Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Deferoxamine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources
PubMed1989

Free radicals mediate peroxidative damage in guinea pig hippocampus in vitro.

Previous studies have shown that peroxide caused electrophysiological damage. The present study investigates the action of agents that interfere with a free radical process in an effort to define the mechanism of peroxide damage. Deferoxamine chelates iron, making it unavailable for the Fenton reaction and thereby preventing the formation of hydroxyl free radicals from peroxide. Dimethylsulfoxide (DMSO) scavenges hydroxyl free radicals. Trolox-C, a water soluble Vitamin E analog, is an antioxidant that can scavenge peroxy radicals. Slices of hippocampus were removed from brains of euthanized guinea pigs. Electrical stimulation of an orthodromic pathway to CA1 region evoked a synaptic response and a population spike. Input-output curves were generated to evaluate the protection by deferoxamine, Trolox-C, and DMSO on the synaptic damage and impaired spike generation caused by peroxide. Lipid peroxidation was measured by the thiobarbituric acid test. Peroxide was found to increase lipid peroxidation. Deferoxamine and Trolox-C protected against the peroxide-induced synaptic damage, impaired spike generation, and lipid peroxidation. DMSO was ineffective synaptically but reduced peroxide damage to spike generating mechanisms and further lipid peroxidation. The data support the hypothesis that peroxide causes damage through a free radical mechanism.

Action Potentials↗
PubMed1993

Role of superoxide and trace transition metals in the production of alpha-hydroxyethyl radical from ethanol by microsomes from alcohol dehydrogenase-deficient deermice.

The formation of alpha-hydroxyethyl radical from ethanol by deermouse microsomes supplemented with NADPH has been demonstrated with the EPR technique of spin trapping with alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN) as the spin trap, in the presence of deferoxamine mesylate. Superoxide dismutase prevented the formation of the radical adduct of the alpha-hydroxyethyl radical in a dose-dependent fashion, causing complete inhibition of radical formation at a concentration of 20 micrograms/ml, while catalase, azide, or azide and hydrogen peroxide had no effect. Boiling the microsomes or omission of NADPH abolished free radical formation. Metyrapone, cimetidine, isoniazid, octylamine, and p-nitrophenol, inhibitors of cytochrome P450IIE1 activity, decreased free radical formation by 24 to 74% at concentrations ranging from 0.05 to 10 mM. The POBN/.CH(OH)CH3 radical adduct signal was also diminished by formate or mannitol, indicating competition by so-called "hydroxyl radical scavengers. "The involvement of trace transition metals in alpha-hydroxyethyl radical formation by deermouse microsomes was demonstrated by a decrease in free radical adduct signal when metal ions were removed from reagents by treatment with Chelex 100 resin. Chelex treatment was effective even though the metal chelator deferoxamine mesylate, which is generally presumed to render iron catalytically inactive, was present in all incubations. Thus, it is concluded that free radical formation from ethanol in deermouse microsomes is mediated by a transition metal- and cytochrome P450-derived superoxide-dependent oxidizing species even in the presence of deferoxamine mesylate.

Alcohol Dehydrogenase↗
PubMed1994

Different mechanisms of tert-butyl hydroperoxide-induced lethal injury in normal and tumor thymocytes.

Normal thymocytes and thymoma cells have been exposed to the toxic action of tert-butyl hydroperoxide (t-BOOH) to study the mechanisms of oxidative lethal cell injury and the sensitivity of normal and tumor cells to an oxidative stress. From our data, we can suggest that: (a) In thymoma cells two mechanisms can operate in determining t-BOOH toxicity: the first one, involving glutathione peroxidase and nicotinamide nucleotides, leads to cell death by alteration of calcium homoeostasis, and the second one, involving potent oxygen reactive species, affects cell viability by ATP depletion. The first mechanism is demonstrated by the decrease of nicotinamide nucleotides, the partial protection from lactate dehydrogenase (LDH) release by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) (40%) and by dithiothreitol (DTT) (52%). The second mechanism is based on the partial protection of LDH release by deferoxamine (42%) and glucose (50%) and by total protection of ATP depletion by glucose. In agreement with these observations, DTT and deferoxamine in combination totally prevent cell death as well as EGTA and glucose do. (b) In normal thymocytes only the mechanism involving oxygen radical species is implicated. t-BOOH-induced death is not related to modifications of nicotinamide nucleotide pool. No changes are observed in LDH release by the addition of EGTA and DTT. In contrast, deferoxamine totally prevents cell death. Mechanisms depending on cellular ATP are involved in t-BOOH-induced oxidative damage. Glucose completely prevents t-BOOH-mediated ATP depletion and completely protects from LDH release. Our data indicate that tumor transformation deeply affects cell properties and metabolism, changing cell responsiveness to an oxidative stress.

Adenosine Triphosphate↗
PubMed1997

Synthesis of Cr(IV)-GSH, its identification and its free hydroxyl radical generation: a model compound for Cr(VI) carcinogenicity.

Current models of Cr(VI) carcinogenesis suggest an important role for Cr(IV) as an intermediate, toxic, carcinogenic species, but direct chemical evidence has been lacking. This is because Cr(IV) is a highly reactive oxidation state of Cr and few Cr(IV)-based compounds are known that can be used as a model compound containing a biological ligand. This study reports the isolation of such a stable Cr(IV) complex. The Cr(IV)-GSH complex has been synthesized through the reaction of Cr(VI) with GSH. Its electron paramagnetic resonance (EPR) spectrum exhibits g = 1.9629 and a peak-to-peak line width of 480 G in aqueous medium as well as in the powder form. Magnetic susceptibility measurements showed that the compound has a magnetic moment of 2.53 Bohr magneton per Cr, establishing that the Cr ion has two unpaired electrons, hence its identity as Cr(IV). The Cr(IV)-GSH complex is able to generate hydroxyl (.OH) radical in the presence of molecular oxygen in aqueous medium. Catalase inhibited the .OH radical generation while H2O2 enhanced it, indicating that the .OH radical was generated via a Fenton-like reaction, H2O2 being generated as an intermediate in the reduction of molecular oxygen. Metal ion chelators, deferoxamine and 1,10-phenanthroline, attenuated the generation of Cr(IV)-mediated .OH radical. In the case of deferoxamine, a deferoxamine-derived free radical was generated as shown by EPR measurements. The results imply that Cr(IV) may play an important role in the mechanism of Cr(VI)-induced carcinogenesis and Cr(IV)-GSH can be used as a model compound to study the role of Cr(IV) in this mechanism.

Carcinogens↗
PubMed1997

The efficacy of antioxidants administered during low temperature storage of warm ischemic kidney tissue slices.

Accumulation of products of lipid peroxidation (malondialdehyde, conjugated dienes, lipid peroxides, and Schiff bases) was evaluated in rabbit kidney cortex slices made ischemic for 60 min followed by 18 h storage at 5 degrees C in UW Na gluconate solution and 210 min normothermic reoxygenated incubation. In addition, the effect of adding Trolox (1 mM), deferoxamine (1 mM), and ascorbate (1 mM) as supplemental antioxidants to the UW gluconate solution was evaluated. Lipid peroxidation was slightly increased after hypothermic storage compared to slices subjected to ischemia alone but was not significantly different than ischemic slices during subsequent incubation at normothermia. The addition of either deferoxamine or Trolox to the storage solution substantially reduced lipid peroxidation both during hypothermic storage and subsequent to normothermic incubation. Ascorbate had a mild prooxidant effect as a sole additive to the UW gluconate solution but was clearly prooxidant when combined with either deferoxamine or Trolox. These results suggest that supplemental antioxidants added to the UW gluconate solution under conditions analogous to machine perfusion preservation have a potential role in reducing oxidative stress in kidney tissues harvested after warm ischemia and that hypothermia may be a valuable adjunct to resuscitative therapeutic regimens developed for salvage of ischemic kidneys for transplantation.

Animals↗
PubMed2003

Redox state of near infrared spectroscopy-measured cytochrome aa(3) correlates with delayed cerebral energy failure following perinatal hypoxia-ischaemia in the newborn pig.

Early detection of delayed cerebral energy failure may be important in the prevention of reperfusion injury of the brain after severe perinatal hypoxia-ischaemia (HI). This study investigated whether monitoring of the redox state of cytochrome aa(3) (Cytaa(3)) with near infrared spectroscopy (NIRS) after severe perinatal asphyxia may allow us to detect early a compromised energy metabolism of the developing brain. We therefore correlated serial Cytaa(3) measurements (to estimate mitochondrial oxygenation) simultaneously with the (31)phosphorous-magnetic resonance spectroscopy ((31)P-MRS)-measured phosphocreatin/inorganic phosphate (PCr/Pi) ratio (to estimate cerebral energy reserve) in newborn piglets before and after severe hypoxia-ischaemia. The animals were treated upon reperfusion with either allopurinol, deferoxamine, or 2-iminobiotin or with a vehicle to reduce post-HI reperfusion injury of the brain. Four sham-operated piglets served as controls. Before HI, the individual Cytaa(3) values ranged between -0.02 and 0.71 micromol/L (mean value: -0.07) relative to baseline. The pattern over post-HI time of the vehicle-treated animals was remarkably different from the other groups in as far Cytaa(3) became more oxidised from 3 h after start of HI onwards (increase of Cytaa(3) as compared with baseline), whereas the other groups showed a significant reduction over time (decrease of Cytaa(3) as compared with baseline: allopurinol and deferoxamine) or hardly any change (2-iminobiotin and sham-operated piglets). Vehicle-treated piglets showed a significant reduction in PCr/Pi at 24 h after start of HI, but the cerebral energy state was preserved in 2-iminobiotin-, allopurinol- and deferoxamine-treated piglets. With severe reduction in PCr/Pi-ratio, major changes in the redox-state of Cytaa(3) also occurred: Cytaa(3) was mostly either in a reduced state (down to -6.45 micromol/L) or in an oxidised state (up to 6.84 micromol/L) at these low PCr/Pi ratios. The positive predictive value (PPV) of Cytaa(3) to predict severe reduction of the PCr/Pi ratio was 42%; the negative PPV was 87%. A similar relation was found for Cytaa(3) with histologically determined loss of neurons.

Allopurinol↗
PubMed1991

Effects of platelet-activating factor antagonist CV-3988 in preservation of heart and lung for transplantation.

The preservation of heart and lung for transplantation remains a major concern in extended ischemic intervals. This experiment evaluated the effect of high molecular weight deferoxamine and a platelet-activating factor antagonist (CV-3988) in ischemic reperfused tissue. Heart-lung transplantation was performed in a swine model after 4 hours 45 minutes of ischemia. Animals were divided into three groups. Group A was a control without pharmacological intervention. In group B, high molecular weight deferoxamine, 50 mg/kg, was used, and in group C, platelet-activating factor antagonist CV-3988, 10 mg/kg, was used. The results of functional variables (cardiac index, stroke index, lung water, oxygen and carbon dioxide tensions, alveolar-arterial gradient, and alveolar-arterial ratio) demonstrated superior heart and lung function for groups B and C compared with the control group. These alterations of heart and lung function were significantly less (p less than 0.001) in group C, in which the platelet-activating factor antagonist (CV-3988) was used. The study revealed that formation of hydroxyl radicals and platelet-activating factor play an important role in the pathogenesis of ischemia reperfusion injury. Prevention of hydroxyl radical formation with high molecular weight deferoxamine and inactivation of platelet-activating factor with CV-3988 reduce the ischemia-reperfusion injury significantly.

Animals↗
PubMed1992

Generation of hydroxyl radical by crocidolite asbestos is proportional to surface [Fe3+].

Differences among fibrous silicates to effect injury in biological systems have been postulated to reflect oxidant generation by structural iron within the crystal lattice of amphiboles. Iron is also coordinated to the surface of all silicates in concentrations which depend on the density of acidic functional groups. We tested the hypothesis that oxidant generation by crocidolite is proportional to surface-complexed iron rather than variance in the lattice concentrations of this transition metal. Surface iron was quantified after its reduction to Fe2+ and chelation by citrate. Thiobarbituric acid (TBA) reactive products and dihydroxybenzoic acid products of salicylate were employed as indices of nonspecific oxidant and hydroxyl radical generation, respectively. Surface iron, TBA reactive products, and dihydroxybenzoic acid products all diminished after pretreatment of crocidolite with the metal chelator deferoxamine in concentrations varying from 0 to 250 mM. Inclusion of deferoxamine in the reaction mixture provided similar results of diminishing both TBA reactive products and dihydroxybenzoic acid generation. We conclude that oxidant generation by crocidolite is proportional to surface concentrations of iron which can be chelated using deferoxamine. The design of synthetic fibers without health effects after exposure will likely necessitate decreasing the number of surface acidic functional groups to diminish the capacity to complex iron (i.e., minimize the percentage SiO2).

Asbestos↗
PubMed1985

Lysosomal origin of the ferric iron required for cell killing by hydrogen peroxide.

The lysosomotropic amines methylamine (40 mM) and chloroquine (125 mM) prevented the killing of cultured hepatocytes by hydrogen peroxide generated in the medium by glucose oxidase. Maximum protection required several hours preincubation with either amine. Sensitivity of the hepatocytes to H2O2 was restored either by the addition of ferrous or ferric iron to the culture medium, or by incubating the cells for 4 hours in the absence of either amine prior to treatment with H2O2. Neither methylamine nor chloroquine had any effect on the cell killing by t-butyl hydroperoxide, a hepatotoxin that does not require iron. The protective effect of the lysosomotropic amines was distinguished from that of the ferric iron chelator deferoxamine in two ways: 1) deferoxamine protected hepatocytes from H2O2 toxicity but did not require a pretreatment period; and 2) in contrast to methylamine or chloroquine, deferoxamine had no effect on lysosomal pH as assessed by the fluorescent probe acridine orange. The data suggest that a lysosomal pool is the source of the ferric iron necessary for the killing of hepatocytes by H2O2.

Animals↗
PubMed1993

Aggregation of tau protein by aluminum.

Aluminum has been detected in Alzheimer neurofibrillary tangles, but the significance of its presence is unknown. The principal component of tangles is the paired helical filament (PHF), comprised of tau protein. We investigated whether aluminum could induce tau protein to form filaments or aggregate. When 10 microM bovine tau or non-phosphorylated recombinant human tau was combined with 400 microM or more aluminum, tau protein appeared to aggregate, observed as a dose-dependent decrease in electrophoretic mobility on SDS-PAGE. Tau appeared as a smear above the region of the expected tau bands and, at higher aluminum doses, failed to enter the gel. A tau fragment encompassing the microtubule binding domains did not show decreased mobility in the presence of aluminum, but did form aggregates that failed to electrophorese. However no fibrillar structures were observed in the aluminum-treated tau samples when observed by electron microscopy. The effect of aluminum on tau mobility was reversed by incubating with 1 mM deferoxamine. In contrast, the morphology of PHF fibrils was unaffected by deferoxamine treatment and the characteristic abnormal mobility of PHF-tau was not reduced by deferoxamine. This suggests that aluminum is not, by itself, a significant factor in maintaining the assembly of PHF-tau as fibrils or in its abnormal mobility on SDS gels. Aluminum treatment of 3T3 fibroblasts transfected with human tau resulted in toxicity, but did not change tau expression levels or induce tau aggregation. In conclusion, aluminum appears to induce isolated tau protein to aggregate in a phosphate-independent way, without the formation of fibrils.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1990

Role of O2- in neutrophil recruitment into sites of dermal and pulmonary vasculitis.

Using analogous models of acute dermal vasculitis and alveolitis in rats, we have examined the role of oxygen-derived metabolities in the tissue damage associated with neutrophil influx into sites of immune complex deposition. In the lung, as previously reported, catalase and deferoxamine are highly protective, while superoxide dismutase (SOD) has a transient protective effect. The xanthine oxidase inhibitors, allopurinol, and lodoxamide, are also protective. In the skin, neither catalase (which has been covalently linked to the antibody) nor deferoxamine is protective, suggesting that H2O2 and iron are not absolutely required for the development of dermal vasculitis. In the skin, SOD, as well as the inhibitors of xanthine oxidase, have protective effects. These data suggest that the neutrophil-mediated pathways of immune complex injury in the dermal and pulmonary microvascular compartments are fundamentally different. As a measurement of neutrophil accumulation, measurements of myeloperoxidase in tissue extracts have been employed. In both the lung and skin, the protective effects of SOD and the xanthine oxidase inhibitors are paralleled by reductions in neutrophil influx into sites of injury. In contrast, catalase and deferoxamine have no effect on neutrophil accumulation. These data suggest that vascular beds in rat skin and lung are fundamentally different with respect to mechanisms of acute immune complex mediated injury. The data also provide evidence that O2- contributes significantly to the accumulation of neutrophils.

Allopurinol↗
PubMed2005

Iron-chelating therapy with the new oral agent ICL670 (Exjade).

Iron-chelation therapy is essential in iron-overloaded patients. The long-term efficacy of this approach has been demonstrated unequivocally with deferoxamine, which effectively controls iron concentrations, thereby limiting organ damage and preventing premature death. However, as deferoxamine is administered parenterally, poor compliance is a significant limitation to successful patient management. ICL670 (Exjade) is a highly efficient and selective oral iron chelator. The results of phase I and phase II clinical studies indicate that ICL670 is at least as effective as current standard therapy (deferoxamine), with a tolerability and safety profile suitable for chronic, once-daily administration. These encouraging results have provided the rationale for the ongoing phase III programme, and offer physicians and patients the promise of an oral, once-daily, iron-chelating agent for the prevention and management of iron overload.

Administration, Oral↗
PubMed2005

Iron-mediated stability of PAI-1 mRNA in adenocarcinoma cells-involvement of a mRNA-binding nuclear protein.

This study reports the stability of mRNA of type-1 plasminogen activator inhibitor (PAI-1), the major physiologic inhibitor of plasminogen activation, by deferoxamine-aided iron deprivation, in PC3 adenocarcinoma cells. ELISA and Northern analyses studies revealed dose-dependent increase in PAI-1 expression by deferoxamine-treated cells. Co-treatment with ferric citrate quenched the effect of deferoxamine, confirming the role of iron in PAI-1 regulation. DRB-based RNA chase experiments suggested that post-transcriptional mechanism was involved in PAI-1 regulation. De-novo protein synthesis was necessary for this regulation. Electrophoretic mobility shift assay revealed the presence of a nuclear protein, binding to the 3'-UTR of PAI-1 mRNA in an iron-mediated manner. This is the first report of iron-mediated mRNA-protein interaction in PAI-1, involved in mRNA stability.

3' Untranslated Regions↗
PubMed1997

Cardiopulmonary bypass alters vasomotor regulation of the skeletal muscle microcirculation.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with alterations in the regulation of organ perfusion and vascular permeability. The purpose of this study was to examine the effects of hypothermic CPB on the regulation of the skeletal muscle microcirculation and the modulating influence of the priming solution. METHODS: Sheep were placed on hypothermic CPB with a prime of either Pentastarch hydroxylethyl starch (HS) solution (n = 7), a solution in which HS is conjugated with deferoxamine (n = 7), or Ringer's lactate solution (n = 7). Sheep were placed on hypothermic CPB (27 degrees C) for 90 minutes while the heart was protected with cold blood cardioplegia. Sheep were then separated from CPB and perfused for an additional 3 hours off CPB. Hemodynamics and total water content were measured. RESULTS: In vitro relaxation responses of gracilis muscle arterioles (70 to 180 microns) to the endothelium-dependent agent acetylcholine, the endothelium-independent cyclic GMP-mediated vasodilator sodium nitroprusside, the beta-adrenergic agonist isoproterenol, and the adenylate cyclase activator forskolin were studied. No statistically significant hemodynamic differences were observed between groups. However, weight gain was significantly less when the priming solution was HS or HS-deferoxamine compared to when Ringer's lactate was used. Skeletal muscle arteriolar relaxations to the endothelium-dependent vasodilator acetylcholine and the beta-adrenergic agonist isoproterenol were impaired after CPB in the HS and Ringer's lactate groups. Acetylcholine response was preserved in the HS-deferoxamine group, whereas the response to isoproterenol remained impaired. The responses to sodium nitroprusside and forskolin were similar in all groups. CONCLUSIONS: Skeletal muscle microvascular endothelium-dependent relaxation and beta-adrenergic relaxation are reduced after CPB using either a crystalloid or HS prime. Skeletal muscle microvascular endothelial dysfunction may be attributable to oxygen-derived free radical-mediated injury, whereas altered beta-adrenergic regulation is attributable to mechanisms other than the generation of oxygen-derived free radicals during CPB.

Acetylcholine↗
PubMed1981

Chelation therapy in beta-thalassemia major. III. The role of splenectomy in achieving iron balance.

Transfusion requirements for 1978 were compiled for 79 patients with thalassemia major (ages 1 to 29 years) who were maintained at hemoglobin concentrations of greater than 10 gm/dl. In 46 patients with intact spleens, the mean transfusion requirement was 258 ml/kg/year, and there was a clear increase with age. The transfusion history prior to 1978 had no influence on the increase of transfusion requirement with age. In contrast, in 33 splenectomized patients, the mean transfusion requirement was 203 ml/kg/year and it did not increase with age. Urinary iron excretion in response to deferoxamine increased with age, with no obvious difference between splenectomized and nonsplenectomized patients. The ability to achieve iron balance with a daily dose of 20 mg/kg of deferoxamine was a function of the transfusion requirement splenectomized patients with lower blood requirements generally achieved negative iron balance, whereas nonsplenectomized patients did not. We conclude that the spleen should be removed when the transfusion requirement exceeds 250 ml/kg/year, which usually occurs between 6 and 8 years of age. In young patients with intact spleens, a higher dose of deferoxamine may be use in order to prevent hemosiderosis.

Adolescent↗
PubMed1989

Rapid removal of excessive iron with daily, high-dose intravenous chelation therapy.

We investigated the value of high-dose intravenous iron chelation therapy with deferoxamine as an alternative to conventional subcutaneous therapy in eight patients receiving regular transfusions who had massive iron stores, including two with clinical heart disease. Six to twelve grams of deferoxamine was infused daily for 12 hours over 12 to 25 months through externalized central venous catheters or implanted reservoirs. Serum ferritin levels decreased by 56% to 99%. Liver iron concentrations, measured by magnetic susceptibility in two patients, were 1234 and 2438 micrograms/gm wet weight (22.1 and 43.6 mumol/gm wet weight) after treatment for 17 and 25 months, respectively. A patient with congestive heart failure and a patient with severe ventricular dysrhythmias no longer required cardiac medication after 12 to 24 months of chelation therapy. Three episodes of bacteremia and three episodes of cellulitis accounted for a catheter-related infection rate of 0.14 per 100 patient-days. The catheter removal rate was 0.20 per 100 patient-days. No patient experienced serious visual, auditory, or other toxicities. We conclude that in some patients receiving regular erythrocyte transfusions, high-dose intravenous chelation therapy with deferoxamine is superior to conventional subcutaneous treatment.

Adolescent↗
PubMed1997

Antineoplastic drugs that interfere with iron metabolism in cancer cells.

Normal iron metabolism can be perturbed with iron chelators, toxic metals that bind to transferrin, toxic metals bound to transferrin or antineoplastic agents covalently linked to transferrin. These agents cause significant inhibition of tumor cell growth in cell culture and have been shown to have significant in vivo antineoplastic activity. Cell culture studies showed that deferoxamine mesylate inhibits cell growth and division in both the MCF-7 human breast and HeLa human cervical carcinoma cell lines. Animal studies demonstrated that when deferoxamine mesylate is injected intravenously into rats that are on a low iron diet, there is a significant reduction in the growth of 13762NF mammary adenocarcinomas. Gallium, indium and the antineoplastic agent cisplatin were bound to the iron binding site of transferrin and inhibit the growth of malignant carcinoma cell lines. Gallium-transferrin and indium-transferrin were at least 10 times more inhibitory to both MCF-7 and HeLa cell lines than their free salts. Further cell culture studies demonstrated that cisplatin-transferrin complexes act synergistically with doxorubicin to inhibit the growth of cultured MCF-7 cells. In a Phase I clinical trial of cisplatin-transferrin complex there was a 36% (four of 11 patients) response rate in breast cancer patients with advanced disease. In a second clinical study the sequential administration of deferoxamine mesylate (2 days at 6 g/day in 8 hrs), cisplatin-transferrin complex (7 days at 500 mg/day) and FAC (5-fluorouracil, doxorubicin and cyclophosphamide at 450, 45 and 450 mg/m2, respectively) to advanced breast cancer patients resulted in partial responses in seven of eight patients treated. Future work will concentrate on substituting transferrin based agents with daunorubicin or doxorubicin attached to the surface of the transferrin, and gallium or indium bound to the iron binding site, to increase efficacy of the second component of the sequential combination chemotherapy.

Animals↗
PubMed1997

Water-soluble fullerene derivatives attenuate exsanguination-induced bronchoconstriction of guinea-pigs.

1. This study investigated the effects of increased antioxidants (administration of water-soluble fullerenol-1 and pre-exposure to chronic hypoxia) as well as an iron-chelating agent (deferoxamine) on exsanguination-induced noncholinergic airway constriction in guinea-pigs. 2. Fullerenol-1 usually did not cause significant alteration in respiratory function (lung volumes, dynamic respiratory compliance, maximal expiratory flow at 50% total lung capacity (Vmax50), and forced expiratory flow at 0.1 s (FEV 0.1) at low (200 micrograms kg-1) or at high doses (2 mg kg-1), except that it produced a slight bronchial constricting action (decreases in both Vmax 50 and FEV 0.1) at high doses (2 mg kg-1) via intratracheal instillation. 3. Beginning 15 min after exsanguination, there was a marked temporal decrease in FEV 0.1, indicating a gradual increase in airway constriction with time. 4. Administration of either fullerenol-1 or deferoxamine, or pre-exposure to chronic hypoxia significantly ameliorated the exsanguination-induced bronchoconstriction. The results provide evidence that oxygen radicals play an important role in exsanguination-induced airway constriction. 5. The significant effects of the increased antioxidants and deferoxamine,however, cannot be explained by the alteration in either tracheal neutral endopeptidase activity or lung tissue substance P level.

Animals↗