Disease relevance of Deferrioxamine B

• Intravenous or subcutaneous deferoxamine for iron overload [1]?
• Deferoxamine in thalassemia major [2].
• An analysis of the clinical data showed that members of the affected group were younger, had lower serum ferritin values, and were self-administering higher doses of deferoxamine per kilogram of body weight [3].
• Treatment of hemodialysis-related porphyria cutanea tarda with deferoxamine [4].
• Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major [5].

Psychiatry related information on Deferrioxamine B

• We conclude that sustained administration of desferrioxamine may slow the clinical progression of the dementia associated with AD [6].
• Although there was no relation between baseline psychomotor function and either indices of cumulative aluminium exposure or erythrocyte DHPR activity, changes in DHPR induced by desferrioxamine correlated with changes in psychomotor performance (r = 0.62) [7].
• Patient compliance with days of deferoxamine administration at follow-up was associated with initial compliance, perceived support, and patient and caregiver knowledge [8].
• However, the burden of prolonged subcutaneous portable pump infusions, high cost, and patient noncompliance have prompted the development of new methods of administration and new formulations of DFO as well as oral iron chelators [9].
• With deferoxamine treatment, only a minor increase in latency periods (4.5%) was detected after subarachnoid hemorrhage [10].

High impact information on Deferrioxamine B

• Five deferiprone-treated patients had progression of fibrosis, as compared with none of those given deferoxamine (P=0.04) [11].
• Of 19 patients in whom multiple biopsies were performed over a period of more than one year, 14 could be evaluated for progression of hepatic fibrosis; of the 20 deferoxamine-treated patients, 12 could be evaluated for progression [11].
• Ten patients in whom previous chelation therapy with deferoxamine had been ineffective had initial hepatic iron concentrations of at least 80 mumol per gram of liver, wet weight -- values associated with complications of iron overload [12].
• The risk of agranulocytosis associated with deferiprone may restrict its administration to patients who are unable or unwilling to use deferoxamine [12].
• The early use of deferoxamine in an amount proportional to the transfusional iron load reduces the body iron burden and helps protect against diabetes mellitus, cardiac disease, and early death in patients with thalassemia major [13].

Chemical compound and disease context of Deferrioxamine B

• To determine whether the orally active iron chelator deferiprone (1,2-dimethyl-3-hydroxy-pyridin-4-one) is efficacious in the treatment of iron overload in patients with thalassemia major, we conducted a prospective trial of deferiprone in 21 patients unable or unwilling to use standard chelation therapy with parenteral deferoxamine [12].
• The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) was compared with that of subcutaneous desferrioxamine in 26 patients with transfusional iron overload [14].
• METHODS: Heart homogenates from patients with valvular stenosis were tested for respiratory-chain complex II activity, lipoperoxidation, and aconitase activity by spectrophotometric assays, in the presence of reduced iron (Fe2+), oxidised iron (Fe3+), desferrioxamine, ascorbic acid, and idebenone [15].
• Cardioplegic arrest superimposed on evolving myocardial ischemia. Improved recovery after inhibition of hydroxyl radical generation by peroxidase or deferoxamine. A 31P nuclear resonance study [16].
• We report that treatment of Hep3B cells with desferrioxamine (DFX) induced HIF-1 activity and EPO RNA expression with kinetics similar to the induction of HIF-1 by hypoxia or cobalt chloride [17].

Biological context of Deferrioxamine B

• Significantly lower doses of deferoxamine were being taken by patients without abnormalities than by those with visual symptoms, abnormal audiograms, or prolonged evoked potentials (P less than 0.001, less than 0.006, and less than 0.04, respectively) [3].
• Beginning chelation treatment with deferoxamine before the age of puberty can help children with transfusion-dependent thalassemia major to attain normal sexual maturation [18].
• The half-life of NOS mRNA appeared not to be significantly altered by administration of ferric ion, and NOS mRNA stability was only slightly prolonged by desferrioxamine treatment [19].
• Both compounds activate NOS by limiting the availability of iron: their stimulating effects on NO synthesis and inhibiting action on cell proliferation are reverted by iron supplementation with ferric nitrilotriacetate, and are mimicked by incubation with desferrioxamine [20].
• These macromolecular forms of deferoxamine do not cause detectable decreases in blood pressure of experimental animals, even when administered intravenously in very large doses, and persist in circulation much longer than the free drug [21].

Anatomical context of Deferrioxamine B

• First, K562 (a cell line highly vulnerable to NK lysis) cells were grown for 24 h in the iron chelator desferrioxamine [22].
• Even without added fatty acids, degradation of ApoB100 in primary hepatocytes was blocked by desferrioxamine or antioxidant cotreatment [23].
• To determine if L. pneumophila intracellular multiplication is iron dependent, we studied the effect of the iron chelator deferoxamine on L. pneumophila infection of monocytes [24].
• Ten patients with excess body iron stores of different levels and with different diagnoses were given desferrioxamine inside osmotically lysed and resealed red blood cells (red cell ghosts) [25].
• Red cell ghost entrapped desferrioxamine was given intravenously and, ten days later, an equal dose of desferrioxamine was administered via slow subcutaneous infusion over 10 h [25].

Associations of Deferrioxamine B with other chemical compounds

• Furthermore, neither was the intracellular availability of the NOS cofactor tetrahydrobiopterin altered by treatment with Fe(3+) or desferrioxamine, nor do these compounds interfere with the activity of the hemoprotein NOS in vitro [19].
• To obviate this problem, we have covalently attached deferoxamine to high molecular weight carbohydrates such as dextran and hydroxyethyl starch [21].
• The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine [26].
• After one month of desferrioxamine, serum aluminium (including the chelate) had risen from 54.6 (SEM 11.2) to 167.0 (27.5) micrograms/l; and after three months haemoglobin had risen from 8.46 (0.70) to 10.43 (0.80) g/l. Mean cell volume and mean cell haemoglobin concentration also increased significantly [27].
• By introducing different combinations of oxygen metabolite-producing enzymes, xanthine oxidase, superoxide dismutase, and catalase, and an iron chelator, deferoxamine, to the fully confluent monolayers and to proliferating IEC-18 cells, the differential injurious effects of the oxygen metabolites O2-, H2O2, and OH. could be evaluated [28].

Gene context of Deferrioxamine B

• We further demonstrate that a hydroxylase inhibitor, hypoxia, and desferrioxamine promote the functional and physical interaction between HIF-1 alpha CAD and p300/CBP in vivo [29].
• Deferoxamine (DFO), an iron-chelating agent, up-regulated IFN-gammaR2 surface expression and reinstated IFN-gamma/STAT1 activation in proliferating T lymphocytes [30].
• In addition, treatment of cells with the iron chelator desferrioxamine also reduced MLH1 and PMS2 levels, in keeping with low oxygen tension being the stress signal that provokes the altered MMR gene expression [31].
• The involvement of HO. in the PGIS inactivation was supported by the fact that deferoxamine, pyrrolidinedithiocarbamate, DMSO, mannitol, and captopril antagonized the effect of IL-1beta on PGIS to different degrees [32].
• Of interest, p53R2 was 158-fold more susceptible to the iron chelator deferoxamine mesylate than hRRM2, although the iron content of the two proteins determined by atomic absorption spectrometer was almost the same [33].

Analytical, diagnostic and therapeutic context of Deferrioxamine B

• This study was designed to determine whether chelation therapy with deferoxamine before the age of puberty would ameliorate this problem [18].
• Treatment of transfusion-induced iron overload by daily intramuscular injection of the chelator desferrioxamine has not produced impressive urinary iron excretion [34].
• Coculture of Hc-infected Mphi with the iron chelator deferoxamine suppressed the growth of yeasts in a concentration-dependent manner [35].
• Subcutaneous desferrioxamine (2--4 g over 12 h) was administered 6 nights each week to 34 patients with transfusional iron overloads who continued to receive regular blood-transfusions [36].
• An intravenous infusion of desferrioxamine (3 g) was given to 17 chronic renal failure patients stabilised on standard haemodialysis [37].

References