Deferoxamine Research Articles

Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. In this study, it is found that senescent bone marrow mesenchymal stem cells (BMSCs) exhibit increased sensitivity to ferroptosis, a phenomenon associated with Steap4, a nicotinamide adenine dinucleotide phosphate hydrogen (NADPH)-dependent metalloreductase that reduces Fe3+ to Fe2+. Therefore, it is aimed to innovatively elucidate how Steap4 affects ferroptosis in senescent BMSCs. These findings indicate that Steap4 promotes intracellular Fe2+ accumulation and elevates reactive oxygen species (ROS) levels, collectively driving the upregulation of CCAAT/enhancer binding protein beta (C/EBPβ) expression. Interestingly, a functional C/EBPβ binding site is identified within the Steap4 promoter region. Mechanistically, knockdown studies demonstrated that C/EBPβ depletion attenuated Steap4 expression, whereas C/EBPβ overexpression conversely upregulated Steap4 levels. These regulatory processes establish a self-amplifying Steap4/Fe2+-ROS/C/EBPβ positive feedback loop. Notably, a large number of adipocytes are also observed in the bone marrow of aged mice. Knockdown of Steap4 and C/EBPβ suppressed the differentiation of BMSCs into adipocytes. Knockdown of Steap4 or deferoxamine (DFO) treatment in animal experiments effectively relieves SOP. In conclusion, Steap4 accelerates the onset of ferroptosis in senescent BMSCs and promotes their differentiation to adipocytes through the Steap4/Fe2+-ROS/C/EBPβ axis, ultimately impairing their osteogenic capacity.

Deferoxamine attenuates sepsis-induced liver injury by suppressing ferroptosis.

Ferroptosis contributing to spermatocyte injury induced by silica nanoparticles via BRCA1/GPX4 signaling.

NFE2L2 protects against Sorafenib-induced Ferroptosis and cardiotoxicity by activating the HO1/ferritin pathway.

VIRMA utilizes m6A-IGF2BP2 to mediate NDRG1, thereby increasing sensitivity to iron-chelating agents and subsequently inhibiting the proliferation and metastasis of oral squamous cell carcinoma.

Macular laser for diabetic macular edema (DME) is known to increase heat shock protein (HSP) expression in retinal pigment epithelial (RPE) cells, and increased HSP expression may be a mechanism for improving macular edema. Furthermore, the effectiveness of mild electrical stimulation (MES) as a cofactor in further enhancing HSP expression by thermal stimulation has been reported. In the current study, the effect of this combination treatment was examined in an in vitro HG (high glucose) + DFX (deferoxamine mesylate salt) model that simulates DME using a human RPE cell line (ARPE-19). Combined thermal stimulation and MES significantly increased HSP70 expression in both the control and HG + DFX model groups, while suppressing VEGF and inflammatory cytokine levels in HG + DFX model. The combined treatment also showed a protective effect on the blood-retinal barrier integrity, although transient, as measured by TEER. These findings suggest that combined thermal stimulation and MES represent a promising therapeutic approach for managing DME, by modulating HSP and VEGF expression and potentially reducing inflammation and promoting protective mechanisms in the retina.

Desferrioxamine (DFO) is a clinically established iron chelator used to manage iron overload in transfusion-dependent thalassemia patients. Despite its efficacy, DFO's poor cellular permeability and burst release profile limit its application to subcutaneous administration, precluding its use as an oral formulation. To address these limitations, DFO was encapsulated in a nanocomposite matrix composed of chitosan (CTS), polyethylene oxide (PEO), ethyl cellulose (EC), and tripolyphosphate (TPP). The resulting nanocomposites were comprehensively characterized using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), particle size analysis (PSA), and Fourier-transform infrared spectroscopy (FT-IR). The in vitro evaluation assessed drug release behavior at physiological pH, intestinal pH, and cellular uptake in HeLa cell lines. Among the tested formulations, DFO_PEO_EC_CTS_TPP_1 exhibited the highest drug loading capacity (285.56 ± 0.04 mg g−1), entrapment efficiency (85.67 ± 13.35%), and antioxidant activity. Drug release kinetics were best described by the Peppas–Sahlin model (R2 = 0.9999), indicating a Case II relaxation-controlled mechanism, supporting a sustained release profile. Blood compatibility was confirmed through Wilks' Lambda test, comparing coagulation parameters (APTT, PT) and complement levels (C3) between control and treated samples, including Fe(iii)-DFO_PEO_EC_CTS_TPP_1 at 0.5 mg mL−1 and 37 °C. No statistically significant differences were observed (e.g., PT, p = 0.052), confirming the hemocompatibility of the formulation. The MTT cytotoxicity assay for the optimal formulation yielded an IC50 value of 29.9 ± 5 μM, indicating acceptable cytocompatibility. Furthermore, the formulation demonstrated enhanced DFO permeability across cell membranes and sustained drug release over time. In conclusion, encapsulation of DFO within the PEO_EC_CTS_TPP nanocomposite matrix presents a promising strategy to overcome the limitations of native DFO, offering improved cell permeability, biocompatibility, and controlled release, potentially advancing it toward more effective therapeutic applications.

Dynamic Schiff-base cross-linked hydrogel deferoxamine-loaded microspheres for microenvironment-responsive drug release to promote chronic diabetic wound healing.

Inhibition of the 4-hydroxynonenal-regulated JNK/c-Jun pathway improves bleomycin-induced lung fibrosis.

Arsenic trioxide enhances the inhibitory effect of lenvatinib on hepatocellular carcinoma through HMOX1-mediated ferroptosis.

Microalgae-MOF integrated drug delivery system for cranial radiotherapy and chemotherapy-induced brain injury.

Abstract Widespread human exposure to aluminum (Al) has raised increasing concerns about its effects on neuronal functions since Al3+ can cross the blood–brain barrier and accumulate in neuronal cells, especially considering its ionic similarity to ferric iron (Fe3+), a metal strongly associated with neurodegenerative diseases. In this study, we demonstrate that Al3+ affects vesicles in an iron‐status‐dependent manner in pheochromocytoma (PC12) cells, causing distinct changes under iron‐normal, deficient, and overloaded conditions. Al3+ competes with Fe3+ for transferrin binding and enters cells via transferrin receptor (TfR)‐mediated endocytosis, ultimately leading to cellular iron deficiency. This disruption alters dopamine‐related proteins and molecular pathways, impairing exocytotic dynamics and reducing the average vesicular transmitter storage. When iron level is overloaded, TfR expression is downregulated to avoid Al3+ affecting vesicles. However, supplementation with ferric ammonium citrate (FAC) fails to reverse Al3+‐induced iron deficiency due to Al3+ simultaneously upregulating TfR, allowing excess Fe3+ to further decrease neurotransmitter release. Furthermore, deferoxamine (DFOM), an Fe chelator, destabilizes exocytotic fusion pores, suggesting a potential drawback of chelation therapy. These findings highlight iron dysregulation as a key pathway through which Al3+ impairs vesicular function, providing a new insight into how metal ion interactions modulate neurotransmission.

Widespread human exposure to aluminum (Al) has raised increasing concerns about its effects on neuronal functions since Al3+ can cross the blood-brain barrier and accumulate in neuronal cells, especially considering its ionic similarity to ferric iron (Fe3+), a metal strongly associated with neurodegenerative diseases. In this study, we demonstrate that Al3+ affects vesicles in an iron-status-dependent manner in pheochromocytoma (PC12) cells, causing distinct changes under iron-normal, deficient, and overloaded conditions. Al3+ competes with Fe3+ for transferrin binding and enters cells via transferrin receptor (TfR)-mediated endocytosis, ultimately leading to cellular iron deficiency. This disruption alters dopamine-related proteins and molecular pathways, impairing exocytotic dynamics and reducing the average vesicular transmitter storage. When iron level is overloaded, TfR expression is downregulated to avoid Al3+ affecting vesicles. However, supplementation with ferric ammonium citrate (FAC) fails to reverse Al3+-induced iron deficiency due to Al3+ simultaneously upregulating TfR, allowing excess Fe3+ to further decrease neurotransmitter release. Furthermore, deferoxamine (DFOM), an Fe chelator, destabilizes exocytotic fusion pores, suggesting a potential drawback of chelation therapy. These findings highlight iron dysregulation as a key pathway through which Al3+ impairs vesicular function, providing a new insight into how metal ion interactions modulate neurotransmission.

(1) Background: The extracellular matrix (ECM) is a natural scaffold for cells, creating a three-dimensional architecture composed of fibrous proteins (mainly collagen) and proteoglycans, which are synthesized by resident cells. In this study, a physiological hypoxic environment was utilized to enhance ECM production by human mesenchymal stem cells (hMSCs), a process relevant to tissue engineering and regenerative medicine. (2) Methods: hMSCs were treated with deferoxamine (DFO), a pharmaceutical hypoxia-mimetic agent that induces cellular responses similar to low-oxygen conditions through stabilization of hypoxia inducible factor-1α (HIF-1α). The time points 0 h 24 h, 3 h 24 h, and 24 h 24 h refer to DFO being added immediately after cell seeding (before cells adhesion), 3 h after cell seeding (during initial cells attachment), and 24 h after cell seeding (after focal adhesions formation and actin organization), respectively, to evaluate the influence of cell adhesion on ECM deposition. hMSCs incubated in culture media were subsequently exposed to DFO for 24 h. Samples were then subjected to cell viability tests, scanning electron microscopy (SEM), atomic force microscopy (AFM) and laser scanning confocal microscopy (CLSM) assessments. (3) Results: Viability tests indicated that DFO concentrations in the range of 0–300 µM were non-toxic over 24 h. The presence of collagen fibers in the DFO-derived ECM was confirmed with anti-collagen antibodies under CLSM. Increased ECM secretion was observed under the following conditions: 3 μM DFO (24 h 24 h), 100 μM DFO (0 h 24 h) and 300 μM DFO (3 h 24 h). SEM and AFM images revealed the morphology of various stages of collagen formation with both collagen fibrils and fibers identified. (4) Conclusions: Our preliminary study demonstrated enhanced ECM secretion by hMSC treated with DFO at concentrations of 3, 100, and 300 µM within a short cultivation period of 24–48 h without significant affecting cell viability. By mimicking physiological processes, it may be possible to stimulate endogenous tissue regeneration, for example, at an injury site.

Endothelial‐derived reactive oxygen species (ROS), modulated by free iron levels, are key drivers of neutrophil extracellular traps (NETs) formation and contribute to cerebral ischemia/reperfusion (CI/R) injury. Targeting ROS and iron could possibly reduce NETs formation and mitigate stroke. NETs were predominantly initiated by hypoxia/reoxygenation (H/R) in endothelial cells (ECs), rather than in neutrophils. Silencing Fpn1 in ECs significantly reduced extracellular iron, suppressed ROS production, and inhibited NETs formation—effects that were reversed by supplementation with iron or hemin. Additionally, both vitamin C (Vc) and deferoxamine (DFOM) suppressed blood coagulation on Fpn1‐silenced ECs under H/R conditions. NETs formation on hypoxic ECs was further enhanced in the presence of co‐cultured red blood cells. In a mouse model of middle cerebral artery occlusion, combined treatment with Vc and DFOM synergistically reduced infarct size. Although Vc or DFOM alone reduced NETs formation, their combined use showed a weaker effect than DFOM alone, possibly because better blood flow increased neutrophil contact with the endothelium. In conclusion, endothelial ROS and iron play critical roles in regulating NETs formation during CI/R injury. Combined treatment with Vc and DFOM offers a promising therapeutic strategy to reduce stroke‐induced damage by modulating ROS levels and NETs formation.

Immune cell response after intracerebral hemorrhage in piglets and the treatment effects of deferoxamine and minocycline.

Bioinspired hierarchical fiber-hydrogel dressing with dual immunomodulatory and angiogenic functions for diabetic wound healing.

Iron dysregulation and ferroptosis are associated with pulmonary fibrosis: Insight from idiopathic pulmonary fibrosis, systemic sclerosis, and COVID-19 patients.

Unveiling tectorigenin: A novel ferroptosis inducer targeting EGFR in bladder cancer.

NCOA4-dependent ferritinophagy drives perfluorooctanoic acid-triggered renal ferroptosis in chicken embryos.