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PloS One 2015Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition.... (Review)
Review
Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.
Topics: Animals; Cerebral Hemorrhage; Deferoxamine; Disease Models, Animal; Mice; Rats; Siderophores; Swine; Treatment Outcome
PubMed: 26000830
DOI: 10.1371/journal.pone.0127256 -
Annals of Medicine and Surgery (2012) May 2023COVID-19 infection is associated with high mortality, and despite extensive studying the scientific society is still working to find a definitive treatment. Some experts...
UNLABELLED
COVID-19 infection is associated with high mortality, and despite extensive studying the scientific society is still working to find a definitive treatment. Some experts postulated a beneficial role of Deferoxamine.
AIM
The aim of this study was to compare the outcomes of COVID-19 adult patients admitted to the ICU who received deferoxamine to those who received standard of care.
METHODS
Prospective observational cohort study, in the ICU of a tertiary referral hospital in Saudi Arabia to compare all-cause hospital mortality between COVID-19 patients who received deferoxamine and standard of care.
RESULTS
A total of 205 patients were enrolled, with an average age of 50.1±14.3, 150 patients received standard of care only, and 55 patients received deferoxamine additionally. Hospital mortality was lower in deferoxamine group (25.5 vs. 40.7%, 95% CI=1.3-29.2%; =0.045). Clinical status score upon discharge was lower in deferoxamine group (3.6±4.3 vs. 6.2±4, 95% CI: 1.4-3.9; <0.001), as was the difference between discharge score and admission score (indicating clinical improvement). More patients admitted with mechanical ventilation were successfully extubated in the deferoxamine group (61.5 vs. 14.3%, 95% CI: 15-73%; =0.001), with a higher median ventilator-free days. There were no differences between groups in adverse events. Deferoxamine group was associated with hospital mortality [odds ratio=0.46 (95% CI: 0.22-0.95); =0.04].
CONCLUSIONS
Deferoxamine may have mortality and clinical improvement benefits in COVID-19 adults admitted to ICU. Further powered and controlled studies are required.
PubMed: 37229096
DOI: 10.1097/MS9.0000000000000392 -
International Journal of Nanomedicine 2022Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone...
INTRODUCTION
Bone delay union is mostly caused by lack of blood supply. Although autografts, allografts and artificial bone have been widely used to treat bone delay union, the bone regeneration fails in the ischemic site accompanied by the bone donor site complications and disease transmission. Recently, there is a growing recognition of the importance of hydrogel scaffolds which are regarded as an eligible engineer tissue for bone repair. However, hydrogel is still limited in improving neovascularization.
METHODS
In this work, black phosphorus nanosheet and deferoxamine (BPN-DFO) were loaded in the gelatin hydrogel to overcome the high risk of bone delay union and systemically investigated the regeneration capability of BPN-DFO hydrogel in vitro and vivo.
RESULTS
The resulting BPN-DFO hydrogel scaffold showed superior swollen, degradation and release rate, as well as satisfied biocompatibility. BPN-DFO hydrogel shown the significant up-expression of mRNA related to bone regeneration and cell proliferation. In vivo, the proposed BPN-DFO hydrogel significantly improved osteogenesis and neovascularization in the ischemic tibial bone site of SD rats with acute femoral artery occlusion. Both macroscopic and histological evaluation of new regenerated bone showed newly formed blood vessel and collagen using BPN-DFO hydrogel. The immunohistochemistry and RT-PCR revealed that the bone regeneration could be improved via BMP/Runx2 pathway.
CONCLUSION
The BPN-DFO hydrogel possesses potential tissue engineer material for ischemic bone defect treatment. However, furthermore studies are needed to testify the safety and efficacy of BPN-DFO hydrogel.
Topics: Animals; Bone Regeneration; Deferoxamine; Fracture Healing; Gelatin; Hydrogels; Ischemia; Nanostructures; Phosphorus; Rats; Rats, Sprague-Dawley; Tibia; Tissue Engineering; Tissue Scaffolds
PubMed: 35299865
DOI: 10.2147/IJN.S351814 -
American Journal of Physiology. Heart... Feb 2023Diabetes increases the risk of poststroke cognitive impairment (PSCI). Greater hemorrhagic transformation (HT) after stroke is associated with vasoregression and...
Diabetes increases the risk of poststroke cognitive impairment (PSCI). Greater hemorrhagic transformation (HT) after stroke is associated with vasoregression and cognitive decline in male diabetic rats. Iron chelator deferoxamine (DFX) prevents vasoregression and improves outcomes. Although diabetic female rats develop greater HT, its impact on poststroke cerebrovascularization and cognitive outcomes remained unknown. We hypothesized that diabetes mediates pathological neovascularization, and DFX attenuates poststroke cerebrovascular remodeling and improves neurological outcomes in female diabetic rats. Female control and diabetic animals were treated with DFX or vehicle for 7 days after stroke. Vascular indices, microglial activation, and blood-brain barrier (BBB) integrity were evaluated on . Results from diabetic female rats were partially compared with our previously published findings in male counterparts. Hemin-induced programmed cell death was studied in male and female brain microvascular endothelial cell lines (BMVEC). There was no vasoregression after stroke in either control or diabetic female animals. DFX prevented diabetes-mediated gliovascular remodeling and compromised BBB integrity while improving memory function in diabetes. Comparisons of female and male rats indicated sex differences in cognitive and vascular outcomes. Hemin mediated ferroptosis in both male and female BMVECs. DFX improved survival but had differential effects on ferroptosis signaling in female and male cells. These results suggest that stroke and associated HT do not affect cerebrovascularization in diabetic female rats, but iron chelation may provide a novel therapeutic strategy in the prevention of poststroke memory impairment in females with diabetes via the preservation of gliovascular integrity and improvement of endothelial cell survival. The current study shows for the first time that diabetes does not promote aberrant cerebrovascularization in female rats. This contrasts with what we reported in male animals in various diabetes models. Deferoxamine preserved recognition memory function in diabetic female animals after stroke. The effect(s) of stroke and deferoxamine on cerebrovascular density and microglial activation also appear(s) to be different in female diabetic rats. Lastly, deferoxamine exerts detrimental effects on animals and BMVECs under control conditions.
Topics: Rats; Female; Male; Animals; Deferoxamine; Diabetes Mellitus, Experimental; Ferroptosis; Hemin; Stroke
PubMed: 36563009
DOI: 10.1152/ajpheart.00490.2022 -
Aging Sep 2021Senescence reduces the circulating number and angiogenic activity of endothelial progenitor cells (EPCs), and is associated with aging-related vascular diseases....
Senescence reduces the circulating number and angiogenic activity of endothelial progenitor cells (EPCs), and is associated with aging-related vascular diseases. However, it is very time-consuming to obtain aged cells (~1 month of repeated replication) or animals (~2 years) for senescence studies. Here, we established an accelerated senescence model by treating EPCs with deferoxamine (DFO), an FDA-approved iron chelator. Four days of low-dose (3 μM) DFO induced senescent phenotypes in EPCs, including a senescent pattern of protein expression, impaired mitochondrial bioenergetics, altered mitochondrial protein levels and compromised angiogenic activity. DFO-treated early EPCs from young and old donors (< 35 vs. > 70 years old) displayed similar senescent phenotypes, including elevated senescence-associated β-galactosidase activity and reduced relative telomere lengths, colony-forming units and adenosine triphosphate levels. To validate this accelerated senescence model , we intraperitoneally injected Sprague-Dawley rats with DFO for 4 weeks. Early EPCs from DFO-treated rats displayed profoundly senescent phenotypes compared to those from control rats. Additionally, in hind-limb ischemic mice, DFO pretreatment compromised EPC angiogenesis by reducing both blood perfusion and capillary density. DFO thus accelerates EPC senescence and appears to hasten model development for cellular senescence studies.
Topics: Aging; Animals; Cell Proliferation; Cells, Cultured; Cellular Senescence; Deferoxamine; Endothelial Progenitor Cells; Hindlimb; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitochondria; Neovascularization, Pathologic; Rats; Rats, Sprague-Dawley; Telomerase
PubMed: 34508614
DOI: 10.18632/aging.203469 -
Plastic and Reconstructive Surgery Jun 2019Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound...
BACKGROUND
Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic.
METHODS
The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05).
RESULTS
For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis.
CONCLUSION
Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Therapeutic, V.
Topics: Analysis of Variance; Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Deferoxamine; Dose-Response Relationship, Radiation; Female; Humans; Imaging, Three-Dimensional; Iron; Radiation Dosage; Sensitivity and Specificity; Triple Negative Breast Neoplasms
PubMed: 30907808
DOI: 10.1097/PRS.0000000000005647 -
Journal of Oral Biology and... 2022Resveratrol and oxyresveratrol, a resveratrol derivative, possess various pharmacological activities, including anti-cancer activities. Because cancer stem cells play an...
OBJECTIVES
Resveratrol and oxyresveratrol, a resveratrol derivative, possess various pharmacological activities, including anti-cancer activities. Because cancer stem cells play an important role in cancer recurrence, the aims of this study were to investigate whether resveratrol or oxyresveratrol can inhibit the expression of cancer stem cell markers under hypoxia.
MATERIALS AND METHODS
Deferoxamine was used to mimic the hypoxic condition. The mRNA expression of cancer stem cell markers was analyzed by Real-time PCR. Flow cytometry was used to determine the number of and cells.
RESULTS
Deferoxamine dose-dependently induced the expression of cancer stem cell markers; , , , and . The induction of these cancer stem cells markers was inhibited when the cells were treated with either resveratrol or oxyresveratrol. Moreover, we found that resveratrol also reduced the number of and cells after deferoxamine treatment.
CONCLUSIONS
Resveratrol and oxyresveratrol inhibit the expression of cancer stem cell markers and might target cancer stem cells in a hypoxia-associated tumor.
PubMed: 35313655
DOI: 10.1016/j.jobcr.2022.03.003 -
Stroke Jul 2022There are limited data on the trajectory of recovery and long-term functional outcomes after intracerebral hemorrhage (ICH). Most ICH trials have conventionally assessed... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
There are limited data on the trajectory of recovery and long-term functional outcomes after intracerebral hemorrhage (ICH). Most ICH trials have conventionally assessed outcomes at 3 months following the footsteps of ischemic stroke. The i-DEF trial (Intracerebral Hemorrhage Deferoxamine Trial) assessed modified Rankin Scale (mRS) longitudinally at prespecified time points from day 7 through the end of the 6-month follow-up period. We evaluated the trajectory of mRS among trial participants and examined the effect of deferoxamine on this trajectory.
METHODS
We performed a post hoc analysis of the i-DEF trial, a multicenter, randomized, placebo-controlled, double-blind, futility-design, phase 2 clinical trial, based on the actual treatment received. Favorable outcome was defined as mRS score of 0-2. A generalized linear mixed model was used to evaluate the outcome trajectory over time, as well as whether the trajectory was altered by deferoxamine, after adjustments for randomization variables, presence of intraventricular hemorrhage, and ICH location.
RESULTS
A total of 291 subjects were included in analysis (145 placebo and 146 deferoxamine). The proportion of patients with mRS score of 0-2 continually increased from day 7 to 180 in both groups (interaction <0.0001 for time in main effects model), but treatment with deferoxamine favorably altered the trajectory (interaction =0.0010). Between day 90 and 180, the deferoxamine group improved (=0.0001), whereas there was not significant improvement in the placebo arm (=0.3005).
CONCLUSIONS
A large proportion of patients continue to improve up to 6 months after ICH. Future ICH trials should assess outcomes past 90 days for a minimum of 6 months. In i-DEF, treatment with deferoxamine seemed to accelerate and alter the trajectory of recovery as assessed by mRS.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT02175225.
Topics: Humans; Cerebral Hemorrhage; Deferoxamine; Double-Blind Method; Medical Futility; Treatment Outcome
PubMed: 35306827
DOI: 10.1161/STROKEAHA.121.037298 -
The British Journal of Dermatology Apr 2017
Review
Topics: Administration, Cutaneous; Chronic Disease; Deferoxamine; Humans; Iron; Siderophores; Skin Ulcer; Wound Healing; Wounds and Injuries
PubMed: 28418133
DOI: 10.1111/bjd.14956 -
Biomaterials Science May 2020Bone regeneration is a complex process in which angiogenesis and osteogenesis are crucial. Introducing multiple angiogenic and osteogenic cues simultaneously into a...
Bone regeneration is a complex process in which angiogenesis and osteogenesis are crucial. Introducing multiple angiogenic and osteogenic cues simultaneously into a single system and tuning these cues to optimize the niche remains a challenge for bone tissue engineering. Herein, based on our injectable biomimetic hydrogels composed of silk nanofibers (SNF) and hydroxyapatite nanoparticles (HA), deferoxamine (DFO) and bone morphogenetic protein-2 (BMP-2) were loaded on SNF and HA to introduce more angiogenic and osteogenic cues. The angiogenesis and osteogenesis capacity of injectable hydrogels could be regulated by tuning the delivery of DFO and BMP-2 independently, resulting in vascularization and bone regeneration in cranial defects. The angiogenesis and osteogenesis outcomes accelerated the regeneration of vascularized bones toward similar composition and structure to natural bones. Therefore, the multiple biophysical and chemical cues provided by the nanofibrous structures, organic-inorganic compositions, and chemical and biochemical angiogenic and osteogenic inducing cues suggest the potential for clinical applicability of these hydrogels in bone tissue engineering.
Topics: Animals; Bone Morphogenetic Protein 2; Bone Regeneration; Deferoxamine; Durapatite; Hydrogels; Injections; Male; Mesenchymal Stem Cells; Nanofibers; Nanoparticles; Osteogenesis; Rats, Sprague-Dawley; Silk; Tissue Engineering
PubMed: 32215404
DOI: 10.1039/d0bm00104j