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At least 19 recordsLinked to original sources
PubMed1976

Microbial iron chelates with iron donor properties in hemoglobin-synthesizing cells.

Iron incorporation into Friend virus infected leukemic murine spleen cells was studied using the two fungal iron trihydroxamates, fusigen and ferricrocin. Incorporation of 55Fe was measured by isolation of hemoglobin after dimethylsulfoxide-induced hemoglobin synthesis and compared with iron incorporation from 55Fe-labeled ferric citrate.

Animals↗
PubMed1975

Kinetic studies on the specificity of chelate-iron uptake in Aspergillus.

Three strains of the fungus Aspergillus, Aspergillus quadricinctus (E. Yuill), A. fumigatus (Fresenius), and A. melleus (Yukawa), each producing different iron-chelating compounds during iron-deficient cultivation, were used for 55Fe3+ uptake measurements. Iron from chelates of the ferrichrome-type family was taken up by young mycelia of all strains tested, irrespective of the ferrichrome-type compound these strains predominantly produce in low-iron cultures. Ferrichrysin-producing strains, however, seem to favor ferrichrysin iron uptake, whereas ferrichrome, ferricrocin, and even ferrirubin showed similar iron transport properties in all of these strains. Compared to iron uptake from ferrichrome-type compounds (Km approximately 4 uM) iron uptake from fusigen revealed completely different kinetic values (Km approximately 50 to 80 muM). Iron from exogenous chelates, e.g., from coprogen produced by Neurospora crassa for ferrioxamine B produced by Streptomyces pilosus, can obviously not be taken up by Aspergillus, confirming the pronounced specificity of chelate-iron transport in fungi.

Aspergillus↗
PubMed1978

Deferoxamine-chelatable iron in hemochromatosis and other disorders of iron overload.

Deferoxamine-chelatable iron was measured in 103 patients with known or suspected iron overload. All of 34 patients with untreated hemochromatosis had distinctly elevated values for deferoxamine-chelatable iron. The mean value in these cases was significantly greater than that in patients with cirrhosis, who had little or no stainable hepatic iron. In 15 patients with hemochromatosis who were tested sequentially during the course of phlebotomy therapy, deferoxamine-chelatable iron proved a reliable index of the degree of reduction of storage iron. In 22 additional patients with partially treated hemochromatosis and 14 with iron overload accompanying chronic anemia, this test correlated well with the magnitude of iron deposits in liver or bone marrow. In patients with unexplained elevations of serum iron, normal or only slightly elevated deferoxamine-chelatable iron correctly indicated that storage (hepatic) iron was not excessive. The test was more reliable than determination of serum iron or transferrin saturation as an indicator of increased storage iron. Elevated values could not be attributed to disturbed liver function. Determination of deferoxamine-chelatable iron is a safe, practical, and useful procedure for identifying persons with increased iron stores and for assessing the effect of phlebotomy therapy.

Adult↗
PubMed1978

Mechanism of iron chelation in the hypertransfused rat: definition of two alternative pathways of iron mobilization.

The mechanism of action of two recently identified iron-chelating drugs, RA and CHA, was compared with that of two well-known chelating agents, DF and DTPA, in hypertransfused rats labeled with selective parenchymal and RE cell radioiron probes. The existence of two alternative pathways for the in vivo chelation of iron has been indicated by the present findings. The first of these pathways involves the extracellular chelation of RE cell iron and its subsequent excretion in the urine. The second pathway is concerned with the intracellular binding of hepatic parenchymal cell iron and its subsequent excretion in the bile. Iron chelation by DTPA is restricted to the first pathway, whereas iron chelation by CHA is confined to the second pathway. DF and RA have a dual effect and are able to enhance the urinary excretion of RE cell iron as well as the biliary excretion of hepatic parenchymal iron. Hypertransfused rats are a simple and useful experimental model for the study of iron mobilization by chelating agents of potential clinical usefulness. However, further studies are required to show whether the pathways of iron chelation identified in rats may represent the mechanism of iron chelation in patients with transfusional iron overload.

Animals↗
PubMed1978

Iron chelation in thalassemia: mechanism of desferrioxamine action.

The mechanism of iron chelation was studied in 16 patients with homozygous beta-thalassemia. Following the i.v. infusion of desferrioxamine, chelated iron accumulated in the plasma and its maximal level at 2 h was closely correlated with the 24-h excretion of iron in the urine. The high specific activity of chelated urinary iron indicated that the chelatable pool was much smaller than the total storage iron pool and was probably derived from nonviable red blood cells in the reticuloendothelial system. This postulate was confirmed by the direct measurement of specific activities in the spleen and liver, revealing identical values of chelated urinary iron and of iron in reticuloendothelial tissues. These findings support the concept of an easily chelatable iron pool that is derived from the catabolism of hemoglobin.

Adolescent↗
PubMed1978

Intensive iron-chelation therapy with desferrioxamine in iron-loading anaemias.

1. Urinary iron excretion after desferrioxamine has been examined in nine patinets with different iron-loading anaemias. Particular attention has been paid to individual variation in response and the kinetics of iron removal in order to determine the most efficient and convenient method of administration. 2. Twelve-hour subcutaneous infusions of desferrioxamine were comparable with intravenous infusions and gave a mean value of 62% more iron excretion than similar intramuscular bolus doses (range 20--125%). 3. Increasing doses as 12 h subcutaneous infusions produced a linear increase in iron excretion, which was followed by a tendency to reach a plateau. Iron excretion varied greatly between patients, was not related solely to age or estimated iron load, and in most cases was increased by ascorbic acid saturation. 4. Maximum iron-excretion rates were achieved after 3--6 and then maintained throughout an infusion. With bolus injections excretion rates declined rapidly after the first 6 h, during which approximately 60% of the total iron excretion occurred. 5. The dose and method of administration should be 'tailor-made' for each patient. Overnight 12 h subcutaneous infusions can be both as effective as similar doses given over 24 h and a practical way of achieving substantial negative iron balance. 6. Since children receiving regular blood transfusions for congenital anaemias such as thalassaemia usually die at the end of the second decade, this approach to iron chelation offers the possibility of alleviating what have hitherto been fatal-iron loading states.

Adolescent↗
PubMed1976

The use of chang cells cultured in vitro to evaluate potential iron chelating drugs.

A number of iron chelating agents, consisting largely of hydroxamic acid and benzoic acid derivatives, have been studied in an in vitro Chang cell culture system to determine their effect on cellular iron uptake, ferritin synthesis and the incorporation of iron into ferritin. The results have been compared with those of a previous study in which iron balance was determined in hypertransfused rats. Both techniques appear to be of value in screening new iron chelating agents for potential therapeutic use in patients with iron overload.

Benzoates↗
PubMed1976

Iron-chelating compound from Mycobacterium avium.

A iron-chelating monohydroxamate was isolated from cultures of Mycobacterium avium grown on an iron-limiting medium. The hydroxyamate metabolite was characterized by chemical degradation and spectral measurements as L-alpha-asparaginyl-L-alpha-(N-hydroxy)-asparagine.

Asparagine↗
PubMed1978

Microbial iron-chelators and their action on Klebsiella infections in the skin of guinea-pigs.

Preparations of catechols from ethyl acetate extracts of cultures of Klebsiellae in a low-iron medium contained iron-chelators whose potency was measured by the reversal of the bacteristasis of Escherichia coli and klebsiellae in unheated horse serum, and of the growth-inhibition of these two organisms by ethylene diamine di-orthohydroxyphenyl acetic acid (EDDA). As revealed by in situ tests of paper chromatograms, there was a multiplicity of biologically active chelators in the preparations. Catechols from strains both of high and low virulence for guinea-pigs enhanced the skin infectivity of most of the 10 Klebsiella strains tested. The enhancement was roughly proportional to iron-enhanceability with the 6 iron-enhanceable (E+) strains, though not as great as that by iron. But of the 4 (Eo) strains not enhanceable by iron, two were moderately enhanced by the catechols. The Streptomyces iron-chelator desferrioxamine B also enhanced infectivity, again roughly in proportion to the iron enhanceability of the strains; though one Eo strain was substantially enhanced. The synthetic iron-chelator EDDA did not enhance infection.

Animals↗
PubMed1978

Iron chelation therapy with deferoxamine in Cooley anemia.

The iron-chelating agent, deferoxamine, was studied in 16 patients with thalassemia major. Urinary excretion of iron in response to 0.75 gm of deferoxamine, intramuscularly, ranged from 2.2 to 44.8 mg Fe/24 hours. In response to a subcutaneous infusion of 1.5 gm deferoxamine for 18 hours, iron excretion increased by an average of 240%. The intravenous infusion of large doses of deferoxamine for 18 hours resulted in the highest rate of iron excretion, as much as 447.5 mg Fe/24 hours in response to 16 gm of deferoxamine. Administration of vitamin C increased chelation-induced excretion of iron in most patients more than five years of age. Preliminary evidence suggests that further iron accumulation can be prevented and excessive iron stores can be depleted by the intramuscular, subcutaneous, or intravenous administration of deferoxamine.

Adolescent↗
PubMed1979

Rhodotorulic acid--investigation of its potential as an iron-chelating drug.

The use of rhodotorulic acid (RA) as an iron-chelating drug was suggested by experiments in hypertransfused rats in which urinary and fecal iron excretion were significantly enhanced in response to RA. The toxicity of the drug appears to be minimal at a parenteral dose less than 250 mg/kg. An increased excretion of zinc was the only notable side effect of the drug at the doses used. When administered i.v. to humans, RA was only 16% more effective than desferrioxamine (DF). Pharmacokinetic studies showed that RA persisted in the bloodstream of dogs 6 times longer than desferrioxamine after an intravenous injection. Accordingly RA was evaluated as a potential repository drug. While animal experiments were encouraging, human subjects experienced a painful local reaction to RA administered either i.m. or s.c. as a suspension in physiological saline. Accordingly it appears that RA is best looked at as a second line drug, unless a means can be found to obviate local inflammatory reactions.

Adult↗
PubMed1978

The development of new iron-chelating drugs. II.

For the past several years, we have searched for an orally effective iron-chelating drug and report here on several compounds which warrant further investigations based on their ability to promote iron excretion in the hypertransfused rat. Administrered orally, 2,3-dihydroxybenzyolglycine induced both urinary and fecal iron excretion, suggesting that a conjugate of 2,3-dihydroxybenzoic acid may be more efficacious than the parent compound. Tropolone, although rather toxic, stimulated fecal excretion of iron when given p.o. at low doses. Evaluation of less toxic derivatives of tropolone appears to be justifiable. L-Histidine may also be of use in chelatin therapy. Fecal iron excretion is significantly increased in response to oral doses of this essential amino acid. Lastly, cholylhydroxamic acid proved to be the most efficacious oral agent examined thus far. A marked increase in fecal iron excretion results from its administration.

Animals↗
PubMed1975

Enterobacterial chelators of iron: their occurrence, detection, and relation to pathogenicity.

In or on agar media, low-density seedings of enterobacteria fail to grow in the presence of certain concentrations of ethylene diamine-di-orthohydroxyphenyl acetic acid (EDDA); on the other hand, high-density seedings not only grow but secrete iron chelators which release the iron bound by the EDDA in the medium and stimulate the growth of low-density seedings. Plates of media containing EDDA with low-density seedings of indicator organisms were used to survey iron-chelator production in seven enterobacterial genera, including a number of virulent smooth (S) forms from which rough (R) mutants had been obtained. An examination of over 80 strains of Aeromonas, Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella and Shigella species indicated that the iron chelators from bacteria in all these genera were functionally interchangeable. Chelator production was equally good with randomly selected avirulent and virulent strains of Klebsiella spp. and E. coli; and with the S forms and their avirulent R mutants in one pair of escherichiae, six pairs of salmonellae (4 species) and six pairs of shigellae (3 species). As determinable in vitro, the capacity to synthesise iron chelators is clearly no index of the capacity of a strain to proliferate in vivo.

Aeromonas↗