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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 -
International Journal of Molecular... Jul 2021Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether...
Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in a replanted rat tooth model. Cell viability and inflammation were evaluated in RAW264.7 cells. Osteoclastogenesis was confirmed by tartrate-resistant acid phosphatase staining, reactive oxygen species (ROS) measurement, and quantitative reverse transcriptase-polymerase chain reaction in teeth exposed to different concentrations of DFO. In vivo, molars of 31 six-week-old male Sprague-Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. DFO downregulated the genes related to inflammation and osteoclastogenesis. DFO also reduced ROS production and regulated specific pathways. Furthermore, the results of the micro-CT and histological analyses provided evidence of the decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus, it has to be further investigated as a root surface treatment option for an avulsed tooth.
Topics: Alveolar Bone Loss; Animals; Anti-Inflammatory Agents; Bone Regeneration; Deferoxamine; Male; Mice; Osteoclasts; Osteogenesis; RAW 264.7 Cells; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tooth Avulsion
PubMed: 34360988
DOI: 10.3390/ijms22158225 -
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 -
Toxicology and Industrial Health Nov 2022An 86-year-old man presented to the emergency room with vomiting and melena. The patient was hemodynamically stable and remained alert and orientated. According to his...
An 86-year-old man presented to the emergency room with vomiting and melena. The patient was hemodynamically stable and remained alert and orientated. According to his family, ingestion of a pack of disposable hand warmers, which he mistook for black sesame powder, occurred 17 h prior to admission. Before ingestion, he mixed the powder with warm water. Physical examination revealed no thermal injury of the oral mucosa with no abdominal pain or tenderness. An abdominal plain film showed multiple scattered radiopaque material with zonal distribution over the right abdomen. An intravenous 500-mg deferoxamine challenge test showed no vin rosé urine discoloration. Serial serum iron levels remained within the normal range. The patient remained clinically stable with no medical complications. He was discharged 3 days after admission. The hand warmers consisted of iron powder (50% w/w), sodium chloride, activated charcoal, and nontoxic vermiculite: a potential risk for intestinal thermal injury. In this case, the water added beforehand rapidly terminated the iron oxidation reaction. This explained the lack of thermal injury. Ferric oxide is poorly absorbed by the digestive tract and explained the absence of iron intoxication. Therefore, clinicians should clarify the method of ingestion. If a hand warmer has been premixed with water, less mucosa injury can be expected with a lower risk of iron intoxication. This report also provided evidence that abdominal plain films can be used to confirm the ingestion of iron and monitor its elimination.
Topics: Male; Humans; Aged, 80 and over; Charcoal; Deferoxamine; Water; Sodium Chloride; Powders; Iron
PubMed: 36062486
DOI: 10.1177/07482337221124666 -
EMBO Molecular Medicine Feb 2023Ocular and specifically retinal toxicities of systemic medications are prevalent and encompass many disease modalities. For many of these pharmaceuticals, established...
Ocular and specifically retinal toxicities of systemic medications are prevalent and encompass many disease modalities. For many of these pharmaceuticals, established follow-up protocols are in place to ensure timely detection and cessation of therapy. However, while for some disorders, cessation of therapy is a viable option due to existing treatment alternatives, for some others cessation of treatment can be life threatening and/or shorten the patient's life expectancy. Such is the case for iron chelating agents used in transfusion-dependent patients of Thalassemia, of which deferoxamine (DFO) is the most widely used. In their recent article in EMBO Molecular Medicine, Kong et al (2023) addressed the issue of DFO-induced retinal toxicity used both in vivo and in vitro techniques. Their study suggests a potentially protective role for α-ketoglutarate (AKG) supplementation against DFO toxicity.
Topics: Humans; Deferoxamine; Lifting; Iron Chelating Agents; Thalassemia
PubMed: 36715217
DOI: 10.15252/emmm.202217259 -
Nanomedicine (London, England) Sep 2022To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. The pharmacokinetics of DFO-NPs...
To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. The pharmacokinetics of DFO-NPs were evaluated in Sprague-Dawley rats at three doses (3.3, 10 and 30 μmol/kg) after intravenous and subcutaneous administration. DFO-NPs exhibited a biphasic concentration-time profile after intravenous administration with a short terminal half-life (2.0-3.2 h), dose-dependent clearance (0.111-0.179 l/h/kg), minimal tissue distribution and exclusive renal excretion with a possible saturable reabsorption mechanism. DFO-NPs after subcutaneous administration exhibited absorption-rate-limited kinetics with a prolonged half-life (5.7-10.1 h) and favorable bioavailability (47-107%). DFO-NPs exhibit nonlinear pharmacokinetics with increasing dose, and subcutaneous administration substantially improves drug exposure, thereby making it a clinically viable administration route for iron chelation.
Topics: Rats; Animals; Deferoxamine; Iron Chelating Agents; Tissue Distribution; Rats, Sprague-Dawley; Iron Overload
PubMed: 36547231
DOI: 10.2217/nnm-2022-0159 -
Expert Opinion on Therapeutic Targets Dec 2017Intraventricular hemorrhage (IVH) affects both premature infants and adults. In both demographics, it has high mortality and morbidity. There is no FDA approved therapy... (Review)
Review
Intraventricular hemorrhage (IVH) affects both premature infants and adults. In both demographics, it has high mortality and morbidity. There is no FDA approved therapy that improves neurological outcome in either population highlighting the need for additional focus on therapeutic targets and treatments emerging from preclinical studies. Areas covered: IVH induces both initial injury linked to the physical effects of the blood (mass effect) and secondary injury linked to the brain response to the hemorrhage. Preclinical studies have identified multiple secondary injury mechanisms following IVH, and particularly the role of blood components (e.g. hemoglobin, iron, thrombin). This review, with an emphasis on pre-clinical IVH research, highlights therapeutic targets and treatments that may be of use in prevention, acute care, or repair of damage. Expert opinion: An IVH is a potentially devastating event. Progress has been made in elucidating injury mechanisms, but this has still to translate to the clinic. Some pathways involved in injury also have beneficial effects (coagulation cascade/inflammation). A greater understanding of the downstream pathways involved in those pathways may allow therapeutic development. Iron chelation (deferoxamine) is in clinical trial for intracerebral hemorrhage and preclinical data suggest it may be a potential treatment for IVH.
Topics: Adult; Animals; Cerebral Hemorrhage; Deferoxamine; Humans; Infant; Infant, Premature; Iron Chelating Agents; Molecular Targeted Therapy
PubMed: 29067856
DOI: 10.1080/14728222.2017.1397628 -
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 -
Hematology/oncology Clinics of North... Apr 2023Conventional therapy for severe thalassemia includes regular red cell transfusions and iron chelation therapy to prevent and treat complications of iron overload. Iron... (Review)
Review
Conventional therapy for severe thalassemia includes regular red cell transfusions and iron chelation therapy to prevent and treat complications of iron overload. Iron chelation is very effective when appropriately used, but inadequate iron chelation therapy continues to contribute to preventable morbidity and mortality in transfusion-dependent thalassemia. Factors that contribute to suboptimal iron chelation include poor adherence, variable pharmacokinetics, chelator adverse effects, and difficulties with precise monitoring of response. The regular assessment of adherence, adverse effects, and iron burden with appropriate treatment adjustments is necessary to optimize patient outcomes.
Topics: Humans; beta-Thalassemia; Iron Chelating Agents; Deferiprone; Deferoxamine; Pyridones; Iron Overload; Thalassemia; Iron
PubMed: 36907610
DOI: 10.1016/j.hoc.2022.12.013 -
Biomolecules Aug 2023Diabetic nephropathy (DN) is one of the most devastating diabetic microvascular complications. It has previously been observed that iron metabolism levels are abnormal...
Diabetic nephropathy (DN) is one of the most devastating diabetic microvascular complications. It has previously been observed that iron metabolism levels are abnormal in diabetic patients. However, the mechanism by which iron metabolism levels affect DN is poorly understood. This study was designed to evaluate the role of iron-chelator deferoxamine (DFO) in the improvement of DN. Here, we established a DN rat model induced by diets high in carbohydrates and fat and streptozotocin (STZ) injection. Our data demonstrated that DFO treatment for three weeks greatly attenuated renal dysfunction as evidenced by decreased levels of urinary albumin, blood urea nitrogen, and serum creatinine, which were elevated in DN rats. Histopathological observations showed that DFO treatment improved the renal structures of DN rats and preserved podocyte integrity by preventing the decrease of transcripts of nephrin and podocin. In addition, DFO treatment reduced the overexpression of fibronectin 1, collagen I, IL-1β, NF-κB, and MCP-1 in DN rats, as well as inflammatory cell infiltrates and collagenous fibrosis. Taken together, our findings unveiled that iron chelation via DFO injection had a protective impact on DN by alleviating inflammation and fibrosis, and that it could be a potential therapeutic strategy for DN.
Topics: Animals; Rats; Diabetic Nephropathies; Deferoxamine; Inflammation; Fibrosis; Iron Chelating Agents; Iron; Diabetes Mellitus
PubMed: 37627331
DOI: 10.3390/biom13081266