PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Ferrous Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 37 records · Page 2Linked to original sources
PubMed2003

Pathophysiology of the optic neuropathy associated with Friedreich ataxia.

OBJECTIVES: To describe the optic neuropathy associated with the genetic defect in Friedreich ataxia and suggest a pathophysiologic mechanism. METHODS: An experimental model of retinal ganglion cell death in the presence of metal chelation was used to test a hypothetical mechanism for the optic neuropathy of Friedreich ataxia. RESULTS: Study of cultured rat retinal ganglion cells suggests that abnormal regulation of intracellular iron levels could increase sensitivity to reactive oxygen species and lead to cell death in these metabolically active tissues. CONCLUSION: We hypothesize that decreased expression of frataxin, the mutated gene in Friedreich ataxia, could cause an optic neuropathy by increasing the sensitivity of retinal ganglion cells to oxidative stress.

Animals↗
PubMed1994

Ferric iron potentiates cell depolarization by a circulating shock protein.

OBJECTIVE: To determine whether or nor iron affects the depolarizing activity of a circulating shock protein that appears in plasma after hemorrhage. DESIGN: Randomized design. SETTING: University laboratory. ANIMALS: Healthy male Sprague-Dawley rats weighing 300 to 400 g with femoral artery and vein cannulas placed 4 days before hemorrhage. INTERVENTION: A 20-mL/kg hemorrhage and plasma collection. MAIN OUTCOME MEASURES: Depolarizing activity was measured as the increased fluorescence of an oxonol dye in the presence of Fe3+, Fe2+, or the iron chelator deferoxamine mesylate and was titrated against increasing concentrations of circulating shock protein or iron. Circulating shock protein was derived from plasma and was purified in two steps: stepwise ammonium sulfate precipitation followed by denaturing ion-exchange chromatography and refolding. RESULTS: At physiologic concentrations, Fe3+ but not Fe2+ potentiated the depolarizing activity of plasma after ammonium sulfate. Addition of deferoxamine abolished activity. Denaturing chromatography removed nearly all the depolarizing activity; however, Fe3+ restored activity to this fraction. Fe3+ increased total activity and decreased the concentration at which 50% activity was observed. CONCLUSION: These data indicate that physiologic concentrations of Fe3+ may act to modulate the depolarizing activity of circulating shock protein that in turn mediates the intracellular accumulation of salt and water in shock.

Animals↗
PubMedDate not supplied

An intracellular transit iron pool.

It seems likely that iron which has crossed the cell membrane and has been released from transferrin enters a labile intermediate pool from which it is available for haem synthesis, for the activation of iron-dependent enzymes, for incorporation into ferritin or for a return to extracellular transferrin. Enlargement of this pool stimulates ferritin synthesis. Iron probably enters the transit pool not only from transferrin but also as a result of endogenous haem breakdown and the mobilization of ferritin iron. Evidence for the occurrence of the transit pool has been obtained for reticuloendothelial cells, red cells precursors, cultured Chang cells and liver. It is suggested that the transit pool consists of a low molecular weight complex and that this is a major source of the iron chelated by agents such as desferrioxamine. No more precise characterization has been possible up to the present time.

Animals↗
PubMed2002

Effects of citrinin on iron-redox cycle.

The ability of the mycotoxin citrinin to act as an inhibitor of iron-induced lipoperoxidation of biological membranes prompted us to determine whether it could act as an iron chelating agent, interfering with iron redox reactions or acting as a free radical scavenger. The addition of Fe3+ to citrinin rapidly produced a chromogen, indicating the formation of citrinin-Fe3+ complexes. An EPR study confirms that citrinin acts as a ligand of Fe3+, the complexation depending on the [Fe3+]:[citrinin] ratios. Effects of citrinin on the iron redox cycle were evaluated by oxygen consumption or the o-phenanthroline test. No effect on EDTA-Fe2+-->EDTA-Fe3+ oxidation was observed in the presence of citrinin, but the mycotoxin inhibited, in a dose-dependent manner, the oxidation of Fe2+ to Fe3+ by hydrogen peroxide. Reducing agents such as ascorbic acid and DTT reduced the Fe3+-citrinin complex, but DTT did not cause reduction of Fe3+-EDTA, indicating that the redox potentials of Fe3+-citrinin and Fe3+-EDTA are not the same. The Fe2+ formed from the reduction of Fe3+-citrinin by reducing agents was not rapidly reoxidized to Fe3+ by atmospheric oxygen. Citrinin has no radical scavenger ability as demonstrated by the absence of DPPH reduction. However, a reaction between citrinin and hydrogen peroxide was observed by UV spectrum changes of citrinin after incubation with hydrogen peroxide. It was also observed that citrinin did not induce direct or reductive mobilization of iron from ferritin. These results indicate that the protective effect on iron-induced lipid peroxidation by citrinin occurs due to the formation of a redox inactive Fe3+-citrinin complex, as well as from the reaction of citrinin and hydrogen peroxide.

Ascorbic Acid↗
PubMed2003

Comparison of the chemical properties of iron and cobalt porphyrins and corrins.

Density functional calculations have been used to compare various geometric, electronic and functional properties of iron and cobalt porphyrin (Por) and corrin (Cor) species. The investigation is focussed on octahedral M(II/III) complexes (where M is the metal) with two axial imidazole ligands (as a model of b and c type cytochromes) or with one imidazole and one methyl ligand (as a model of methylcobalamin). However, we have also studied some five-coordinate M(II) complexes with an imidazole ligand and four-coordinate M(I/II) complexes without any axial ligands as models of other intermediates in the reaction cycle of coenzyme B12. The central cavity of the corrin ring is smaller than that of porphine. We show that the cavity of corrin is close to ideal for low-spin Co(III), Co(II), and Co(I) with the axial ligands encountered in biology, whereas the cavity in porphine is better suited for intermediate-spin states. Therefore, the low-spin state of Co is strongly favoured in complexes with corrins, whereas there is a small energy difference between the various spin states in iron porphyrin species. There are no clear differences for the reduction potentials of the octahedral complexes, but [Co(I)Cor] is more easily formed (by at least 40 kJ mole(-1)) than [Fe(I)Por]. Cobalt and corrin form a strong Cobond;C bond that is more stable against hydrolysis than iron and porphine. Finally, Fe(II/III) gives a much lower reorganisation energy than Co(II/III); this is owing to the occupied d(z2) orbital in Co(II). Altogether, these results give some clues about how nature has chosen the tetrapyrrole rings and their central metal ion.

Cobalt↗
PubMed2006

The coordination chemistry of FeCl3 and FeCl2 to bis[2-(2,3-dihydroxyphenyl)-6-pyridylmethyl](2-pyridylmethyl)amine: access to a diiron(III) compound with an unusual pentagonal-bipyramidal/square-pyramidal environment.

Coordination of FeCl3 to the title ligand yields a mononuclear iron(III) complex 1, which was characterized by spectroscopic techniques and X-ray diffraction. The ligand is (kappa3-N) tridentate and the metal, which lies in a pseudo-octahedral environment, is bound to a phenolate group from the catechol substituent. The dichloroiron(II) complex 2 was easily obtained by metalation of the ligand with FeCl2 and characterized by various spectroscopic techniques. In their cyclic voltammograms both 1 and 2 display the same reversible FeII/FeIII wave at E1/2=10 mV (vs. SCE). Reduction of compound 1 with Zn/Hg yields 2', which displays identical properties to 2. Taken together, these findings indicate that in spite of the different oxidation state of the metal in 2, no major geometrical/structural change is observed at the metal center with respect to 1. The reaction of 2 with dioxygen in the absence of organic substrates proceeds extremely rapidly and yields compound 3, which is a diiron(III) derivative whose X-ray crystal structure is also reported. The possibility of a radical-based mechanism is discussed. Compound 3 displays an unusual geometry: one iron(III) center is seven-coordinate, whereas the other lies in a square-pyramidal environment. The two iron atoms are bridged by the catecholato substituents. To the best of our knowledge, 3 is the first example of a seven-coordinate iron(III) derivative with tris(2-pyridylmethyl)amine ligands.

Chlorides↗
PubMed2004

Structural and magnetic investigations of the mixed-valence Fe(II,III) two-dimensional layer complex, [Fe2(II) Fe2(III)(HCOO)10(C6H7N)6]n.

The structure of the complex, [Fe2(II)Fe2(III)(HCOO)10(C6H7N6)n, (1) exhibits a neutral two-dimensional layer network of alternating iron(II) and iron(III) ions, bridged equatorially by formate groups. All iron atoms are octahedrally coordinated, with iron(III) coordinating axially to one gamma-picoline and one formate group, while the iron(II) centers interact axially with two gamma-picoline groups, above and below the layer plane. The complex crystallizes in the triclinic space group P1 at all studied temperatures [at 120 K, the cell dimensions are: a = 10.228(1), b = 12.071(1), c = 12.072(1) A, alpha = 89.801(2), beta = 71.149(2), gamma = 73.371(2) degrees]. An intralayer antiferromagnetic exchange interaction of J = -2.8 cm(-1) between iron(II) and iron(III) was observed in the magnetic studies. Decreasing the temperature to close to 20 K causes a magnetic-ordering phenomenon to occur and a low-temperature phase with a long-range antiferromagnetic spin orientation appears. The magnetic phase transition was confirmed by Mössbauer spectroscopic studies at temperatures above and below the critical temperature. Structural information of 1 from synchrotron X-ray diffraction data collected at room temperature and 16 K suggests that the antiferromagnetic ordering is caused by an enhanced pi-pi interaction between chi-picoline groups from adjacent layers.

Crystallography, X-Ray↗
PubMed2001

Comparison of iron-catalyzed DNA and lipid oxidation.

Lipid and DNA oxidation catalyzed by iron(II) were compared in HEPES and phosphate buffers. Lipid peroxidation was examined in a sensitive liposome system constructed with a fluorescent probe that allowed us to examine the effects of both low and high iron concentrations. With liposomes made from synthetic 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine or from rat liver microsomal lipid, lipid peroxidation increased with iron concentration up to the range of 10--20 microM iron(II), but then rates decreased with further increases in iron concentration. This may be due to the limited amount of lipid peroxides available in liposomes for oxidation of iron(II) to generate equimolar iron(III), which is thought to be important for the initation of lipid peroxidation. Addition of hydrogen peroxide to incubations with 1--10 microM iron(II) decreased rates of lipid peroxidation, whereas addition of hydrogen peroxide to incubations with higher iron concentrations increased rates of lipid peroxidation. Thus, in this liposome system, sufficient peroxide from either within the lipid or from exogenous sources must be present to generate equimolar iron(II) and iron(III). With iron-catalyzed DNA oxidation, hydrogen peroxide always stimulated product formation. Phosphate buffer, which chelates iron but still allows for generation of hydroxyl radicals, inhibited lipid peroxidation but not DNA oxidation. HEPES buffer, which scavenges hydroxyl radicals, inhibited DNA oxidation, whereas lipid peroxidation was unaffected since presumably iron(II) and iron(III) were still available for reaction with liposomes in HEPES buffer.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1991

Inhibition of human hepatocellular carcinoma and hepatoblastoma cell lines by deferoxamine.

Inhibition of human hepatocellular carcinoma (PLC/PRF/5 and Hep3B) or hepatoblastoma (Hep G2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (DFX) in the culture medium was evaluated. When PLC/PRF/5 cells were maintained for 7 days in 30 or 60 microM DFX, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (AFP) was produced, and supernatant endpoint dilution titers of hepatitis B surface antigen (HBsAg) were reduced 1-2 logs. PLC/PRF/5 cells maintained for 7 days without DFX (simultaneous controls) grew to confluence, produced AFP that reached 10-60 ng/ml in the supernate, and the HBsAg titer remained constant or increased 1 log. Similar effects were observed in Hep3B and Hep G2 cells maintained in DFX (except that Hep G2 cells do not produce HBsAg), compared to simultaneous control cells grown in the absence of DFX. The growth of a human embryonic lung fibroblast cell line (Wl 38) was not significantly inhibited by DFX, although it grew at a slower rate than simultaneous control cells grown without DFX. Subsequent growth in FeSO4 of PLC/PRF/5, Hep3B, and Hep G2 cells that previously had been maintained in DFX did not reverse the effects of DFX. PLC/PRF/5 cells were also inhibited when maintained in medium containing equimolar concentrations of DFX and FeCl3 and in medium containing equimolar concentrations of DFX and FeSO4. PLC/PRF/5 cells were not inhibited by maintenance in up to 60 microM of another chelating agent that has a similar affinity for iron, calcium disodium versenate (EDTA). These studies show that DFX inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines regardless of the presence (PLC/PRF/5, Hep3B) or absence (Hep G2) of integrated hepatitis B virus DNA. The findings also suggest that the inhibition may have been due to mechanisms other than iron chelation.

Carcinoma, Hepatocellular↗
PubMed1990

Structural changes in astrocytes induced by seizures in a mode of temporal lobe epilepsy.

Injection of iron-chloride solution unilaterally into the hippocampus of albino rats induced transient seizure activity which lasted approximately 2 weeks. Frontal and parietal cortices of experimental rats, control rats which received NaCl injections, and unoperated normal rats were compared by means of a Golgi stain which demonstrated astrocytes and their processes in their entirety. Morphometric analysis showed that cortical astrocytes of rats having intermittent seizure activity over a prolonged period were significantly larger than cortical astrocytes of control rats. These findings indicate that seizure activity causes structural brain changes at anatomical sites distant from the hippocampal seizure focus. Similar phenomena may contribute to the development of psychiatric and neurological changes in the epileptic patient.

Animals↗
PubMed1993

Amide proton exchange rates of oxidized and reduced Saccharomyces cerevisiae iso-1-cytochrome c.

Proton NMR spectroscopy was used to determine the rate constant, kobs, for exchange of labile protons in both oxidized (Fe(III)) and reduced (Fe(II)) iso-1-cytochrome c. We find that slowly exchanging backbone amide protons tend to lack solvent-accessible surface area, possess backbone hydrogen bonds, and are present in regions of regular secondary structure as well as in omega-loops. Furthermore, there is no correlation between kobs and the distance from a backbone amide nitrogen to the nearest solvent-accessible atom. These observations are consistent with the local unfolding model. Comparisons of the free energy change for denaturation, delta Gd, at 298 K to the free energy change for local unfolding, delta Gop, at 298 K for the oxidized protein suggest that certain conformations possessing higher free energy than the denatured state are detected at equilibrium. Reduction of the protein results in a general increase in delta Gop. Comparisons of delta Gd to delta Gop for the reduced protein show that the most open states of the reduced protein possess more structure than its chemically denatured form. This persistent structure in high-energy conformations of the reduced form appears to involve the axially coordinated heme.

Amides↗
PubMed1998

Tetramer-dimer equilibrium of oxyhemoglobin mutants determined from auto-oxidation rates.

One of the main difficulties with blood substitutes based on hemoglobin (Hb) solutions is the auto-oxidation of the hemes, a problem aggravated by the dimerization of Hb tetramers. We have employed a method to study the oxyHb tetramer-dimer equilibrium based on the rate of auto-oxidation as a function of protein concentration. The 16-fold difference in dimer and tetramer auto-oxidation rates (in 20 mM phosphate buffer at pH 7.0, 37 degrees C) was exploited to determine the fraction dimer. The results show a transition of the auto-oxidation rate from low to high protein concentrations, allowing the determination of the tetramer-dimer dissociation coefficient K4,2 = [Dimer] 2/[Tetramer]. A 14-fold increase in K4,2 was observed for addition of 10 mM of the allosteric effector inositol hexaphosphate (IHP). Recombinant hemoglobins (rHb) were genetically engineered to obtain Hb with a lower oxygen affinity than native Hb (Hb A). The rHb alpha2beta2 [(C7) F41Y/(G4) N102Y] shows a fivefold increase in K4,2 at pH 7.0, 37 degrees C. An atmosphere of pure oxygen is necessary in this case to insure fully oxygenated Hb. When this condition is satisfied, this method provides an efficient technique to characterize both the tetramer-dimer equilibrium and the auto-oxidation rates of various oxyHb. For low oxygen affinity Hb equilibrated under air, the presence of deoxy subunits accelerates the auto-oxidation. Although a full analysis is complicated, the auto-oxidation studies for air equilibrated samples are more relevant to the development of a blood substitute based on Hb solutions. The double mutants, rHb alpha2beta2 [(C7) F41Y/(G4) N102A] and rHb alpha2beta2 [(C7) F41Y/(E10) K66T], show a lower oxygen affinity and a higher rate of oxidation than Hb A. Simulations of the auto-oxidation rate versus Hb concentration indicate that very high protein concentrations are required to observe the tetramer auto-oxidation rate. Because the dimers oxidize much more rapidly, even a small fraction dimer will influence the observed oxidation rate.

Adult↗
PubMed1993

Xanthine oxidase- and iron-dependent lipid peroxidation.

Xanthine oxidase and iron-dependent lipid peroxidation has been studied extensively in many model systems, yet several details of this process remain unclear. Because redox reactions of iron are important parameters of iron-catalyzed lipid peroxidation, we have examined the roles of superoxide and hydrogen peroxide, produced by xanthine oxidase, to oxidize and reduce iron and thereby affect iron-catalyzed lipid peroxidation. Thus, we compared lipid peroxidation catalyzed by xanthine oxidase and ADP:Fe(III) to that catalyzed by xanthine oxidase and ADP:Fe(II). An examination of the action of superoxide on iron oxidation and reduction revealed that superoxide is a better oxidant of ADP:Fe(II) than a reductant of ADP:Fe(III). A superoxide generating system (composed of xanthine oxidase and catalase) and ADP:Fe(II) also resulted in a greater amount of lipid peroxidation than superoxide and ADP:Fe(III). Hydrogen peroxide, as expected, only served as an Fe(II) oxidant. A comparison of the oxidant activities of either superoxide or hydrogen peroxide on ADP:Fe(II) and the corresponding effects on lipid peroxidation revealed that both oxidants were roughly equivalent. We conclude that superoxide and hydrogen peroxide, produced from xanthine oxidase, support iron-catalyzed lipid peroxidation through their participation in redox reactions of iron, that is, they facilitate Fe(II) oxidation or Fe(III) reduction necessary for lipid peroxidation. The relevance of the reactions of O2-. and H2O2 on physiological chelates of iron are discussed.

Adenosine Diphosphate↗
PubMed1993

The effect of changes in iron redox state on the activity of enzymes sensitive to modification of SH groups.

Iron ions in micromolar concentrations induced a rapid and selective inhibition of the activity of skeletal muscle creatine kinase (CK), sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and pyruvate kinase (PK). This effect of iron was dependent on the presence of adenine nucleotides and on the redox state of iron. Changing the redox state of the media created different Fe2+/Fe3+ ratios which selectively depressed different enzymes: depression of PK activity occurred when iron was predominantly in its reduced form and, consequently, when there was a high Fe2+/Fe3+ ratio; depression of SR Ca2+ uptake and SR Ca(2+)-ATPase activity occurred when the Fe2+/Fe3+ ratio was close to 1; depression of CK activity occurred when iron was predominantly in its oxidized form and the Fe2+/Fe3+ ratio was low. All iron-sensitive enzymes possessed sulfhydryl groups, accessible to N-ethylmaleimide (NEM), which were essential for their activity. The rate of inhibition of enzyme activity with NEM increased in the order PK < Ca(2+)-ATPase < CK. Iron-induced depression of CK and PK activities was reversible by dithiotreithol. Results suggest that changes in the redox state of cellular microenvironments, which inevitably occur during reperfusion of ischemic tissue or rapid increase in tissue oxygen consumption, may selectively depress the activity of several enzymes bearing SH groups that are sensitive to modifications and that are essential for their activity. Iron-induced depression of enzyme activity depends on the availability of iron bound to adenine nucleotides and possibly to other low molecular weight chelators and on the Fe2+/Fe3+ ratio generated by the induced redox change.

Animals↗