ArticleScientific reports2017
Deferasirox-induced iron depletion promotes BclxL downregulation and death of proximal tubular cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Remdesivir nephrotoxicity in tubular epithelial cells.Frontiers in pharmacology · 2026Article
- Natural flavonoids from herbs and nutraceuticals as ferroptosis inhibitors in central nervous system diseases: current preclinical evidence and future perspectives.Frontiers in pharmacology · 2025Review
- Deferasirox's Anti-Chemoresistance and Anti-Metastatic Effect on Non-Small Cell Lung Carcinoma.Biomedicines · 2024Article
- Bibliometric analysis of ferroptosis in acute kidney injury from 2014 to 2022.International urology and nephrology · 2023Article
- Regulated cell death pathways in kidney disease.Nature reviews. Nephrology · 2023Review
- ATF4-activated parkin induction contributes to deferasirox-mediated cytoprotection in Parkinson's disease.Toxicological research · 2023Article
- Kidney tubule iron loading in experimental focal segmental glomerulosclerosis.Scientific reports · 2022Article
- Iron status influences the response of cord blood megakaryocyte progenitors to eltrombopag in vitro.Blood advances · 2022Article
- Renal function in β-thalassemia major patients treated with two different iron-chelation regimes.BMC nephrology · 2021Article
- Assessment of Subclinical Renal Glomerular and Tubular Dysfunction in Children with Beta Thalassemia Major.Children (Basel, Switzerland) · 2021Article
- Fabrication of deferasirox-decorated aptamer-targeted superparamagnetic iron oxide nanoparticles (SPION) as a therapeutic and magnetic resonance imaging agent in cancer therapy.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2021Article
- Article
- Molecular pathways driving omeprazole nephrotoxicity.Redox biology · 2020Article
- The multifaceted role of iron in renal health and disease.Nature reviews. Nephrology · 2020Review
- The iron chelator Deferasirox causes severe mitochondrial swelling without depolarization due to a specific effect on inner membrane permeability.Scientific reports · 2020Article
- Early Kidney Damage Markers after Deferasirox Treatment in Patients with Thalassemia Major: A Case-Control Study.Oxidative medicine and cellular longevity · 2019Article
- Cell death-based approaches in treatment of the urinary tract-associated diseases: a fight for survival in the killing fields.Cell death & disease · 2018Review
- Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron deficiency has been associated with kidney injury. Deferasirox is an oral iron chelator used to treat blood transfusion-related iron overload. Nephrotoxicity is the most serious and common adverse effect of deferasirox and may present as an acute or chronic kidney disease. However, scarce data are available on the molecular mechanisms of nephrotoxicity. We explored the therapeutic modulation of deferasirox-induced proximal tubular cell death in culture. Deferasirox induced dose-dependent tubular cell death and AnexxinV/7AAD staining showed features of apoptosis and necrosis. However, despite inhibiting caspase-3 activation, the pan-caspase inhibitor zVAD-fmk failed to prevent deferasirox-induced cell death. Moreover, zVAD increased deferasirox-induced cell death, a feature sometimes found in necroptosis. Electron microscopy identified mitochondrial injury and features of necrosis. However, neither necrostatin-1 nor RIP3 knockdown prevented deferasirox-induced cell death. Deferasirox caused BclxL depletion and BclxL overexpression was protective. Preventing iron depletion protected from BclxL downregulation and deferasirox cytotoxicity. In conclusion, deferasirox promoted iron depletion-dependent cell death characterized by BclxL downregulation. BclxL overexpression was protective, suggesting a role for BclxL downregulation in iron depletion-induced cell death. This information may be used to develop novel nephroprotective strategies. Furthermore, it supports the concept that monitoring kidney tissue iron depletion may decrease the risk of deferasirox nephrotoxicity.
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