ArticleBiomolecules & therapeutics2023
Synergistic Renoprotective Effect of Melatonin and Zileuton by Inhibition of Ferroptosis
Article in Biomolecules & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Breaking the cycle of fibrosis: Ferroptosis as a therapeutic target (Review).International journal of molecular medicine · 2026Review
- Quercetin Alleviates Ferroptosis-Induced Renal Fibrosis by Modulating the PRDM9/HMOX1/PTGS2 Axis.ACS omega · 2026Article
- Integrating TWAS, chemical-genomic networks, and experimental models: melatonin as a ferroptosis inhibitor in osteoarthritis therapy.Clinical rheumatology · 2026Article
- Navigating the New Therapeutic Landscape: Innovative Strategies for Overcoming Resistance and Degeneration.Biomolecules & therapeutics · 2026Article
- Ferroptosis and Alzheimer's disease: unraveling the molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Therapy-Induced Senescence (TIS) and SASP: The p53-Mediated Interplay in Cancer Progression and Treatment.International journal of molecular sciences · 2025Review
- Exploration of zileuton protective mechanisms against vancomycin-associated nephrotoxicity.Toxicology and applied pharmacology · 2025Article
- Synergistic effects of AgNPs and zileuton on PCOS via ferroptosis and inflammation mitigation.Redox report : communications in free radical research · 2025Article
- Ferroptosis and renal fibrosis: mechanistic insights and emerging therapeutic targets.Renal failure · 2025Review
- The role of ferroptosis in acute kidney injury: the preemptive mode of cell death and the bridging effect.Renal failure · 2025Review
- Renoprotective Effects of MIT-001 in Ischemia-Reperfusion Injury: Modulation of Ferroptosis, ROS and Fibrotic Markers.Journal of cellular and molecular medicine · 2025Article
- Zileuton Attenuates Acute Kidney Injury in Glycerol-Induced Rhabdomyolysis by Regulating Myeloid-Derived Suppressor Cells in Mice.International journal of molecular sciences · 2025Article
- Drug development studies supporting zileuton as a parenteral adjuvant to attenuate antibiotic-associated nephrotoxicity.Antimicrobial agents and chemotherapy · 2025Article
- NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Melatonin Activates KEAP1/NRF2/PTGS2 Pathway to Attenuate Hyperoxia-Driven Ferroptosis in Bronchopulmonary Dysplasia.Journal of inflammation research · 2025Article
- Emerging and Promising Keywords in Biomolecules and Therapeutics for 21st Century Diseases.Biomolecules & therapeutics · 2025Article
- Cathepsin B induces kidney diseases through different types of programmed cell death.Frontiers in immunology · 2025Review
- Unraveling Ferroptosis: A New Frontier in Combating Renal Fibrosis and CKD Progression.Biology · 2024Review
- Metal-Dependent Cell Death in Renal Fibrosis: Now and in the Future.International journal of molecular sciences · 2024Review
- The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside.Clinical and experimental medicine · 2024Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.
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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.