Deferroxamine

The presence of microorganisms in biological fluids like urine and blood is an indication of vulnerability to infections. Iron is one of the important micronutrients required for bacterial growth. In an iron-deficit environment, bacteria release high-affinity iron-chelating compounds called siderophores which can be used as non-invasive target molecules for the detection of such pathogens. However, only limited reagents and procedures are available to detect the presence of these organic molecules. The present study aims at detecting the presence of siderophores in the iron-depleted media, exploiting the reversible quenching of Calcein Blue and iron(III) complex...

The effects of hypoxia and perfluorooctane sulfonamide (PFOSA), given singly and also in combination on endocrine, biotransformation, and oxidative stress responses were investigated in primary culture of salmon hepatocytes. Hypoxia was induced chemically using cobalt chloride (CoCl2) or deferroxamine (DFO). Primary culture of salmon hepatocytes were exposed to either CoCl2 (150 μM) or DFO (100 μM), in the presence or absence of PFOSA at 0, 25, and 50 μM for 24 and 48 h. Changes in transcript levels were analyzed by quantitative (real-time) PCR using gene-specific primers...

The relative importance of environmental hypoxia due to global climate change on organismal ability to adapt to chemical insult and/or mechanisms of these responses is not well understood. Therefore, we have studied the effects of combined exposure to perfluorooctane sulfonamide (PFOSA) and chemically induced hypoxia on membrane lipid profile and homeostasis. Primary salmon hepatocytes were exposed to PFOSA at 0, 25 and 50 µM singly or in combination with either cobalt chloride (CoCl2: 0 and 150 µM) or deferroxamine (DFO: 0 and 100 µM) for 24 and 48 h...

Filamentous fungi are an important cause of pulmonary and systemic morbidity and mortality, and also cause corneal blindness and visual impairment worldwide. Utilizing in vitro neutrophil killing assays and a model of fungal infection of the cornea, we demonstrated that Dectin-1 dependent IL-6 production regulates expression of iron chelators, heme and siderophore binding proteins and hepcidin in infected mice. In addition, we show that human neutrophils synthesize lipocalin-1, which sequesters fungal siderophores, and that topical lipocalin-1 or lactoferrin restricts fungal growth in vivo...

Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis. The guidelines were developed using the evidence criteria set forth by the American Infectious Diseases Society and the key recommendations are summarized here...

The differentiation of myelin-forming Schwann cells (SC) is completed with the appearance of myelin proteins MBP and P(0) and a concomitant downregulation of markers GFAP and p75NTR, which are expressed by immature and adult non-myelin-forming SC. We have previously demonstrated that holotransferrin (hTf) can prevent SC dedifferentiation in culture (Salis et al., 2002), while apotransferrin (aTf) cannot. As a consequence, we used pure cultured SC and submitted them to serum deprivation in order to promote dedifferentiation and evaluate the prodifferentiating ability of ferric ammonium citrate (FAC) through the expression of MBP, P(0), p75NTR and c-myc...

The metabolic profile of Streptomyces sp. strain C34, isolated from the Chilean hyper-arid Atacama Desert soil, is dependent on the culture media used for its growth. The application of an OSMAC approach on this strain using a range of cultivation media resulted in the isolation and identification of three new compounds from the rare class of 22-membered macrolactone polyketides, named chaxalactins A-C (1-3). In addition, the known compounds deferroxamine E (4), hygromycin A (5), and 5″-dihydrohygromycin A (6) were detected...

Rhino-orbital mucormycosis is an uncommon and aggressive, angioinvasive fungal infection that occurs in immunocompromised states like diabetes mellitus, chronic renal failure, hematological malignancies and deferroxamine therapy. We report a patient who presented with rhino-orbital mucormycosis at six months of gestation and was incidentally detected to have diabetes. She was successfully treated with amphotericin B and appropriate surgery. To the best of our knowledge, there is no such report in the literature...

AIM: Diabetic peripheral artery disease (PAD) is prone to be aggressive and recent reports have demonstrated that p53 accumulation may be responsible for impaired wound healing in diabetes. Statins has been demonstrated to facilitate p53 degradation by activating its specific ubiquitin ligase, MDM2. The aim of this study was to determine whether atorvastatin (ATR) improves the outcome of diabetic PAD through MDM2-mediated reduction of p53. METHODS: Male KK/Ay mice (9 weeks old) were treated with ATR (2 mg/kg/day p...

Iron overload resulting from transfusion dependency in some patients with chronic anaemia can be prevented by chelation. Deferasirox is an oral alternative to the well studied but inconvenient deferroxamine therapy. The pharmacokinetic parameters of this new drug suggest potential interindividual variability and patients might benefit from pharmacologic drug monitoring. We developed an liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) method to quantify deferasirox in plasma. After protein precipitation, samples were injected onto an XTerra RP18 column with a gradient of acetonitrile and formiate buffer (4 mM, pH 3...

PURPOSE: The improvement of regeneration and functional recovery after peripheral nerve injury is a major challenge in neurosurgery. Although microsurgical techniques for nerve reconstruction have seen great advancements over the last years, the clinical outcome with patients is often unsatisfactory. The aim of the present study was to investigate if administration of the iron chelator Deferroxamine (DFO), can improve postoperative outcome in the rat median nerve reconstruction model...

Cross-talk between the two transcription factors, p53 and hypoxia inducible factor 1alpha (HIF1A), is important in different pathophysiological conditions (Hammond and Giaccia, 2006, Clin Cancer Res 12:5007-5009) such as in the transition from myocardial hypertrophy to cardiac dilatation and heart failure. In that context, p53 induces HIF1A degradation which in turn provokes the transition from compensatory hypertrophy to myocardial thinning and chamber dilatation (Sano et al., 2007, Nature 446:444-448). In order to investigate the mechanism of p53-induced HIF1A degradation, we used the established in vitro model of deferroxamine (DFX)-induced HIF1A accumulation in H9c2 cardiac cells (Sano et al...

The mature human erythrocyte, when submitted to oxidative stress, can demonstrate depletion of reduced glutathione, oxidation of the hemoglobin molecule and aggregation of complexes of iron close to the membrane. These can produce abnormalities in the erythrocyte membrane and hemolysis. The aim of this work was to study the antioxidative action of vitamin C (vit. C), deferroxamine (DFO) and the flavonoids quercetin and rutin in normal human erythrocytes, submitted to in vitro oxidative stress induced by tert-butylhydroperoxide ((t)BHP)...

OBJECTIVE: "Ischemic tolerance" can be induced in the retina by "preconditioning" with brief periods of non-injurious retinal ischemia or systemic hypoxia. The present study was undertaken to assess whether tolerance can be induced pharmacologically by deferroxamine (DFX), an iron chelator, which promotes the expression of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1alpha), and to identify potential HIF-1alpha -induced effectors of this endogenous protective response...

Previous work showed that dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary artery hypertension in rat via targeting smooth muscle cells. In our study, DHEA was tested on human pulmonary arterial smooth muscle cells (HPASMC) to identify its mechanism of action under hypoxia in vitro. We show that DHEA decreased HIF-1alpha accumulation under both "chemical hypoxia" with treatment by the iron chelator deferroxamin and gas hypoxia (1% O2). The mRNA levels of HIF-1alpha were unchanged whether or not DHEA was applied under chemical and gas hypoxia, as compared to controls in normoxia, suggesting a post-transcriptional effect of the steroid...

Recently, we reported that the transient expression of huntingtin exon1 polypeptide containing polyglutamine tracts of various sizes (httEx1-polyQ) in cell models of Huntington disease generated an oxidative stress whose intensity was CAG repeat expansion-dependent. Here, we have analyzed the intracellular localization of the oxidative events generated by the httEx1-polyQ polypeptides. Analysis of live COS-7 cells as well as neuronal SK-N-SH and PC12 cells incubated with hydroethidine or dichlorofluorescein diacetate revealed oxidation of these probes at the level of the inclusion bodies formed by httEx1-polyQ polypeptides...

Sulfate-reducing bacteria (e.g. Desulfotomaculum acetoxidans) exist in animal intestine. These bacteria are able to bind heavy metals (e.g. cadmium or lead). Comparative investigations on the composition of cellular walls of Desulfotomaculum acetoxidans--depending on the initial Fe2+ supplement in the medium (7.5, 57.5 and 507.5 M) were performed. Iron(II) was cumulated as FeS or as pyrite (FeS2). However, if the initial amount of iron was higher, its majority (46% 85%) was transported onto the membrane. It was determined that the siderophore found in Desulfotomaculum acetoxidans was deferroxamine as in animals...

Ascorbic acid (AA) is one of the most important endogenous reducing agents and can participate in a variety of cellular events. In vitro, AA can act as a potent oxidant agent in the presence of free metals, promote modifications in protein structures and form reactive oxygen species during its oxidation. We have observed that AA (above 6 mmol/l) inactivates delta-aminolevulinate dehidratase (delta-ALA-D), a sulfhydryl-containing enzyme and that the inhibitory action was considerably decreased when 3-morpholinepropanesulfonic acid buffer (MOPS - pH: 6...

Iron overload and enhanced hydroxyl radical (*OH) formation have been implicated as the causative factors of oxidative stress in different organs. Both pro-oxidant and anti-oxidant properties have been reported for nitric oxide (NO) in iron-mediated tissue injury. To determine the contribution of NO to iron-induced renal injury, eight groups of rats (eight in each group) were studied as follows: control (normal saline), L-Arg (L-arginine as a substrate of NO synthase, 400 mg/kg), L-NAME (an inhibitor of NO synthase, 8 mg/kg), Fe (iron dextran, 600 mg/kg), DFO (deferroxamine as a chelator of iron, 150 mg/kg), Fe+L-Arg, Fe+L-NAME, DFO+L-Arg...

In a previous report, we characterized several oxidative stress parameters during the course of amyloid beta (Abeta) peptide/Fe2+-induced apoptotic death in neuronal cells. In extending these findings, we now report a marked decrease in protein kinase C (PKC) isoforms, reduced Akt serine/threonine kinase activity, Bcl 2-associated death promoter (BAD) phosphorylation and enhanced p38 mitogen-activated protein kinase (MAPK) and caspase-9 and -3 activation, 12 h after addition of both 5 micro m Abeta and 5 micro m Fe2+...