SEARCH · Search PubMed
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.
Among the ferric compounds studied, cytochrome C, methemoglobin, lactoperoxidase, ferritin and ferric ion, in addition to catalase, had the ability to oxidize metallic mercury in the presence of hydrogen peroxide. On the other hand, hematin, the active center of catalase, did not oxidize metallic mercury. The results are consistent with the increased oxidation and uptake of mercury in the liver by acatalasemia mice.
Several prior studies suggest that ferric compounds bind dietary phosphate and possess clinical potential as phosphate binding agents. Therefore, this study was conducted to measure the effect of several ferric compounds on intestinal phosphate binding and absorption. Balance studies lasting 2 to 4 wk were performed in normal and azotemic (achieved by subtotal nephrectomy) rats maintained on a 1.02% phosphorus diet supplemented with ferric salts (formulated to 0.95% Fe) or no ferric salt (control). In rats with normal renal function (average creatinine clearance, 4.0 ml/min per kg), the average net intestinal absorption of phosphate over all balance periods was 103.3 mg/d for the control group versus 84.7 mg/d for the ferric citrate group (P < 0.005). In the azotemic rats (average creatinine clearance, 3.3 ml/min per kg), the average net intestinal absorption of phosphate over all balance periods was significantly lower for the three ferric groups than the control groups (P < or = 0.02): 95.3 mg/d for the control group versus 75.6 mg/d for the ferric ammonium citrate-treated group (P = 0.058), 77.0 mg/d for the ferric citrate-treated group (P = 0.057), and 62.5 mg/d for the ferric chloride-treated group (P < 0.002). Urinary phosphate excretion fell, sometimes to an even greater extent than did intestinal absorption, yielding no net reduction in phosphate balance in these growing, young animals with relatively preserved renal function. Calcium balance was largely unaffected by the ferric compounds. There were trends toward decreased serum phosphorus and parathyroid hormone concentrations and increased iron and hematocrit in the ferric-treated azotemic groups. All tested ferric compounds were well tolerated, but animal growth was stunted in the ferric chloride animals compared with the control group. Phosphate binding was estimated at 85 to 180 mg per gram of elemental iron, which is comparable to other phosphate binding agents. Ferric salts decrease net intestinal phosphate absorption and hold promise for the treatment of phosphate retention in patients with renal failure.
Lipid peroxidation effects of ferric maltol have been compared with those of ferrous sulphate both in lecithin liposomes and in brush border and mitochondrial membranes prepared from rat small intestine. Ferrous sulphate, but not ferric maltol, initiated peroxidation in liposomes as measured by conjugated diene production, but, with 500 microM ascorbic acid present, both caused intense peroxidation which was inhibitable by N2, tocopherol, maltol and ferrous chelators, but not by OH or H2O2 scavengers. The rate of peroxidation increased with ferrous sulphate concentration up to 100 microM but was independent of ferric maltol concentration between 5-500 microM. Material eluted from rat small intestine contained a reducing factor, similar in size to ascorbic acid, capable of generating ferrous ions from ferric maltol and initiating peroxidation. Peroxidation in mitochondrial membranes appeared unaffected by addition of iron whilst that in brush border membranes was detectable only in the presence of iron. At iron concentrations of 100 microM and above ferric maltol produced less liposomal peroxidation than ferrous sulphate. Maltol itself may delay recycling of Fe3+ to Fe2+. Thus ferric maltol could provide a less toxic alternative to ferrous salts in the oral treatment of iron-deficiency.
All available results from critical hemoglobin regeneration tests, postabsorption serum iron concentration studies, 59Fe erythrocyte incorporation and 59Fe whole-body retention measurements demonstrate that humans do absorb ferrous iron between 4 and 10 times (in the average about 5 times) better than ferric iron from therapeutic oral 50--250 mg iron doses. Ferrous sulfate iron is 3 to 4 times better available than the iron from ferric ammonium citrate or sulfate. Whereas 100 mg of ferrous sulfate iron/day are sufficient for an optimal oral compensation iron therapy and to produce initial hemoglobin regeneration rates of about 0.26 g/100 ml/day, 400 to 1000 mg of ferric iron/day are necessary for the same therapeutic effect because of the poor bioavailability of ferric iron. The ratio of the dose-absorption relationships for ferric and ferrous 59Fe was shown to decrease from 0.43 for a diagnostic 0.56 mg Fe dose to 0.21 for the therapeutic 50 mg Fe dose in subjects with normal iron stores. Absorption ratios of 0.65 for the 0.56 mg Fe dose and 0.26 for the 50 mg Fe dose were measured in subjects with depleted iron stores. At all dose levels the superior bioavailability of ferrous iron was demonstrable. A high-molecular weight ferric hydroxide-carbohydrate complex (MW similar to 30 000) was palatable but so poorly absorbed that is was practically without effect on hemoglobin regeneration even at a daily 300 mg Fe dose. Following several warnings such a useless commerecial oral iron preparation was finally withdrawn from the market. The iron from any high-molecular weight carbohydrate complex of ferric hydroxide has to be suspected to be poorly absorbed and therefore therapeutical useless, unless the opposite has been demonstrated with a reliable bioassay (59Fe absorption whole-body retention and hemoglobin regeneration test). A low-molecular weight so-called ferric hydroxide-fructose complex was shown to contain iron of more or less the same poor bioavailability as contained in ferric chloride since the iron from ferrous sulfate was about 5 times better absorable. The good absorption of ferrous sulfate iron was not further augmented by even very large oral doses of fructose since this carbohydrate did not improve the ferrous iron absorption at a fructose: Fe molar ratio of 106:1. Trivalent iron in simple compounds like ferric ammonium citrate or in low- and high-molecular weight carbohydrate complexes of ferric hydroxide is so poorly available for intestinal iron absorption in man that it cannot be used for a fast and reliable oral iron therapy with reasonably low doses as it can be easily practised with quick-lease preparations of ferrous sulfate at a 100 mg Fe2
The effect of ferric compounds in therapy of iron deficiency anemia is doubtful; however, the absorption of iron is not affected negatively by food or drugs. In our Well Baby Clinic, ferric polymaltose (6 mg/kg/d) was given to 59 infants (Group 1) and ferrous sulphate (same doses) was given to 64 infants (Group 2) (74 +/- 9 d, 70 +/- 7 d, respectively). These infants had iron deficiency anemia, and their therapy was continuous. Ferric polymaltose was not as effective as ferrous sulphate, although it increased hemoglobin and serum iron. Mean corpuscular volume and serum ferritin were not significantly changed after therapy. For this reason, we prefer to use only ferrous salts in therapy.
The mammalian host specifically limits iron during Histoplasma capsulatum infection, and fungal acquisition of iron is essential for productive infection. H. capsulatum expresses several iron acquisition mechanisms under iron-limited conditions in vitro. These components include hydroxamate siderophores, extracellular glutathione-dependent ferric reductase enzyme, extracellular nonproteinaceous ferric reductant(s), and cell surface ferric reducing agent(s). We examined the relationship between these mechanisms and a potential role for the extracellular ferric reductase in utilization of environmental and host ferric compounds through the production of free, soluble Fe(II). Siderophores and ferric reducing agents were coproduced under conditions of iron limitation. The H. capsulatum siderophore dimerum acid and the structurally similar basidiomycete siderophore rhodotorulic acid acted as substrates for the ferric reductase, and rhodotorulic acid removed Fe(III) bound by transferrin. The mammalian Fe(III)-binding compounds hemin and transferrin served both as substrates for the ferric reductase and as iron sources for yeast-phase growth at neutral pH. In the case of transferrin, there was a correlation between the level of iron saturation and efficacy for both of these functions. Our data are not consistent with an entirely pH-dependent mechanism of iron acquisition from transferrin, as has been suggested to occur in the macrophage phagolysosome. The foreign siderophore ferrioxamine B also acted as a substrate for the ferric reductase, while the foreign siderophore ferrichrome did not. Both ferrioxamine and ferrichrome served as iron sources for yeast- and mold-phase growth, the latter presumably by some other acquisition mechanism(s).
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Ferric maltol is a novel ferric iron compound with potential use as an oral therapy for iron deficiency anaemia. Using a single, low dose iron absorption test we compared absorption of ferric maltol with absorption of ferrous sulphate in 21 iron deficient subjects. Absorption of 10 mg of ferric maltol as either aqueous solution or a single tablet compared favourably with that of an equivalent dose of ferrous sulphate. At a higher, more therapeutic dose of 60 mg elemental iron as tablets, absorption of ferric maltol appeared to be both more rapid and total absorption greater, than that seen with ferrous sulphate. We conclude that iron from ferric maltol, both at low dose and higher, more therapeutic doses, is at least as well absorbed as from ferrous sulphate. Ferric maltol is the first ferric iron formulation to be absorbed to a degree equivalent to that of ferrous iron salts and may represent a viable form of administration for ferric iron in the treatment of iron deficiency anaemia.
Explore the source record for details and available documents.
Bacterial biofilms are thought to aid in the survivability of a variety of intractable infections in humans. Specifically, biofilm production in Pseudomonas aeruginosa has been shown to play a significant role in chronic infection of cystic fibrosis (CF) patients. Unfortunately, no clinically effective inhibitors of biofilm formation are available. A rapid screen of 4509 compounds for nonantibiotic biofilm inhibitors in Pseudomonas aeruginosa PA14 was executed in 384-well plates. Among those compounds, ferric ammonium citrate inhibited biofilm formation in a dose-dependent manner; other iron salts functioned similarly. In addition to biofilm inhibition in static culture, pregrown biofilms could be disrupted and cleared by switching to iron-rich media in flow-chamber experiments. Furthermore, P. aeruginosa strains taken from the sputum of 20 CF patients showed a similar response to elevated iron levels. Previous expression-profiling analyses demonstrated that high levels of iron repress the expression of genes whose products are essential for scavenging iron and that expression of these genes is critical for virulence. Our results, combined with existing transcriptional-profiling data, now indicate that elevated iron concentrations repress the expression of certain genes essential for biofilm production in P. aeruginosa.
The behaviour of sideremia has been studied in order to assess the intestinal absorption of iron of a new compound, ferric chondroitin sulfate after oral administration in 12 normal volunteers. After administration of 90 mg of iron as ferric chondroitin sulfate, sideremia rose from a basal value of 88 +/- 27 micrograms/dl to a value of 128 +/- 22 micrograms/dl at the third hour. Variance analysis showed that the increases were statistically significant (F = 27.7; p less than 0.00001). In the same subjects, the test was carried out in accordance with a randomised crossover design in two periods after administration of 91 mg of ferritin iron: sideremia rose from a basal value of 92 +/- 27 micrograms/dl to a value at the third hour of 97 +/- 28 micrograms/dl, moderate increases but statistically significant (F = 3.2; P = 0.0354). Variance analysis by repeated measurements showed that increases in sideremia were significantly higher after iron administration as ferric chondroitin sulfate than after administration of ferritin iron (F = 13.18; p = 0.0042). This study documents the good bioavailability of the iron contained in ferric chondroitin sulfate.
The mutagenicity of the potent carcinogen benzo(a)pyrene proved to be lost by binding with hemin and other tested compounds. The association constant (Kass) and the desmutation constant (Kmut) of benzo(a)pyrene and hemin were 8.5 x 10(4) M(-1) and 7.0 x 10(-4) M(-1), respectively. The correlation coefficient (gamma) of the association and the desmutation of benzo(a)pyrene and hemin was nearly 1, and the coefficient of regression of association on the desmutation, gamma (sigma ass/sigma mut), was 0.78. The correlation of other compounds, ferric chloride among transient metals, and 3,3'-diaminodipropylamine and p-phenylenediamine, were also almost 1 in both values, but their Kass an Kmut were must smaller than those of hemin: Kass:Kmut, 525 M(-1):520 M(-1) for ferric chloride, 2.2 x 10(3) M(-1):2.3 x 10(3) M(-1) for diaminodipropylamine and 175 M(-1):125 M(-1) for p-phenylenediamine. Good agreement of Kass and Kmut means that the desmutation of benzo(a)pyrene is caused by binding with tested materials.
We investigated the effect of Fe deficiency on the nutritive utilization of Fe, Ca, P and Mg in rats. Aside from the well known depletion of Fe in liver, femur and sternum with low values of Hb, Fe deficiency impaired Ca, P and Mg metabolism at different degrees. Iron deficiency altered Mg absorption, lowered the concentration of Ca in the liver, femur and sternum, raised the concentration of P and Mg in the liver, and decreased P in the femur. The altered status was not completely rectified by iron supplementation as the animals were still slightly anemic at the end of the study. The second purpose of the study was to evaluate the ability of three iron compounds (ferric citrate, ferrous sulfate and ferrous ascorbate) to correct the undesirable effects of Fe deficiency. Ten days after treatment with these diets, Fe-deficient rats still had reduced Mg absorption, especially those fed ferric citrate. The concentrations of hemoglobin approached normal values in all groups; however, serum Fe remained low, indicating that Fe reserves were still depleted. Hepatic and femoral Fe concentrations were also lower in all Fe-deficient groups regardless of the diet given, compared with their respective controls, whereas Fe concentrations in the sternum increased significantly with all three diets, suggesting an increase in erythropoiesis. The concentration of Ca, P and Mg in liver approached normal values, and appeared to normalize in the femur, except that Ca and P concentrations remained low with the citrate diet. In the sternum, a site assumed to have higher requirements for these minerals, the concentrations of Ca, P and Mg also increased. These findings indicate that Fe is involved in the bone mineralization, and that in physiological terms, Fe interacts favorably with Ca, P and Mg metabolism, since Fe deficiency altered the status of these metals. These findings also suggest that ferrous ascorbate and ferrous sulfate were more effectively absorbed than was ferric citrate.
Explore the source record for details and available documents.