025Article
- Exploring the protective mechanisms of the yunpi jiedu tongluo qushi decoction on methotrexate-induced reproductive damage in male rats based on Nrf2/HO-1 signaling pathway.Frontiers in cell and developmental biology · 2025Article
- Benzoylaconine Protects Skeletal Muscle Against Ischemia-Reperfusion Injury Through Activation of IF1-Dependent AMPK/Nrf2 Axis.Drug design, development and therapy · 2024Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundthe nephrotoxicity of methotrexate (MTX) is observed in high-dose therapy. Moreover, low-dose MTX therapy for rheumatic diseases is debatable and claimed to cause renal impairment. This study aimed at studying the effect of methotrexate in repeated low doses on rat kidneys and assessing the efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) and platelet rich plasma (PRP) for attenuating this effect.
methodsForty-two male Wistar rats were used, 10 rats were donors of AD-MSCs and PRP, 8 rats served as control, and the remaining rats were subjected to induction of nephrotoxicity by MTX intraperitoneal injection once weekly for successive 8 weeks and then assigned into 3 groups of 8 animals each: Group II: received MTX only. Group III: received MTX + PRP. Group IV: received MTX + AD-MSCs. After one month, rats were anaesthetized, serum-sampled, and renal tissue removed for biochemical, histological, and ultrastructural evaluation.
resultsthere was significant tubular degeneration, glomerulosclerosis, fibrosis, decreased renal index, along with increased levels of urea and creatinine in the MTX group compared to the control group. Immunohistochemical expression of caspase-3 and iNOS in the renal tissue was significantly increased in group II compared to groups III and IV. Biochemical results revealed higher tissue malondialdehyde (MDA) concentration in the MTX-injected group which decreased significantly in co-treatment with either AD-MSC or PRP + MTX. MSC promoted the activation of the Nrf2/PPARγ/HO-1 and NF-κB/Keap1/caspase-3 pathways, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. PRP showed therapeutic effects and molecular mechanisms similar to MSC. Furthermore, MSC and PRP treatment significantly reduced MTX-induced upregulation of the pro-inflammatory (NF-κB, interleukin-1ß, and TNF-α), oxidative stress (Nrf-2, hemoxygenase-1, glutathione, and malondialdehyde), and nitrosative stress (iNOS) markers in the kidney.
conclusionrepeated administration of low-dose MTX resulted in massive renal tissue toxicity and deterioration of renal function in rats which proved to be attenuated by PRP and AD-MSCs through their anti-inflammatory, anti-apoptotic and anti-fibrotic properties.
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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 Socratic graph.