Altered transition metal homeostasis in mice following manganese injections for manganese-enhanced magnetic resonance imaging

In manganese-enhanced magnetic resonance imaging (MEMRI), the paramagnetic divalent ion of manganese (Mn²⁺) is injected into animals to generate tissue contrast, typically at much higher exposures than have been previously used in studies of Mn toxicity. Here we investigate the effect of these injections on the homeostasis of the transition metals iron and copper in mice to see if there are disruptions which should be considered in MEMRI studies. Manganese shares transport proteins with other transition metals including iron and copper, so it is possible that changes in manganese levels in tissue following injections of the metal may affect other metal levels too. This in turn may affect MRI contrast or the investigation of disease processes in the animal models being imaged. In this study, we measured manganese, iron, and copper concentrations in the blood, kidney, liver and in brain regions in mice treated with four injections of 30 mg/kg MnCl₂ 4H₂O (dry chemical weight/body weight)—a common dose used in MEMRI. In addition to the expected increases in manganese in tissues, we noted a statistically significant reduction in copper in the kidney and liver. Also, we noted a statistically significant decrease in concentration of iron in the thalamus of the brain. These findings suggest that the high doses of manganese injected in MEMRI studies can disrupt the homeostasis of other transition metals in mice.     

Transition metal homeostasis: from yeast to human disease

Transition metal ions are essential nutrients to all forms of life. Iron, copper, zinc, manganese, cobalt and nickel all have unique chemical and physical properties that make them attractive molecules for use in biological systems. Many of these same properties that allow these metals to provide essential biochemical activities and structural motifs to a multitude of proteins including enzymes and other cellular constituents also lead to a potential for cytotoxicity. Organisms have been required to evolve a number of systems for the efficient uptake, intracellular transport, protein loading and storage of metal ions to ensure that the needs of the cells can be met while minimizing the associated toxic effects. Disruptions in the cellular systems for handling transition metals are observed as a number of diseases ranging from hemochromatosis and anemias to neurodegenerative disorders including Alzheimer??s and Parkinson??s disease. The yeast Saccharomyces cerevisiae has proved useful as a model organism for the investigation of these processes and many of the genes and biological systems that function in yeast metal homeostasis are conserved throughout eukaryotes to humans. This review focuses on the biological roles of iron, copper, zinc, manganese, nickel and cobalt, the homeostatic mechanisms that function in S. cerevisiae and the human diseases in which these metals have been implicated.     

Effect of form of iron on nickel deprivation in the rat

In three fully crossed, factorially arranged, completely randomized experiments, female weanling rats were fed a basal diet (containing about 10 ng of nickel and 2.3 μg of iron/g) supplemented with graded levels of nickel and iron. Iron was supplemented to the diet in experiment 1 at levels of 0, 25, 50, and 100 μg/g as a mixture of 40% FeSO₄·nH₂O and 60% Fe₂(SO₄)₃·nH₂O; in experiment 2 at levels of 0, 12.5, 25, 50, and 100 μg/g as Fe₂(SO₄)₃·nH₂O; in experiment 3 at levels of 0, 25, and 50 μg/g as either the mixture of ferric-ferrous sulfates, or as ferric sulfate only. Nickel as NiCl₂·3H₂O was supplemented to the diet in experiment 1 at levels of 0, 5, and 50 μg/g; in experiment 2 at levels of 0 and 50 μg/g; and in experiment 3 at levels of 0 and 5 μg/g. Regardless of dietary nickel, rats fed no supplemental iron exhibited depressed iron content and elevated copper, manganese, and zinc contents in the liver. Nickel and iron did not interact to affect iron, manganese, and zinc in liver. Liver copper was inconsistently affected by an interaction between nickel and iron. Nickel deprivation apparently accentuated the elevation of the copper level in livers of severely iron-deficient rats. Experiment 3 showed that the form of dietary iron altered the effect of nickel deprivation on the iron content of the liver. When only ferric sulfate was supplemented to the diet, liver iron content was depressed in nickel-deprived rats. On the other hand, when the ferric-ferrous mixture was supplemented to the diet, nickel deprivation apparently elevated the iron content in the liver. The findings support the views that (1) parameters that are affected by an interaction between nickel and iron are limited in factorially arranged experiments, and (2) the form and level of dietary iron markedly influence the effect of nickel deprivation in the rat.     

Release of Metal Ions from Orthodontic Appliances: An In Vitro Study

In this paper, we report the results of an in vitro experiment on the release of metal ions from orthodontic appliances composed of alloys containing iron, chromium, nickel, silicon, and molybdenum into artificial saliva. The concentrations of magnesium, aluminum, silicon, phosphorus, sulfur, potassium, calcium, titanium, vanadium, manganese, iron, cobalt, copper, zinc, nickel, and chromium were significantly higher in artificial saliva in which metal brackets, bands, and wires used in orthodontics were incubated. In relation to the maximum acceptable concentrations of metal ions in drinking water and to recommended daily doses, two elements of concern were nickel (573 vs. 15 μg/l in the controls) and chromium (101 vs. 8 μg/l in the controls). Three ion release coefficients were defined: α, a dimensionless multiplication factor; β, the difference in concentrations (in micrograms per liter); and γ, the ion release coefficient (in percent). The elevated levels of metals in saliva are thought to occur by corrosion of the chemical elements in the alloys or welding materials. The concentrations of some groups of dissolved elements appear to be interrelated.     

Trace Metal Imaging of Sulfate-Reducing Bacteria and Methanogenic Archaea at Single-Cell Resolution by Synchrotron X-Ray Fluorescence Imaging

Metal cofactors are required for many enzymes in anaerobic microbial respiration. This study examined iron, cobalt, nickel, copper, and zinc in cellular and abiotic phases at the single-cell scale for a sulfate-reducing bacterium (Desulfococcus multivorans) and a methanogenic archaeon (Methanosarcina acetivorans) using synchrotron X-ray fluorescence microscopy. Relative abundances of cellular metals were also measured by inductively coupled plasma mass spectrometry. For both species, zinc and iron were consistently the most abundant cellular metals. M. acetivorans contained higher nickel and cobalt content than D. multivorans, likely due to elevated metal requirements for methylotrophic methanogenesis. Cocultures contained spheroid zinc sulfides and cobalt/copper sulfides.     

Heavy metal accumulation in wheat and barley: The effects of soil presence and liquid manure amendment

An experiment was undertaken to evaluate the effect of liquid manure amendment on heavy metal accumulation in wheat and barley. For this purpose, both kinds of seedlings were grown simultaneously in a Petri dish, while wheat seedlings were also grown in pots containing unpolluted agricultural soil. All of the seedlings were irrigated with one of the three prepared solutions: artificial rainwater solution, heavy metal solution and liquid manure solution containing NH₄NO₃, H₃PO₄ and KOH along with equal amounts of heavy metals as in the second solution. Twenty days later, 1 g of plant tissue was digested with the mixture of HNO₃ and H₂O₂ for ICP-OES/HG-ICP-OES analysis. The results showed that the uptake of arsenic and mercury was highest for both plants grown in a Petri dish. Furthermore, the wheat grown in a Petri dish also had a high content of nickel, cadmium and copper, while the pot-grown wheat contained high amounts of iron and manganese, probably due to the adsorption of nickel, cadmium, copper and mercury on soil phases. The lower uptake of all heavy metals was observed after the amendment of liquid manure, with the exception of manganese in wheat and mercury in all plants.     

Resistance of <Emphasis Type="Italic">Acidiplasma</Emphasis> archaea to heavy metal ions

Effect of the ions of heavy metals (copper, zinc, and nickel) on growth of and ferrous iron oxidation by extremely acidophilic archaeal strains of the genus Acidiplasma (Acidiplasma sp. MBA-1; A. aeolicum V1^T; and A. cupricumulans BH2^T) was studied. Effect of the metals depending on their concentration was studied within the range from 5 to 1000 mM. All studied strains were able to oxidize iron in the presence of the highest tested heavy metal concentrations (1000 mM). All metal ions had, however, a noticeable inhibitory effect both on both growth and on iron oxidation. The lowest concentrations of copper, zinc, and nickel partially suppressing microbial growth were determined (5, 10, and 5 mM, respectively). These findings are of interest, since almost no literature data on resistance of Acidiplasma archaea to heavy metals are available, although these prokaryotes are among the most important groups of microorganisms used in biohydrometallurgy.     

Characterizing the genetic basis of copper toxicity in Drosophila reveals a complex pattern of allelic,regulatory, and behavioral variation

A range of heavy metals are required for normal cell function and homeostasis. However, the anthropogenic release of metal compounds into soil and water sources presents a pervasive health threat. Copper is one of many heavy metals that negatively impacts diverse organisms at a global scale. Using a combination of quantitative trait locus (QTL) mapping and RNA sequencing in the Drosophila Synthetic Population Resource, we demonstrate that resistance to the toxic effects of ingested copper in D. melanogaster is genetically complex and influenced by allelic and expression variation at multiple loci. QTL mapping identified several QTL that account for a substantial fraction of heritability. Additionally, we find that copper resistance is impacted by variation in behavioral avoidance of copper and may be subject to life-stage specific regulation. Gene expression analysis further demonstrated that resistant and sensitive strains are characterized by unique expression patterns. Several of the candidate genes identified via QTL mapping and RNAseq have known copper-specific functions (e.g., Ccs, Sod3, CG11825), and others are involved in the regulation of other heavy metals (e.g., Catsup, whd). We validated several of these candidate genes with RNAi suggesting they contribute to variation in adult copper resistance. Our study illuminates the interconnected roles that allelic and expression variation, organism life stage, and behavior play in copper resistance, allowing a deeper understanding of the diverse mechanisms through which metal pollution can negatively impact organisms.     

Seasonal variation in trace metal concentrations in three talitrid amphipods from the Gulf of Gdansk, Poland

Talitrid amphipod crustaceans are increasingly being used as biomonitors of trace metal bioavailabilities in coastal waters, and it is important to understand how other factors, in addition to metal pollution, might affect their accumulated body concentrations. Seasonal variation (April-October 2000) in body concentrations of copper, zinc, cadmium, iron, manganese, lead and nickel has been investigated in three species, Orchestia cavimana, Talitrus saltator and Talorchestia deshayesii, from the region of the Gulf of Gdansk (including the Vistula Lagoon), Poland, an area with considerable temperature variation between summer and winter. Seasonal variation in the body metal concentrations of talitrid amphipod crustaceans was confirmed in each population, but only copper showed a consistent pattern. Copper concentrations fell from early to late summer, perhaps either as a result of the replacement of the older overwintering generation by the younger spring one, or as a result of the loss of haemocyanin in autumn amphipods entering a period of low metabolic activity. Metal concentration data for T. saltator from Gdynia-Osada Rybacka compared with equivalent data for 1996 and 1998 show a significant drop in metals associated with the influx of the Vistula river water, which occurred in 1998, following a major flood event in 1997.     

The interplay between siderophore secretion and coupled iron and copper transport in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120

Iron uptake is essential for Gram-negative bacteria including cyanobacteria. In cyanobacteria, however, the iron demand is higher than in proteobacteria due to the function of iron as a cofactor in photosynthesis and nitrogen fixation, but our understanding of iron uptake by cyanobacteria stands behind the knowledge in proteobacteria. Here, two genes involved in this process in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 were identified. ORF all4025 encodes SchE, a putative cytoplasmic membrane-localized transporter involved in TolC-dependent siderophore secretion. Inactivation of schE resulted in an enhanced sensitivity to high metal concentrations and decreased secretion of hydroxamate-type siderophores. ORF all4026 encodes a predicted outer membrane-localized TonB-dependent iron transporter, IacT. Inactivation of iacT resulted in decreased sensitivity to elevated iron and copper levels. Expression of iacT from the artificial trc promoter (P_trc) resulted in sensitization against tested metals. Further analysis showed that iron and copper effects are synergistic because a decreased supply of iron induced a significant decrease of copper levels in the iacT insertion mutant but an increase of those levels in the strain carrying P_trc-iacT. Our results unravel a link between iron and copper homeostasis in Anabaena sp. PCC 7120.     

Co-occurrence of antibiotic,biocide, and heavy metal resistance genes in bacteria from metal and radionuclide contaminated soils at the Savannah River Site

Contaminants such as heavy metals may contribute to the dissemination of antimicrobial resistance (AMR) by enriching resistance gene determinants via co-selection mechanisms. In the present study, a survey was performed on soils collected from four areas at the Savannah River Site (SRS), South Carolina, USA, with varying contaminant profiles: relatively pristine (Upper Three Runs), heavy metals (Ash Basins), radionuclides (Pond B) and heavy metal and radionuclides (Tim’s Branch). Using 16S rRNA gene amplicon sequencing, we explored the structure and diversity of soil bacterial communities. Sites with legacies of metal and/or radionuclide contamination displayed significantly lower bacterial diversity compared to the reference site. Metagenomic analysis indicated that multidrug and vancomycin antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) including those associated with copper, arsenic, iron, nickel and zinc were prominent in all soils including the reference site. However, significant differences were found in the relative abundance and diversity of certain ARGs and MRGs in soils with metal/radionuclide contaminated soils compared to the reference site. Co-occurrence patterns revealed significant ARG/MRG subtypes in predominant soil taxa including Acidobacteriaceae, Bradyrhizobium, Mycobacterium, Streptomyces, Verrumicrobium, Actinomadura and Solirubacterales. Overall, the study emphasizes the potential risk of human activities on the dissemination of AMR in the environment.     

Photosynthetic and biochemical responses of the freshwater green algae <Emphasis Type="Italic">Closterium ehrenbergii</Emphasis> Meneghini (Conjugatophyceae) exposed to the metal coppers and its implication for toxicity testing

The freshwater green algae Closterium is sensitive to water quality, and hence has been suggested as ideal organisms for toxicity testing. In the present study, we evaluated the photosynthetic and biochemical responses of C. ehrenbergii to the common contaminants, coppers. The 72 h median effective concentrations (EC₅₀) of CuSO₄ and CuCl₂ on the test organism were calculated to be 0.202 mg/L and 0.245 mg/L, respectively. Exposure to both coppers considerably decreased pigment levels and photosynthetic efficiency, while inducing the generation of reactive oxygen species (ROS) in cells with increased exposure time. Moreover, the coppers significantly increased the levels of lipid peroxidation and superoxide dismutase (SOD) activity, even at relatively lower concentrations. These suggest that copper contaminants may exert deleterious effects on the photosynthesis and cellular oxidative stress of C. ehrenbergii, representing its powerful potential in aquatic toxicity assessments.     

Comparisons of nine heavy metals in salt gland and liver of greater scaup (Aythya marila), black duck (Anas rubripes) and mallard (A. platyrhynchos)

Levels of nine heavy metals were measured in the livers and salt glands of greater scaup (Aythya marila), black duck (Anas rubripes) and mallard (A. platyrhynchos) from Raritan Bay, New Jersey to determine if the functioning avian salt gland concentrates heavy metals. Heavy metals examined were cadmium, cobalt, chromium, copper, lead, mercury, manganese, nickel and zinc. Heavy metal levels varied significantly by species and tissue for chromium, copper, lead, and manganese, and by tissue for cobalt, mercury, nickel and zinc. In comparing tissues cobalt was higher in the salt glands than in livers of all three species; chromium and nickel were higher in the salt gland than liver for mallard and black duck; and lead, manganese and zinc were higher in the liver than the salt gland in greater scaup. Generally metal levels were higher in the salt gland for mallard and black duck, and in the liver for greater scaup.     

Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn²⁺ complex of this ligand was the most potent with IC₅₀s of 0.127 and 0.157 μM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn²⁺. Few of the Cu²⁺ and Fe²⁺ complexes also showed improvement in activity but Ni²⁺, Co²⁺ and Zn²⁺ complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development.     

Seminal plasma trace metal levels in industrial workers

This study compares the seminal plasma trace metal levels of hospital workers with groups of industrial workers in a petroleum refinery, smelter, and chemical plant. The metals measured were the essential metals (copper, zinc, nickel, cobalt, and manganese) and the toxic metals (lead, cadmium, and aluminum). The group mean±SE metal level for each group (50 subjects per group) was calculated, and the statistical significance of the group mean differences of the industrial groups with the hospital group (control) was determined by the Student’s t-test. The differences observed in the smelter group were increased copper and zinc (p≤0.001) and decreased nickel, cobalt, and manganese (p≤0.001,≤0.01). The refinery group differences were increased copper, zinc, and nickel (p≤0.001) but decreased cobalt and manganese (p≤0.001). The chemical group differences were increased zinc (p≤0.001) and decreased cobalt (p≤0.001). The seminal plasma levels of the toxic metals lead and aluminum were increased in each of the industrial groups (p≤0.001). Concurrent differences were (1) decreased accumulation of nickel, cobalt, and manganese in the smelter group, (2) decreased cobalt and managanese in the refinery group, and (3) only decreased cobalt in the chemical group.     

Biosynthesis of chemical compounds by Candida albicans and Candida glabrata

BackgroundIn the last three decades the species of Candida have been of great interest due to the high mortality rates that they cause in immunocompromised and hospitalized patients. These species are opportunistic pathogens and they have inhabited other environments long before colonizing human cells. Among these environments we find wastewater from mines, and water from aquifers and soils that contain high concentrations of precious metals as well as toxic and base metals.AimsThe aim of this study was to assess whether Candida albicans and Candida glabrata are able to maintain homeostasis in the presence of zinc, copper, cobalt or silver.MethodsTo achieve the objective, each of the Candida species was exposed to every single metal individually in a salt solution. Subsequently the treated cells were lysed to evaluate the compounds formed by means of Scanning Electron Microscopy-Energy Dispersive X-ray spectroscopy (SEM-EDS).ResultsWhen analyzing the compounds that both C. albicans and C. glabrata formed in the presence of each of the metals, we found that they had synthesized silver sulfide (Ag₂S), cobalt sulfate (CoSO₄), zinc phosphate (Zn₃(PO₄)₂), or copper oxide (CuO).ConclusionsOur results indicate that both C. albicans and C. glabrata have enzymatic and non-enzymatic mechanisms that allow them to achieve homeostasis in a different specific manner for each of the single metals to which they were exposed. To our knowledge, this is the first work reporting that C. albicans and C. glabrata can reduce different metals, with the subsequent formation of sulfides, sulfates, phosphates and oxides. This ability, developed over time by these Candida species, is probably a kind of biochemical mechanism in order to survive and colonize many different environments, from water or soil to humans. For this reason, C. albicans and C. glabrata make up an excellent model of study, both from a medical and biotechnical point of view.     

Influence of soil waterlogging on subsequent plant growth and trace metal content

Summary The uptake of trace metals by two plant species (French bean and maize) has been measured on two soils subjected to various waterlogging regimes. Uptake of both manganese and iron was increased due to soil waterlogging, although reoxidation of the soil affected iron more than manganese. Zinc and copper uptake was influenced by a species factor; French bean (Phaseolus vulgaris) showed preferential uptake of zinc, whereas maize (Zea mays) took up copper preferentially. Uptake of cobalt by both species was increased due to waterlogging, following the pattern of manganese.The abilities of these species to take up trace metals from soil followed the pattern predicted by selective extraction of soil for manganese, iron and cobalt, but not for zinc and copper.     

The Effects of Manganese (II) But Not Nickel (II) Ions on Enterococcus hirae Cell Growth, Redox Potential Decrease, and Proton-Coupled Membrane Transport

Enterococcus hirae grow well under anaerobic conditions by fermenting glucose, accompanied with the decrease of oxidation–reduction potential (E _h) from positive values to negative ones. It was shown that heavy metals—copper and iron ions—affect E. hirae growth and alter E _h and proton-potassium ions fluxes through the cell membrane. The aim of this study was to establish the effects of manganese (II) ions on bacterial growth within the concentration range of 0.01–1 mM and compare with nickel (II) ions’ effect. The presence of Mn²⁺ during E. hirae ATCC9790 growth had significant effects: The lag phase duration decreased while the specific growth rate was increased; decrease in E _h was shifted. In contrast, no visible changes in bacterial growth and E _h were observed in the case of Ni²⁺. The effects of these ions on proton-potassium ions fluxes through the cell membrane were estimated in the presence and absence of N,N′-dicyclohexylcarbodiimide (DCCD), inhibitor of the F_oF₁ ATPase. Stronger effect of Mn²⁺ on H⁺–K⁺ exchange was detected in the presence of DCCD that can be explained by a possible complex formation between these substances and its direct influence on membrane transport proteins.     

Uptake of six heavy metals by oat as influenced by soil type and additions of cadmium,lead, zinc and copper

Summary The influence of heavy metal additions on availability and uptake of cadmium, lead, zinc, copper, manganese and iron by oat was studied. The experiments were carried out as pot experiments using sandy loam, sandy soil and organic soil. Selective extractants were used to remove metals held in different soil fractions.Lead and copper were preferently bound by organics and oxides, zinc by oxides and inorganics, and cadmium by inorganics and organics.Addition of cadmium to the soils resulted in higher cadmium concentrations in all plant parts but lower concentrations of lead, zinc, copper, manganese and iron, and the accumulation indexes of these metals were also lower when cadmium was added to the soil.Addition of cadmium plus lead, zinc and copper resulted in higher cadmium concentrations in leaves and straw of plants grown in sandy loam and sandy soil, but lower concentrations when plants were grown in organic soil as compared with the results when cadmium was added separately. The transfer of cadmium, lead, zinc and copper from soil to plant was greatest from sandy soil, and zinc and cadmium were more mobile in the plant than were lead and copper.Cadmium concentrations in leaves correlated significantly with CaCl₂ and CH₃COOH extractions in sandy loam and sandy soil and with CH₃COOH extractions in organic soil.Generally, the total metal uptake was lowest from organic soil.