Deferoxamine mesylate improves the repair of jaw bone defects in an ovariectomized rat model of osteoporosis / 中国组织工程研究

BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P＜0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P＜0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P＜0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P＜0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.

Application of deferoxamine in bone tissue regeneration / 中国组织工程研究

BACKGROUND:Aside from iron chelating,deferoxamine is also considered as an effective hypoxia mimetic agent and hypoxia inducible factor-1α stabilizer.Deferoxamine has played a favorable effect on bone regeneration in both basic and clinical research recently.Deferoxamine solutions or deferoxamine loaded bio-scaffolds have been locally applied in bone tissue engineering,and their promotion of bone repair involves various functional properties and molecular mechanisms which have not been entirely clarified.Moreover,their advances in research of bone regeneration lack comprehensive summary as well. OBJECTIVE:To review the functional properties,relative merits and advances in basic research and clinical practice of deferoxamine applied in bone regeneration,attempting to provide references and strategies for further studies. METHODS:Relevant articles were searched with the key words of"deferoxamine OR desferrioxamine OR desferal OR DFO,""bone tissue engineering OR bone regeneration OR bone remodeling OR bone repair OR bone healing OR osteogenesis,""angiogenesis OR vascularized bone regeneration OR angiogenic-osteogenic coupling"in English and Chinese by using PubMed,WanFang and CNKI databases.Eventually,88 articles were selected for review. RESULTS AND CONCLUSION:Deferoxamine can recruit stem cells and regulate their function,activate relevant signaling pathways to advance hypoxia adaptation of the cells,exert anti-inflammatory and antioxidant properties to improve local inflammatory environment,and promote bone regeneration by coupling osteogenesis and angiogenesis as well as inhibiting bone resorption.Compared with growth factors or peptides loaded in conventional bone tissue engineering,deferoxamine has its unique advantages as a small molecule drug,while it also has toxic reactions and application limitations.Therefore,it is necessary to optimize its loading form and dosagey.The unique angiogenic-osteogenic coupling ability of deferoxamine can be used in different types of bone injuries including fractures,osteonecrosis,distraction osteogenesis,bone grafting,oral related osteogenesis,and bone defects.Due to the enhancement of angiogenesis,this ability enables deferoxamine to better adapt and solve the difficulties in bone repair caused by the complex and variable clinical situations and individual differences.However,it is also necessary to compare and optimize the application methods and safe dosage of deferoxamine to expand its application scope and enhance its clinical value.

An injectable bioactive dressing based on platelet-rich plasma and nanoclay: Sustained release of deferoxamine to accelerate chronic wound healing

Delayed diabetic wound healing has placed an enormous burden on society. The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis. Platelet-rich plasma (PRP) gel, a popular biomaterial in the field of regeneration, has limited applications due to its non-injectable properties and rapid release and degradation of growth factors. Here, we prepared an injectable hydrogel (DPLG) based on PRP and laponite by a simple one-step mixing method. Taking advantages of the non-covalent interactions, DPLG could overcome the limitations of PRP gels, which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine (an angiogenesis promoter). DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in type I diabetic rats and normal rats. Taken together, this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.

Naringin is a promising natural compound for therapy of iron-overload disorders

Abstract Naringin has been shown to exhibit satisfying iron chelation capacity. Considering the side effects of routinely-used iron chelator (desferrioxamine, DFO), we decided to evaluate the iron chelation potency of naringin to discover whether or not it can be a promising natural substitute for treatment of excessive iron-related diseases. 35 mice were classified into five groups of 7 and subjected to iron dextran administration to induce the iron-overload condition. Iron-overloaded mice were then treated with normal saline (as control), naringin or DFO Morphology changes, and iron deposition in liver tissues were studied using H&E and Perl's staining. The results revealed that naringin is more potent than DFO in removing excessive iron ions deposited in liver tissues, indicating that naringin is a promising natural compound for therapy of iron overload disorders

Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1

Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in

Early constant observation of the effect of deferoxamine mesylate on improvement of vascularized bone regeneration in SD rat skull critical size defect model / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of local administration of deferoxamine mesylate (DFO) on vascularization and osteogenesis and its ability to maintain the activity of hypoxia inducible factor-1α (HIF-1α), by constantly observing early changes of vessel-like structures and bone tissues during bone defects healing.@*METHODS@#Skull critical bone defect models were constructed on a total of thirty male SD rats (6-8 weeks old). The rats were randomly divided into experimental group (DFO group) or control group (normal saline group). 300 μL 200 μmol/L DFO solution or normal saline was locally injected on the 4th day after the defect was made. On the 5th, 7th, 10th, 14th, and 28th days after surgery, three rats in each group were sacrificed respectively. HE staining and Masson staining were performed to observe new bone formation and mineralization. HIF-1α immunohistochemistry staining was performed to examine relative expression of protein. Qualitative analysis and comparation were performed by t-tests on relative expression of HIF-1α, numbers of blood vessels and percentages of mineralization tissues of new bone areas.@*RESULTS@#On the 5th, 7th, 10th, 14th and 28th days after surgery, the average numbers of blood vessels were 30.40±12.15, 62.00±17.87, 73.43±15.63, 40.00±7.84, 48.71±11.64 in the DFO group, and 18.75±6.63, 19.13±2.80, 51.35±16.21, 27.18±7.32, 30.88±13.43 in the control group. The number of blood vessels in the DFO group was significantly higher than that of the control group at each time point (P < 0.05). The mass of new bone in the DFO group was higher than that in the control group on the 14th and 28th days after surgery. The percentage of mineralization tissues of new bone area on the 14th and 28th days after injection were (27.73±5.93)% and (46.53±3.66)% in the DFO group, and (11.99±2.02)% and (31.98±4.22)% in the control group. The percentage of mineralization tissues in the DFO group was significantly higher than that of the control group at each time point (P < 0.001). The relative expression of HIF-1α in the DFO group compared with the control group was 2.86±0.48, 1.32±0.26, 1.32±0.32, 1.28±0.38 and 1.05±0.34 on the 5th, 7th, 10th, 14th and 28th days, with significant expression difference on the 5th day (P < 0.01).@*CONCLUSION@#Use of DFO in bone defects promotes vascularization and osteogenesis in the defect area, and maintains the protein activity of HIF-1α temporarily.

Bilateral maculopathy in a thalassemia patient on iron chelation therapy: a case report / Maculopatia bilateral em paciente com talassemia em terapia quelante de ferro: relato de caso

ABSTRACT A 10-year-old Malay girl with underlying HbE/beta-thalassemia, on regular blood transfusion and deferoxamine iron chelation therapy, presented with two-month history of bilateral blurring of vision. On examination, her vision was 6/36 both eyes. Other optic nerve functions were normal. Anterior segment examination of both eyes was unremarkable. Fundus examination of both eyes revealed dull foveal reflex. Optical coherence tomography of both maculae showed increased central subfield thickness. Fundus fluorescence angiography showed patchy hypofluorescence over macular region for both eyes and late staining, indicating retinal pigment epithelium anomalies. A diagnosis of iron-chelation-therapy-related bilateral maculopathy was made. Patient was co-managed with pediatric hematology team to adjust the dose of deferoxamine, and was given three monthly appointments to monitor the progression of maculopathy at the ophthalmology clinic. However patient defaulted ophthalmology follow-up after the first visit.

RESUMO Uma menina malaia de 10 anos de idade com doença de base- B/beta-talassemia, em transfusão de sangue regular e terapia quelante de ferro deferoxamina, apresentou história de dois meses de visão turva bilateral. Ao exame, sua visão era de 6/36 em ambos os olhos. Outras funções do nervo óptico estavam normais. O exame do segmento anterior de ambos os olhos foi normal. Exame do fundo de ambos os olhos revelou reflexo foveal opaco. A tomografia de coerência óptica de ambas as máculas mostrou aumento da espessura do subcampo central. A angiografia de fluorescência do fundo mostrou hipofluorescência irregular sobre a região macular de ambos os olhos e coloração tardia, indicando anomalias de epitélio pigmentar da retina. Um diagnóstico de maculopatia bilateral relacionada à terapia quelante de ferro foi feito. A paciente foi avaliada em conjunto com a equipe de hematologia pediátrica para ajustar a dose de deferoxamina, e foram oferecidas três consultas mensais na clínica oftalmológica, para monitorar a progressão da maculopatia. No entanto, ela não compareceu para acompanhamento oftalmológico após a primeira visita.

Mechanism of participation of osteocytes in the formation of osteoclasts under hypoxia / 华西口腔医学杂志

OBJECTIVE@#To investigate the mechanism of the participation of osteocytes in the formation of osteoclasts under hypoxia.@*METHODS@#The hypoxia culture system of osteocyte-like cell line MLO-Y4 was established by deferoxamine mesylate (DFO) in vitro. The proliferation of MLO-Y4 cells was examined by CCK-8 cell proliferation/toxicity assay. RAW264.7 cells were induced to osteoclasts by the conditioned medium containing the cultured MLO-Y4. Tartrate-resistant acid phosphatase (TRAP) staining was performed on day 7. Quantitative real-time fluorescence polymerase chain reaction, immunofluorescence, and Western blot were used to detect the expression levels of hypoxia-inducible factor (HIF)-1α and receptor activator of nuclear factor-κB ligand (RANKL) in MLO-Y4 under hypoxia. The effects of siHIF-1α on the expression levels of HIF-1α and RANKL in MLO-Y4 under the same conditions were detected.@*RESULTS@#DFO (100 μmol·L⁻¹) promoted the proliferation of MLO-Y4 at 24 h, which decreased with time (P<0.01). After the addition of soluble sRANKL, the formation of osteoclasts was significantly increased in the DFO group (P<0.001). The expression of RANKL mRNA in MLO-Y4 under 100 μmol·L⁻¹ DFO increased first and then decreased with the duration of hypoxia. This expression reached a peak at 24 h (P<0.01). Hypoxia up-regulated the expression of HIF-1α and RANKL protein (P<0.01). Under hypoxia, siHIF-1α downregulated the expression of HIF-1α and RANKL (P<0.01). siHIF-1α also decreased the number of osteoclasts (P<0.01).@*CONCLUSIONS@#Under hypoxia, MLO-Y4 could facilitate the formation of RANKL through upre-gulating the expression of HIF-1α protein, thereby accelerate the differentiation of RAW264.7 cells into osteoclasts.

Experimental study on the prevention of bone loss by deferoxamine in type 1 diabetic mice with osteoporosis / 中华内分泌代谢杂志

Objective To observe the effect of a hypoxia mimicking agent deferoxamine (DFO) on the mineral density,volume,architecture,strength,and metabolism of the bones in type 1 diabetic mice withosteoporosis.Methods Type 1 diabetic mice model was established by intraperitoneal injections of streptozotocin.The mice were divided into control (normal mice),diabetes mellitus,and DFO groups.Micro-CT was used to analyze the bone mineral density,volume,architecture,and strength of the trabecule in the distal part of femurs.Three point bending test was carried out to evaluate the bone strength.Hematoxylin and eosin (HE) staining was performed to observe the alteration in the number of osteoblasts.Real-time PCR was used to detect the mRNA expressions of Runt-related gene 2 (Runx-2),osteoclacin,and tartrate resistant acid phosphatase (TRAP) in tibias.Western blot was used to detect the protein expressions of Hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor (VEGF) in tibias.Results There was a decrease in mineral density,volume,strength of bones as well as deteriorated trabecular microarchitecture in diabetic mice as compared to control mice,which were partially improved by DFO treatment.Moreover,DFO treatment increased the number of osteoblasts and mRNA expression levels of Runx-2,osteoclacin,TRAP,as well as protein expression levels of HIF-1 α and VEGF(P＜0.05).Conclusion Bone loss could be partially prevented by DFO treatment in type 1 diabetic osteoporosis mice,which might be ascribed to increased bone formation via stimulating hypoxia inducible factor singnaling pathway.

Effect of deferoxamine on hyperoxic lung injury in rats / 中华麻醉学杂志

Objective@#To evaluate the effect of deferoxamine on hyperoxic lung injury in rats.@*Methods@#Twenty-four adult male Sprague-Dawley rats, weighing 170-230 g, were divided into 3 groups (n=8 each) using a random number table method: hyperoxia group (group H), deferoxamine group (group D) and air control group (group C). Mechanical ventilation was performed after tracheal intubation, group C inhaled air, and H and D groups inhaled 90% oxygen.Deferoxamine 50 mg·kg-1·h-1 was continuously infused via the tail vein for 4 h via the tail vein at the same time of mechanical ventilation in group D. The equal volume of normal saline was infused in H and C groups.At 4 h of mechanical ventilation, lungs were removed for examination of pathological changes of lung tissues and for determination of wet/dry weight ratio (W/D ratio) and levels of pulmonary surfactant protein C (SP-C), xanthine oxidase (XOD) and glutathione reductase (GR) in lung tissues and broncho-alveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay.@*Results@#Compared with group C, the pathological score of lung tissues and W/D ratio were significantly increased, the levels of SP-C and GR in lung tissues and BALF were decreased, and the level of XOD in lung tissues and BALF was increased in H and D groups (P<0.05). Compared with group H, the pathological score of lung tissues and W/D ratio were significantly decreased, the levels of SP-C and GR in lung tissues and BALF were increased, and the level of XOD in lung tissues and BALF was decreased in group D (P<0.05).@*Conclusion@#Deferoxamine can inhibit oxidative stress response and alleviate hyperoxic lung injury in rats.

The role of DFO in Al (mal) 3-induced ferroptosis in PC12 cells / 中华劳动卫生职业病杂志

Objective@#To investigate the mechanism of Al (mal) 3-induced ferroptosis in rat adrenal pheochromocytoma cells (PC12), to explore the effect of deferoxamine (DFO) .@*Methods@#Taken PC12 cells growing at logarithmic phase and divided into 6 groups: control group, 200 μmol/L Al (mal) 3 group, 0.5% DMSO group, 200 μmol/L DFO group, Al (mal) 3+DMSO group, Al (mal) 3+DFO group. DMSO and DFO were added to the DMSO group and the Al (mal) 3+DMSO group, the DFO group and the Al (mal) 3+DFO group for 2 h, respectively, Al (mal) 3 was then added to the Al (mal) 3 group, Al (mal) 3+DMSO group, and the Al (mal) 3+DFO group to a final concentration of 200 μmol/L. The cell viability was detected by CCK8, the morphology and ROS levels of PC12 cells was observed by inverted microscope, the cell proliferation toxicity and intracellular iron ion content were detected by colorimetry, the GSH content and GSH-PX activity were detected by biochemical method.@*Results@#Al (mal) 3 exposure significantly inhibited the growth of PC12 cells and destroyed the cell morphological structure, resulting in increased LDH activity and intracellular iron ion content in PC12 cells, decreased GSH content and GSH-PX activity, increased ROS levels; the combined treatment of Al (mal) 3+DFO can significantly improve the cell viability of PC12 cells, improved cell morphology, decreased cell LDH activity and intracellular iron ion content (P>0.05), increased GSH content and GSH-PX activity, decreased ROS levels.@*Conclusion@#Al (mal) 3 can induce ferroptosis in PC12 cells, DFO may inhibit ferroptosis by reducing intracellular iron levels and reducing oxidative damage.

Effect of deferoxamine on hyperoxic lung injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of deferoxamine on hyperoxic lung injury in rats.Methods Twenty-four adult male Sprague-Dawley rats,weighing 170-230 g,were divided into 3 groups (n=8 each) using a random number table method:hyperoxia group (group H),deferoxamine group (group D) and air control group (group C).Mechanical ventilation was performed after tracheal intubation,group C inhaled air,and H and D groups inhaled 90％ oxygen.Deferoxamine 50 mg · kg-1 · h-1 was continuously infused via the tail vein for 4 h via the tail vein at the same time of mechanical ventilation in group D.The equal volume of normal saline was infused in H and C groups.At 4 h of mechanical ventilation,lungs were removed for examination of pathological changes of lung tissues and for determination of wet/dry weight ratio (W/D ratio) and levels of pulmonary surfactant protein C (SP-C),xanthine oxidase (XOD) and glutathione reductase (GR) in lung tissues and broncho-alveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay.Results Compared with group C,the pathological score of lung tissues and W/D ratio were significantly increased,the levels of SP-C and GR in lung tissues and BALF were decreased,and the level of XOD in lung tissues and BALF was increased in H and D groups (P＜0.05).Compared with group H,the pathological score of lung tissues and W/D ratio were significantly decreased,the levels of SP-C and GR in lung tissues and BALF were increased,and the level of XOD in lung tissues and BALF was decreased in group D (P＜0.05).Conclusion Deferoxamine can inhibit oxidative stress response and alleviate hyperoxic lung injury in rats.

Effect of deferoxamine on ventilator-associated lung injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of deferoxamine on ventilator-associated lung injury in rats.Methods Twenty-four healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 250-300 g,were divided into 3 groups (n =8 each) using a random number table method:control group (group C),ventilator-associated lung injury group (group VALI),and ventilator-associated lung injury plus deferoxamine group (VALI+DFO group).Normal saline 2 ml was intraperitoneally injected in C and VALI groups,and deferoxamine 200 mg/kg (dissolved in 2 ml normal saline) was intraperitoneally injected in group VALI+DFO.The animals were connected to a small animal ventilator 15 min later and mechanically ventilated in volume-controlled mode,with tidal volume 40 ml/kg,respiratory rate 40-60 breaths/min,inspiratory/expiratory ratio 1 ∶ 1,and inspired oxygen fraction ratio 1.0.The rats were sacrificed after the end of mechanical ventilation,and the left lung tissues were removed for examination of the pathological changes (with a light microscope) which were scored and for determination of wet/dry weight ratio (W/D ratio).The right lung was lavaged,and lavage fluid was collected to prepare macrophage suspension,and the alveolar macrophage and mitochondrial reactive oxygen species (ROS) levels were determined using flow cytometry.Results Compared with group C,the pathological score,W/D ratio of lung tissues,and alveolar macrophage and mitochondrial ROS levels were significantly increased in group VALI,and the pathological score was significantly increased in group VALI (P＜0.05).Compared with group VALI,the pathological score,W/D ratio of lung tissues,and alveolar macrophage and mitochondrial ROS levels were significantly decreased in group VALI and DFO (P＜0.05).Conclusion Deferoxamine can reduce ventilator-associated lung injury,and the mechanism may be related to inhibiting oxidative stress in rats.

Deferoxamine synergizes with transforming growth factor-β signaling in chondrogenesis

Abstract Osteoarthritis, also known as degenerative arthritis or degenerative joint disease, is an epidemic disease that affects millions of people worldwide. Despite extensive recent work on the cellular biology of osteoarthritis, the precise mechanisms involved are still poorly understood and there is no effective treatment for this disease. The role of transforming growth factor-beta (TGF-β) in promoting chondrogenesis and inducing the expression of cartilage-specific extracellular matrix molecules to form cartilage is well-established. Historically, TGF-β has been considered to prevent osteoarthritis, but recent work suggests that TGF-β overexpression accelerates the progression of osteoarthritis in vivo. Clinically, it is therefore important to limit TGF-β expression while still providing effective treatment of osteoarthritis. One possible approach to achieve this effect would be to use a combination of TGF-β with other small molecular chemical compounds. Hypoxia promotes chondrogenesis and the usefulness of deferoxamine, a chelating agent that mimics hypoxia, in stimulating chondrogenesis has been investigated in clinical trials. In this study, we investigated the role of deferoxamine in TGF-β-induced chondrogenesis in pre-chondrogenic cells and examined whether deferoxamine synergizes with the TGF-β signaling pathway to promote chondrocyte differentiation.

Abnormal iron metabolism after intracerebral hemorrhage / 国际脑血管病杂志

Intracerebral Hemorrhage (ICH) is a common cerebrovascular disease with high disability rate and high mortality rate.A large number of clinical and experimental studies have shown that the abnormal metabolism of iron in the brain tissue around the hematoma after ICH is an important cause of secondary brain damage such as brain edema and neuronal apoptosis.It is an important factor affecting the outcome of patients.This article reviews the abnormal metabolism of iron and its significance after ICH.

Effect of TRPC6 after astrocytes activation in traumatic brain injury / 重庆医学

Objective To explore the role of astrocytes transient receptor potential channel 6(TRPC6) in rat brain injury (TBI).Methods Thirty-nine male Sprague-Dawley(SD) rats were divided into the sham operation group,injury group and deferoxamine(DFX) group(n=13).According to the previous model construction scheme established by our research group Feeney method,the rat brain impact injury model was established.The Morris water maze test was performed and the defected brain volume was measured.The immunofluorescence was adopted to detect the co-expression of TRPC6 and GFAP.Then Western blot was performed.Results The defected brain volume after TBI in the DFX group was significantly decreased compared with the injury group [(115.35 ± 13.70)mm3 vs.(209.99 ± 16.70)mm3]] (P＜0.05).The Morris water maze test found that the platform search strategy and search time in the DFX group were(3.13 ± 0.35) and(36.15 ± 26.63)s,which were significantly improve d compared with (2.13±0.64) and(110±47.34)s in the injury group(P＜0.05).The immunofluorescence found that GFAP in the DFX group was highly expressed,moreover the co-expression with TRPC6 was increased.Western blot found that TRPC6 in the DFX group was significantly down-regulated(P＜0.01).Conclusion In rat TBI early stage,strocytes are activated after DFX treatment and TRPC6 is highly expressed,playing a neuroprotective role.

Effect of simulated hypoxia on expression SOX2 and OCT4 of tongue squamous cell carcinoma SCC-15 cells / 第二军医大学学报

Objective To explore the effect of simulated hypoxic environment on proliferation, cell cycle, apoptosis and the protein and mRNA expressions of SOX2 and OCT4 in tongue squamous cell carcinoma SCC-15 cells. Methods SCC-15 cells was cultured in vitro, and the hypoxia mimetic agent desferrioxamine (DFO) was added to simulate hypoxic condition (simulated hypoxia group, HOX group) and normoxia was designed as control group (NOX group). CCK-8 assay was performed to measure the proliferation ability of the SCC-15 cells; flow cytometry was used to measure the apoptosis rate and cell cycle of the SCC-15 cells; Western blotting was applied to measure the expressions of HIF-1α, SOX2 and OCT4 protein in NOX and HOX groups; qPCR was used to measure the expressions of HIF-1α, SOX2 and OCT4 mRNA in NOX and HOX groups. Results DFO effectively simulated the hypoxic condition. Compared with the NOX group, the proliferation ability of the cells in HOX group was significantly inhibited by DFO (P0.05); the mRNA expressions of SOX2 and OCT4 in HOX group were significantly higher than those in NOX group (P<0.05). Conclusion DFO can effectively simulate hypoxic environment, and hypoxia can promote the expressions of SOX2 and OCT4 proteins and mRNA.

Efficacy of cold preservation solution containing desferrioxamine in protecting rat hearts / 中华麻醉学杂志

Objective To evaluate the efficacy of cold preservation solution containing desferrioxamine (DFO) in protecting the rat hearts.Methods Pathogen-free male Sprague-Dawley rats,weighing 300-350 g,were used in the study.Thirty-two isolated rat hearts were equally and randomly divided into control group (C group) and DFO group using a random number table.Hearts of rats were stored for 6 h in 4 ℃ histidine-tryptophan-ketoglutarate (HTK) solution in group C.DFO was added to HTK solution (DFO concentration 100 μmol/L),and hearts of rats were stored for 6 h in 4 ℃ HTK solution in group DFO.At 6 h of cold storage,creatine kinase and lactate dehydrogenase activities in the cold preservation solution were determined.Myocardial specimens were obtained from the apex,cut into sections which were stained with haematoxylin and eosin,and examined under a microscope.The pathological changes of myocardial tissues were scored.The content of malondialdehydc in myocardial tissues was determined using thiobarbitnric acid method,and hypoxia-inducible factor-1α protein and mRNA expression in myocardial tissues was detected by real-time reverse transcriptase polymerase chain reaction and Western blot.Results Compared with group C,the creatine kinase and lactate dehydrogenase activities in the cold preservation solution,malondialdehyde content in myocardial tissues,and pathological scores were significantly decreased,and the expression of hypoxia-inducible factor-1α protein and mRNA expression in myocardial tissues was significantly up-regulated in group DFO (P＜ 0.05).Conclusion Cold preservation solution containing DFO can protect the rat hearts effectively,and the mechanism is related to up-regulation of the expression of hypoxia-inducible factor-1α.

Effect of the deferoxamine mesylate on the prognosis of patients with intracerebral hemorrhage / 中国综合临床

Objective To study the effect of the deferoxamine mesylate on the prognosis of patients with intracerebral hemorrhage(ICH) after one year. Methods From February 2013 to May 2014,spontaneous ICH patients diagnosed by computed tomography ( CT ) within 18 hours of onset in Mancheng District Hospital of Baoding were evaluated. Patients were randomly divided into experimental group and control group. The treatment of the two groups was similar except that the experimental group received deferoxamine mesylate. Patients were e?valuated by CT and neurology scale( NIHSS scale,GCS scale) at the time of admission and followed up for the first year by the RANKIN( mRS) scale. All clinical data of the two groups were compared. Results Forty?two patients were included in the study, including 21 cases in the experimental group and 21 cases in the control group,there was no significant difference in baseline data between the two groups at admission. There were 6 pa?tients with mRS ≥3 in the experimental group, and 6 patients with mRS ≥3 in the control group after one year. There was no statistically significant difference in the distribution of mRS score between the two groups after one year admission( P=1. 000) . Conclusion There may be no helpful on the prognosis of patients with intrace?rebral hemorrhage by intravenous infusion of deferoxamine mesylate,the further study is needed.

Effect of deferoxamine on autophagy induction after blast-induced brain injury in rats / 中华创伤杂志

Objective To determine the effect of deferoxamine administration on autophagy in a rat model of blast-induced brain injury.Methods Thirty-nine male SD rats were allotted to shamoperated group,injury group and deferoxamine group with 13 rats in each,according to the random number table.Feeney's method was applied to establish the model.Deferoxamine group received deferoxamine of 100 mg/kg intraperitoneally.Sham-operated and injury group were injected with saline intraperitoneally.All treatments were started two hours postinjury at 12 hour interval for up to 28 days.Hemoglobin,rectal temperature,blood glucose and mortality were detected at 1,3,7,14 and 28 days.Morris water maze was conducted.Rats were killed later for detecting the brain defect volume and level of Beclin 1 at the site of injury.Results There were no significant differences among the three groups with respect to hemoglobin,rectal temperature and blood glucose (P ＞ 0.05).Mortality in injury versus deferoxamine groups did not differ significantly (P ＞ 0.05).Volume of defected brain in deferoxamine group was (115.35 ± 13.70) mm3,smaller than (209.99 ± 16.70) mm3 in injury group (P ＜ 0.05).In Morris water maze test,the time spent in the searching the platform and latency to reach the platform were improved in deferoxamine group compared to those in injury group [(3.13 ± 0.35) vs (2.13 ± 0.64);(36.15 ± 26.63) s vs (110 ± 47.34) s respectively] (P ＜ 0.05).Both immunohistochemisty and western blot showed dramatically increased level of Beclin 1 after injury,but treatment with deferoxamine significantly reduced the Beclin 1 expression.Conclusion Level of Beclin 1 is significantly upregulated after blast-induced brain injury in rats,resulting in elevated autophagy postinjury,but the treatment with deferoxamine is neuroprotective possible by lessening autophagy damage.