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Seminars in Hematology Jan 2001Despite the clinical use of deferoxamine for more than a quarter of a century, pharmacokinetic studies are few and have not been performed explicitly in patients with... (Comparative Study)
Comparative Study Review
Despite the clinical use of deferoxamine for more than a quarter of a century, pharmacokinetic studies are few and have not been performed explicitly in patients with sickle cell disorders. Early studies with Intravenous administration to healthy volunteers and patients with transfusional overload showed that although peak concentrations of deferoxamine were similar in both groups, concentrations of ferrioxamine were higher in the latter. In iron-overloaded patients with hereditary hemochromatosis, an intramuscular 10 mg/kg bolus of deferoxamine gave maximal plasma ferrioxamine concentrations exceeding those of deferoxamine, whereas in normal controls the reverse was the case. In more recent studies with homozygous beta-thalassemia, using continuous Intravenous deferoxamine infusion at 50 mg/kg/d, and initial elimination half-life of 0.28/h and steady-state concentration of 7 micromol/L were observed. In these studies, steady-state plasma levels of the predominant deferoxamine metabolite B were usually lower than those of unmetabolized deferoxamine. In a further intravenous infusion study, the proportion of plasma metabolites was higher in those thalassaemia patients with low serum ferritin levels relative to their current mean daily deferoxamine dose, suggesting that high metabolite levels may predict excessive desferrioxamine dosing. This hypothesis is supported by subcutaneous studies in which low doses of slow-release depot deferoxamine resulted in significantly lower proportions of plasma metabolites than with conventional 8-hour infusions at 40 mg/kg. Because serum ferritin is particularly unreliable as a marker of iron overload in sickle cell disorders, measurement of metabolites or the relative proportions of deferoxamine and ferrloxamine may help identify patients at risk of excessive dosing. Because iron overload is likely to become an increasing issue in patients with sickle cell disorders, studies of the pharmacokinetics and metabolism of deferoxamine in this patient group are needed.
Topics: Anemia, Sickle Cell; Deferoxamine; Drug Administration Routes; Ferric Compounds; Humans; Iron Chelating Agents; Kinetics
PubMed: 11206963
DOI: 10.1016/s0037-1963(01)90061-7 -
PloS One 2018Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Several recent controlled trials have reported that deferoxamine (DFX)... (Review)
Review
Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Several recent controlled trials have reported that deferoxamine (DFX) therapy appears to be effective for ICH. The aim of this study was to perform a systematic review of DFX therapy for ICH patients and evaluate the efficacy and safety of DFX therapy for ICH patients. We searched Medline, Embase, the Cochrane Database of Systematic Reviews, clinicaltrials.gov, all Chinese databases and the reference lists of all included studies and review articles. We then performed a systematic review of studies involving the administration of DFX following ICH. Only two studies were included, a prospective, randomized clinical trial and a prospective,observational cohort study with concurrent groups. Qualitative analysis of each study revealed one randomized controlled trial of moderate quality with a moderate risk of bias and one observational cohort study of moderate quality with a moderate risk of bias. DFX may be an effective treatment for edema in patients with ICH. However, due to the small number of trials and small sample sizes of these trials, insufficient evidence exists to determine the effect of DFX on neurologic outcomes after ICH and the safety of this intervention. Further investigation is required before DFX can become a routine treatment for ICH.
Topics: Cerebral Hemorrhage; Deferoxamine; Humans
PubMed: 29566000
DOI: 10.1371/journal.pone.0193615 -
Advances in Wound Care Oct 2022By 2030, there will be >4 million radiation-treated cancer survivors living in the United States. Irradiation triggers inflammation, fibroblast activation, and...
By 2030, there will be >4 million radiation-treated cancer survivors living in the United States. Irradiation triggers inflammation, fibroblast activation, and extracellular matrix deposition in addition to reactive oxygen species generation, leading to a chronic inflammatory response. Radiation-induced fibrosis (RIF) is a progressive pathology resulting in skin pigmentation, reduced elasticity, ulceration and dermal thickening, cosmetic deformity, pain, and the need for reconstructive surgery. Deferoxamine (DFO) is a U.S. Food and Drug Administration (FDA)-approved iron chelator for blood dyscrasia management, which has been found to be proangiogenic, to decrease free radical formation, and reduce cell death. DFO has shown great promise in the treatment and prophylaxis of RIF in preclinical studies. Systemic DFO has a short half-life and is cumbersome to deliver to patients intravenously. Transdermal DFO delivery is complicated by its high atomic mass and hydrophilicity, preventing stratum corneum penetration. A transdermal drug delivery system was developed to address these challenges, in addition to a strategy for topical administration. DFO has great potential to translate from bench to bedside. An important step in translation of DFO for RIF prophylaxis is to ensure that DFO treatment does not affect the efficacy of radiation therapy. Furthermore, after an initial plethora of studies reporting DFO treatment by intravenous and subcutaneous routes, a significant advantage of recent studies is the success of transdermal and topical delivery. Given the strong foundation of basic scientific research supporting the use of DFO treatment on RIF, clinicians will be closely following the results of the ongoing human studies.
Topics: Administration, Cutaneous; Administration, Topical; Chelating Agents; Deferoxamine; Fibrosis; Humans
PubMed: 34074152
DOI: 10.1089/wound.2021.0021 -
The American Journal of Pediatric... 1990Deferoxamine has been extensively used as chelation therapy in iron-overloaded states. Recently, some investigators have explored the potential usefulness of... (Review)
Review
Deferoxamine has been extensively used as chelation therapy in iron-overloaded states. Recently, some investigators have explored the potential usefulness of deferoxamine as an antiproliferative, antiinflammatory, and immunosuppressive agent. The studies of deferoxamine have indicated that the drug blocks DNA synthesis by inhibition of ribonucleotide reductase. Deferoxamine has also shown antiinflammatory properties, possibly by inhibition of polymorphonuclear neutrophil function. Analysis of possible antiinflammatory effects of deferoxamine has been complicated by concomitant immunosuppressive effects of the drug. Deferoxamine inhibits T lymphocyte proliferation, both by ribonucleotide reductase inhibition and by preventing the expression of interleukin 2 receptor-alpha chain. The use of iron-chelating agents in non-iron-overloaded patients carries the risk of neurologic, metabolic, and infectious complications. The clinical usefulness of deferoxamine in these novel applications will require careful study of both efficacy and any toxic effects.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Cell Division; Deferoxamine; Humans; Immunosuppressive Agents; Opportunistic Infections; Ribonucleotide Reductases
PubMed: 2178461
DOI: 10.1097/00043426-199021000-00003 -
Brain Research Aug 2023Traumatic brain injury (TBI) is an important reason of neurological damage and has high morbidity and mortality rates. The secondary damage caused by TBI leads to a poor...
Traumatic brain injury (TBI) is an important reason of neurological damage and has high morbidity and mortality rates. The secondary damage caused by TBI leads to a poor clinical prognosis. According to the literature, TBI leads to ferrous iron aggregation at the site of trauma and may be a key factor in secondary injury. Deferoxamine (DFO), which is an iron chelator, has been shown to inhibit neuron degeneration; however, the role of DFO in TBI is unclear. The purpose of this study was to explore whether DFO can ameliorate TBI by inhibiting ferroptosis and neuroinflammation. Here, our findings suggest that DFO can reduce the accumulation of iron, lipid peroxides, and reactive oxygen species (ROS) and modulate the expression of ferroptosis-related indicators. Moreover, DFO may reduce NLRP3 activation via the ROS/NF-κB pathway, modulate microglial polarization, reduce neutrophil and macrophage infiltration, and inhibit the release of inflammatory factors after TBI. Additionally, DFO may reduce the activation of neurotoxic responsive astrocytes. Finally, we demonstrated that DFO can protect motor memory function, reduce edema and improve peripheral blood perfusion at the site of trauma in mice with TBI, as shown by behavioral experiments such as the Morris water maze test, cortical blood perfusion assessment and animal MRI. In conclusion, DFO ameliorates TBI by reducing iron accumulation to alleviate ferroptosis and neuroinflammation, and these findings provide a new therapeutic perspective for TBI.
Topics: Mice; Animals; Deferoxamine; Neuroinflammatory Diseases; Reactive Oxygen Species; Ferroptosis; Brain Injuries, Traumatic; Iron
PubMed: 37149247
DOI: 10.1016/j.brainres.2023.148383 -
Molecules (Basel, Switzerland) Apr 2024Deferoxamine, an iron chelator used to treat diseases caused by excess iron, has had a Food and Drug Administration-approved status for many years. A large number of... (Review)
Review
Deferoxamine, an iron chelator used to treat diseases caused by excess iron, has had a Food and Drug Administration-approved status for many years. A large number of studies have confirmed that deferoxamine can reduce inflammatory response and promote angiogenesis. Blood vessels play a crucial role in sustaining vital life by facilitating the delivery of immune cells, oxygen, and nutrients, as well as eliminating waste products generated during cellular metabolism. Dysfunction in blood vessels may contribute significantly to the development of life-threatening diseases. Anti-angiogenesis therapy and pro-angiogenesis/angiogenesis strategies have been frequently recommended for various diseases. Herein, we describe the mechanism by which deferoxamine promotes angiogenesis and summarize its application in chronic wounds, bone repair, and diseases of the respiratory system. Furthermore, we discuss the drug delivery system of deferoxamine for treating various diseases, providing constructive ideas and inspiration for the development of new treatment strategies.
Topics: Deferoxamine; Humans; Animals; Neovascularization, Physiologic; Regeneration; Wound Healing; Neovascularization, Pathologic; Angiogenesis
PubMed: 38731540
DOI: 10.3390/molecules29092050 -
Scientific Reports Nov 2023Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been...
Retinal ischemia‒reperfusion (I/R) injury can cause significant damage to human retinal neurons, greatly compromising their functions. Existing interventions have been proven to have little effect. Ferroptosis is a newly discovered type of programmed cell death that has been found to be involved in the process of ischemia‒reperfusion in multiple organs throughout the body. Studies have shown that it is also present in retinal ischemia‒reperfusion injury. A rat model of retinal ischemia‒reperfusion injury was constructed and treated with deferoxamine. In this study, we found the accumulation of Fe, reactive oxygen species (ROS), malondialdehyde (MDA), and the consumption of glutathione (GSH) via ELISA testing; increased expression of transferrin; and decreased expression of ferritin, SLC7A11, and GPX4 via Western blotting (WB) and real-time PCR testing. Structural signs of ferroptosis (mitochondrial shrinkage) were observed across multiple cell types, including retinal ganglion cells (RGCs), photoreceptor cells, and pigment epithelial cells. Changes in visual function were detected by F-VEP and ERG. The results showed that iron and oxidative stress were increased in the retinal ischemia‒reperfusion injury model, resulting in ferroptosis and tissue damage. Deferoxamine protects the structural and functional soundness of the retina by inhibiting ferroptosis through the simultaneous inhibition of hemochromatosis, the initiation of transferrin, and the degradation of ferritin and activating the antioxidant capacity of the System Xc-GSH-GPX4 pathway.
Topics: Humans; Animals; Rats; Ferroptosis; Deferoxamine; Reperfusion; Vision, Low; Reperfusion Injury; Ferritins; Glutathione; Transferrins; Reactive Oxygen Species
PubMed: 37978208
DOI: 10.1038/s41598-023-46104-0 -
Drug Safety 1991Iron is an essential element for body homoeostasis, but there is no effective mechanism for elimination of an excess of this mineral. Deferoxamine (desferrioxamine) is... (Review)
Review
Iron is an essential element for body homoeostasis, but there is no effective mechanism for elimination of an excess of this mineral. Deferoxamine (desferrioxamine) is currently the treatment of choice for iron overload states from both acute iron intoxication and transfusion-dependent anaemias. The pharmacokinetics of deferoxamine are confounded both by its ability to chelate endogenous and exogenous iron and by the laboratory techniques used for its determination. Its iron-complex (ferrioxamine) has different pharmacokinetic properties. Because of its effectiveness, the use of deferoxamine is becoming more common, involving long term and high dose regimens. As a result of this, more and more toxicities that were not known in the past have been described and characterised. The most serious of these include hypotension, renal insufficiency, neurotoxicity, growth retardation and opportunistic infections: some of these side effects may be attributed to or aggravated by ferrioxamine. The pharmacological and toxicological literature on deferoxamine, and possible mechanisms for its toxicity, are reviewed and discussed.
Topics: Animals; Deferoxamine; Humans
PubMed: 2029352
DOI: 10.2165/00002018-199106010-00004 -
Journal of Biomaterials Applications Nov 2022Recently, Deferoxamine (DFO) and magnesium (Mg) have been identified as critical factors for angiogenesis and bone formation. However, in current research studies, there...
Recently, Deferoxamine (DFO) and magnesium (Mg) have been identified as critical factors for angiogenesis and bone formation. However, in current research studies, there is a lack of focus on whether DFO plus Mg can affect the regeneration of β-tricalcium phosphate (β-TCP) in osteoporosis and through what biological mechanisms. Therefore, the present work was aimed to preparation and evaluate the effect of Deferoxamine/magnesium modified β-tricalcium phosphate promotes (DFO/Mg-TCP) in ovariectomized rats model and preliminary exploration of possible mechanisms. The MC3T3-E1 cells were co-cultured with the exudate of DFO/Mg-TCP and induced to osteogenesis, and the cell viability, osteogenic activity were observed by Cell Counting Kit-8(CCK-8), Alkaline Phosphatase (ALP) staining, Alizarin Red Staining (RES) and Western Blot. In vitro experiments, CCK-8, ALP and ARS staining results show that the mineralization and osteogenic activity of MC3T3-E1increased significantly after intervention by DFO/Mg-TCP, as well as a higher levels of protein expressions including VEGF, OC, Runx-2 and HIF-1α. In vivo experiment, Micro-CT and Histological analysis evaluation show that DFO/Mg-TCP treatment presented the stronger effect on bone regeneration, bone mineralization and biomaterial degradation, when compared with OVX+Mg-TCP group and OVX+TCP group, as well as a higher VEGF, OC, Runx-2 and HIF-1α gene expression. The present study indicates that treatment with DFO/Mg-TCP was associated with increased regeneration by enhancing the function of osteoblasts in an OVX rat.
Topics: Rats; Animals; Magnesium; Deferoxamine; Vascular Endothelial Growth Factor A; Rats, Sprague-Dawley; Calcium Phosphates; Bone Regeneration; Osteogenesis; Cell Differentiation
PubMed: 35984333
DOI: 10.1177/08853282221121882 -
Current Drug Targets 2023Several studies demonstrated that deferoxamine, an iron chelator, can improve inflammatory alterations in adipose tissue induced by obesity. Obesity alterations in...
INTRODUCTION
Several studies demonstrated that deferoxamine, an iron chelator, can improve inflammatory alterations in adipose tissue induced by obesity. Obesity alterations in adipose tissue are also associated with tissue remodeling, and deferoxamine has anti-fibrosis action previously described in sites like the skin and liver.
METHODS
In this work, we analyzed deferoxamine effects on adipose tissue fibro-inflammation during obesity induced by diet in mice. approaches with fibroblasts and macrophages were also carried out to elucidate deferoxamine activity.
RESULTS
Our results demonstrated that in addition to exerting anti-inflammatory effects, reducing the cytokine production in adipose tissue of obese mice and by human monocyte differentiated in macrophage in vitro, deferoxamine can alter metalloproteinases expression and extracellular matrix production and .
CONCLUSION
Deferoxamine could be an alternative to control fibro-inflammation in obese adipose tissue, contributing to the metabolic improvements previously described.
Topics: Humans; Animals; Mice; Deferoxamine; Adipose Tissue; Obesity; Inflammation; Liver; Mice, Inbred C57BL; Insulin Resistance
PubMed: 37278033
DOI: 10.2174/1389450124666230602110705