Metabolism Of Essential Metals Research Articles

Perinatal and early-life cobalt exposure impairs essential metal metabolism in immature ICR mice

The objective of the present study was to assess the impact of cobalt (Co) exposure on tissue distribution of iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn), as well as serum hepcidin levels in immature mice (18, 25, 30 days). Pregnant mice were exposed to 75 mg/kg b.w. cobalt chloride (CoCl2 × 6H2O) with drinking water starting from 3 days before delivery and during lactation. At weaning (day 25) the offspring were separated and housed in individual cages with subsequent exposure to 75 mg/kg b.w. CoCl2 until 30 days postnatally. Evaluation of tissue metal levels was performed by an inductively coupled plasma-mass spectrometry (ICP-MS). Serum hepcidin level was assayed by enzyme linked immunosorbent assay (ELISA). Cobalt exposure resulted in a time- and tissue-dependent increase in Co levels in kidney, spleen, liver, muscle, erythrocytes, and serum on days 18, 25, and 30. In parallel with increasing Co levels, CoCl2 exposure resulted in a significant accumulation of Cu, Fe, Mn, and Zn in the studied tissues, with the effect being most pronounced in 25-day-old mice. Cobalt exposure significantly increased serum hepcidin levels only in day18 mice. The obtained data demonstrate that Co exposure may alter essential metal metabolism in vivo.

Elevated non-essential metals and the disordered metabolism of essential metals are associated to abnormal pregnancy with spontaneous abortion

Spontaneous abortion is a considerable threat to the physiology and mental health of the mother. The etiology of spontaneous abortion is multifactorial with complicated mechanisms, of which overexposure to non-essential metals (especially heavy metals) has been proposed to be associated with adverse birth outcomes. However, significant knowledge gaps remain to be filled in, such as the deleterious profile of non-essential metals and their interplay with essential metals in abnormal pregnancy. Under this setting, we aimed to address these challenges by conducting a cross-sectional study on 56 patients with spontaneous abortion in the 1st trimester, by comparing to 55 healthy pregnant women in 1st the trimester and 41 non-pregnant healthy women. Overexposure to a few non-essential metals, such as arsenic (As), antimony (Sb) and bismuth (Bi), was found in patients with spontaneous abortion, and likewise, some essential elements, such as magnesium (Mg), copper (Cu), vanadium (V), strontium (Sr) and tin (Sn), were also found to be elevated under spontaneous abortion. Further evidence of abnormal pregnancy was induced by a reduced level of internal hormones necessary for normal gestation, such as estradiol (E2) and progesterone (PRGE) in women with spontaneous abortion. Lactate dehydrogenase (LDH) and thyroid-stimulating hormone (TSH) levels were slightly increased in patients with spontaneous abortion. Comprehensive correlation analyses were carried out to identify the crucial factors that result in abortion. Our data stratified the important variables in decreasing order: PRGE, As, Mg, Sb, Sr, Sn, Bi and pregnant times in the progress of spontaneous abortion. Moreover, labyrinthine associations were uncovered between PRGE, non-essential metals and essential elements in causing spontaneous abortion. Therefore, our combined data unveiled the likely synergistic implications of elevated non-essential metals and the disordered metabolism of essential metals in abnormal pregnancy.

Insights into the accumulation and transformation of Ch-SeNPs by Raphanus sativus and Brassica juncea: Effect on essential elements uptake

Selenium (Se) at very low doses has important functions for humans. Unfortunately, the low levels of Se in soils in various regions of the world have implemented the agronomic biofortification of crops by applying Se-enriched fertilizers (mainly based on selenate). Lately, the use of nanofertilizers is growing in interest as their low size reduces the amount of chemicals and minimizes nutrient losses in comparison with conventional bulk fertilizers. However, the knowledge on their fate and environmental impact is still scarce. This study aims to evaluate the biotransformation of chitosan-modified Se nanoparticles (Ch-SeNPs) as well as their effect on the metabolism of essential metals (Fe, Cu, Zn and Mo) when applied to hydroponic cultivation of R. sativus and B. juncea. In house-synthesized Ch-SeNPs were characterized in both synthesis and hydroponic culture media by transmission electron microscopy (TEM), dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). The composition of one-tenth strength Hoagland's solution did not affect the size, shape and concentration in number of particles per mL of Ch-SeNPs. The plants were grown inside a box at 25 °C during the months of May–July in 2018. After a week of treatment with Ch-SeNPs, plants were harvested and divided into roots and aerial part. The biotransformation of Ch-SeNPs was evaluated through a process of enzymatic hydrolysis and subsequent analysis by HPLC-ICP-MS and HPLC-ESI-MS/MS. The results confirmed the transformation of Ch-SeNPs to seleno-amino acids: Selenomethionine (SeMet), Semethylselenocysteine (SeMetSeCys) and ɣ-glutamyl-Se-MetSeCys. Moreover, Multiple-way analysis of variance (ANOVA) and principal component analysis (PCA) showed that, regardless the plant species, Ch-SeNPs supplementation affected the absorption of Zn.

Metallothionein in Brain Disorders.

Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV), three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.

Antimicrobial Action of Chelating Agents: Repercussions on the Microorganism Development, Virulence and Pathogenesis

Infections caused by resistant microorganisms often fail to respond to conventional therapy, resulting in prolonged illness, increased treatment costs and greater risk of death. Consequently, the development of novel antimicrobial drugs is becoming more demanding every day since the existing drugs either have too many side-effects or they tend to lose effectiveness due to the selection of resistant strains. In view of these facts, a number of new strategies to obstruct vital biological processes of a microbial cell have emerged; one of these is focused on the use of metal-chelating agents, which are able to selectively disturb the essential metal metabolism of the microorganism by interfering with metal acquisition and bioavailability for crucial reactions. The chelation activity is able to inhibit the biological role of metal-dependent proteins (e.g., metalloproteases and transcription factors), disturbing the microbial cell homeostasis and culminating in the blockage of microbial nutrition, growth and development, cellular differentiation, adhesion to biotic (e.g., extracellular matrix components, cell and/or tissue) and abiotic (e.g., plastic, silicone and acrylic) structures as well as controlling the in vivo infection progression. Interestingly, chelating agents also potentiate the activity of classical antimicrobial compounds. The differences between the microorganism and host in terms of the behavior displayed in the presence of chelating agents could provide exploitable targets for the development of an effective chemotherapy for these diseases. Consequently, metal chelators represent a novel group of antimicrobial agents with potential therapeutic applications. This review will focus on the anti-fungal and anti-protozoan action of the most common chelating agents, deciphering and discussing their mode of action.

Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population

Metallothioneins (MTs) are metal-binding, low molecular weight proteins and are involved in pathophysiological processes like metabolism of essential metals, metal ion homeostasis and detoxification of heavy metals. Metallothionein expression is induced by various heavy metals especially cadmium, mercury and zinc; MTs suppress toxicity of heavy metals by binding themselves to these metals. The aim of this study was to investigate the association between the − 5 A/G metallothionein 2A (MT2A) single nucleotide polymorphism (SNP) and Cd, Zn and Cu levels in the renal cortex from autopsy cases. MT2A core promoter region − 5 A/G SNP was analyzed by PCR-RFLP method using 114 autopsy kidney tissues and the genotype frequencies of this polymorphism were found as 87.7% homozygote typical (AA), 11.4% heterozygote (AG) and 0.9% homozygote atypical (GG). In order to assess the Cd, Zn and Cu levels in the same autopsy kidney tissues, a dual atomic absorption spectrophotometer system was used and the average levels of Cd, Zn and Cu were measured as 95.54 ± 65.58 µg/g, 181.20 ± 87.72 µg/g and 17.14 ± 16.28 µg/g, respectively. As a result, no statistical association was found between the − 5 A/G SNP in the MT2A gene and the Zn and Cu levels in the renal cortex ( p > 0.05), but considerably high accumulation of Cd was monitored for individuals having AG (151.24 ± 60.21 µg/g) and GG genotypes (153.09 µg/g) compared with individuals having AA genotype (87.72 ± 62.98 µg/g) ( p < 0.05). These results show that the core promoter region polymorphism of metallothionein 2A increases the accumulation of Cd in human renal cortex.

Impact of digenean parasite infection on metallothionein synthesis by the cockle ( Cerastoderma edule): A multivariate field monitoring

Metallothioneins (MT) are proteins that play an important role in metabolism of essential metals and detoxification of trace metals from living organisms. Their synthesis is induced by metal pollution but can also be exacerbated by other factors such as reproduction processes. In this context, we monitored MT concentrations in a cockle Cerastoderma edule (marine bivalve) population and highlighted the effect of a castrating digenean parasite, Labratrema minimus. In spent cockles, MT levels were low (ca. 5 nmol sites g −1, fresh weight) but slightly higher in parasitized individuals. During gametogenesis, MT synthesis increased in all cockles, but concentrations were lower in parasitized individuals (18 against 27 nmol sites g −1, fw in unparasitized cockles) in relation with gonad damage by parasites. Therefore, it is suggested that parasite infection in cockles can modulate MT synthesis that could consequently interfere with the response of these protective proteins in case of metal contamination.

Antioxidant function of metallothioneins

Since the discovery of metallothionein in 1957, it has been accepted that the primary roles of this protein are: 1) detoxification of heavy metals, and 2) regulation of the metabolism of essential metals. Recently, studies have suggested an additional role for metallothionein as a free radical scavenger. This article reviews in vitro and in vivo evidence which supports the role for metallothionein in modulation of reactive oxygen species. J. Trace Elem. Exp. Med. 11:219–226, 1998. © 1998 Wiley-Liss, Inc.

In vitro trypanocidal activity of tetraethylthiuram disulfide and sodium diethylamine-N-carbodithioate on Trypanosoma cruzi.

Tetraethylthiuram disulfide (disulfiram) (TETD) and sodium diethylamine-N-carbodithioate (DECD) were examined for their in vitro trypanocidal activity against Trypanosoma cruzi. Benznidazole (BNZ), the drug used clinically for the chemotherapy of Chagas' disease, was used as a positive control. Inhibition assays included evaluation against the epimastigote, trypomastigote, and amastigote forms. Tetraethylthiuram disulfide and its reductive metabolite DECD inhibited 64.6% and 69.7%, respectively, of epimastigotes at a concentration of 50 micrograms/ml after 72 hr and BNZ caused 69.1% inhibition at the same concentration. Both TETD and DECD were not as effective against tissue culture trypomastigotes as BNZ (TETD = 47.7%,; DECD = 46.1%; BNZ = 88.7%) at 50 micrograms/ml after 24 hr. However, TETD and DECD treatment of amastigote-infected 3T3 fibroblasts yielded 60 and 67% inhibition, respectively, as compared to BNZ with an inhibition of 62%. A possible mechanism of action of TETD and DECD is via interference with the essential metal metabolism of T. cruci. Since toxicity data for both TETD and DECD are available and both drugs are active against the parasite, these drugs are candidates for further study to determine if they are of potential clinical interest as a prophylactic or therapeutic agent against Chagas' disease.

Chelating agent inhibition of Trypanosoma cruzi epimastigotes In vitro

A number of chelating agents and some of their derivatives are as effective as, or superior to, benznidazole, the compound currently in clinical use, in the suppression of the reproduction of epimastigotes of Trypanosoma cruzi, the protozoa that causes Chagas' disease. All compounds were examined at a culture concentration of 5 μg/mL. The most effective compounds included N, N, N′, N′-tetrakis(2-pyridylmethyl)ethylenediamine, sodium diethylamine- N-carbodithioate, piperidine- N-carbodithioate and several of its analogs, a number of other carbodithioates with two nonpolar groups on the nitrogen, and tetraethylthiuram disulfide, a prodrug of sodium diethylamine- N-carbodithioate and widely used in the treatment of alcoholism. The introduction of additional ionic or nonionic polar groups on the chelating molecule generally results in a loss of tyrpanocidal activity. Common commercially available chelating agents which exhibited no activity included d-penicillamine, meso-2,3-dimercaptosuccinic acid, and triethylenetetramine tetrahydrochloride. Dose-response data on the culture indicated that some of these compounds exhibited inhibition of Trypanosoma cruzi epimastigotes at concentrations as low as 0.625 μg/mL. It is proposed that the mechanism of action of these compounds is based on their ability to interface with the essential metal metabolism at intracellular sites of the epimastigote involving iron, copper, or zinc. The results also indicate that a certain degree of hydrophobicity may be necessary for the groups attached to the literal metal-bonding structure if the compounds are to successfully inhibit the epimastigotes of Trypanosoma cruzi. The development of antiprotozoal drugs which are chelating agents specifically designed to selectively disrupt the essential metal metabolism of Trypanosoma cruzi should furnish a new generation of drugs which can be used in the treatment of Chagas' disease.

Ultrastructural and histochemical aspects of zinc accumulation by fish scales

The effect of zinc exposure on the ultrastructure of the scales and scale associated cells of the estuarine teleost, Fundulus heteroclitus was investigated in laboratory experiments. The Timm sulfide silver stain indicated that in the calcified region of the scales, Zn was colocalized with the calcium phosphate mineral crystals. X-ray diffraction analysis showed that Zn did not have an effect on crystal structure. The scale osteoblasts of Zn-exposed fish showed an increase in the number of lysosome-like structures contained by the cytoplasm. In Zn-exposed animals, X-ray microanalysis revealed that these structures contain greatly increased levels of zinc and sulfur relative to controls. In all specimens, the lysosomes contained higher levels of Zn than either the surrounding cytoplasm or adjacent scales. The findings suggest that osteoblast lysosomes may be involved in the accumulation of Zn and other metals by fish scales by the enzymatic degradation of metallothioneins or other metal-binding proteins. This could represent an important mechanism for the detoxification of excess heavy metal ions taken up from the environment and the metabolism of essential metals by calcified tissues.

ＶＸ２がん上がくどう移植家ウサギにおけるしゅようおよびけい部リンパ節の分析電子顕微鏡所見について

The essential metal metabolism of the neoplastic disease has been investigated on its serum level and isoenzyme. There are few reports on the essential elements analysis of the neoplastic tissue, muscle and lymphonodes.The VX2 carcinoma, transplanted into the maxillary sinus of the domestic rabbits, was prepared for the research of the findings of the microscope, scanning electron microscope and X-ray microanalyzer (XMA).The movement of phosphate and karium had little change and showed the reverse peak between the controled muscle and the tumor. The local lymphonode of the rabbit, bearing the tumor at the maxillary sinus, indicated almost the same pattern in each lymphonode on the XMA findings. The karium in the lymphonode showed the highest peak at the inner layer of the vessel.

Generalized seizures alter the cerebral and peripheral metabolism of essential metals in mice

The effects of seizures on the cerebral and peripheral metabolism of essential metals were studied in mice. Acute and chronic seizures were produced either by electroshock (ES) or by a systemic convulsant. Organ and subcellular distribution of 54Mn and 65Zn were determined prior to and at different intervals after seizure cessation. In mice shocked for 21 days, the concentrations of manganese, zinc, magnesium, and copper were determined in selected tissues. Sham-seizured mice served as controls. When 54Mn was injected after a single ES, the isotope's retention increased in the liver by 67% ( P < 0.01) and decreased in the brain and carcass by 53 and 42%, respectively ( P < 0.01). Repeated ES further augmented these effects ( P < 0.01). These changes diminished as a function of time to the animal's recovery from ES. Liver and regional brain fractionations revealed significant perturbation in the intercellular partition of 54Mn, suggesting increased metal utilization. Brain and liver 65Zn were not affected by ES. Manganese content increased in the liver by 67% ( P < 0.01) and decreased in whole brain by 16.5% ( P < 0.01), after chronic ES. Cortical manganese and hypothalamic magnesium were the principal sites of loss. Small (12 to 13%), but significant elevations of magnesium were found in liver and skeletal muscle ( P < 0.05). Copper increased in muscle by 26% ( P < 0.02). Seizures selectively altered the normal brain and extracerebral distribution of essential metals which may lead to regional metal deficiency or excess. These changes were linked to the metabolic consequences of convulsive activity and may be relevant to seizure control and electroshock therapy in man.

Factors Influencing Metabolism and Toxicity of Metals: A Consensus Report

The relationships between metals like lead, cadmium, and mercury and other factors that quantitatively and qualitatively modify their metabolism and toxicity are surveyed. Interactions are examined by scientists from a variety of fields covering biochemistry, ecology, epidemiology, nutrition, occupational health, and toxicology. Evidence of interactions among arsenic, cadmium, lead, and mercury, and between these elements and selenium, calcium, copper, zinc, and iron is considered. There is ample evidence from animal experiments that many interactions occur. The enhancing influence of marginal essential element intake on cadmium absorption and the deleterious effects of cadmium on essential metal metabolism may have public health implications in populations with borderline dietary status. The possibility of interaction between irritating substances, like tobacco smoke, and the toxicity of metals is discussed. (312 references)