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Toxic and Essential Metals in Human Health and Disease

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A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 65483

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Prof. Dr. Valeria M. Nurchi

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Department of Environmental and Life Science, Università degli Studi di Cagliari, Cagliari, Italy
Interests: analytical chemistry; solution equilibria; bioinorganic chemistry; chelating agents; toxic metal ions; environmental chemistry
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Jan Aaseth

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Department of Research, Innlandet Hospital, N-2381 Brumunddal, Norway
Interests: internal medicine; endocrinology; toxicology; neurodegenerative diseases; neuroimaging; bioinorganic chemistry; environmental chemistry; medicinal chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In this Special Issue of Biomolecules called “Toxic and Essential Metals in Human Health and Disease”, ; we would like to explore the physicochemical and biological aspects of the elements, both in terms of the expanding appreciation of the essentiality of individual elements and the toxicity of excessive amounts of each element. Molecular biologists and enzyme chemists share with clinicians and toxicologists an appeciation of these substances. The nutritional and metabolic complexities of the trace and mineral elements are reflected by the diversity of conditions recognized as being affected by derangements or deficiencies of these substances, such as for instance neurodegenerative diseases, dermatological conditions, carcinogenic processes, cancer, osteoporosis, cardiovascular diseases, and endocrine dysfunctions. The ability of some trace elements to interfere with the biochemical and physiological utilization of molecular oxygen continues to sustain considerable research interest.

The journal Biomolecules welcomes reseachers and clinicians around the world to submit for online presentation their results or reviews within this field of Toxic and Essential Metals in Human Health and Disease in this Special Issue.

Prof. Valeria M Nurchi
Prof. Jan Aaseth
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

essential elements
metal toxicity
neurotoxicology
chelation therapy
medicinal chemistry
carcinogenesis
cardiovascular diseases

Published Papers (14 papers)

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Research

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16 pages, 1054 KiB

Open AccessArticle

Interaction between Polyphenolic Antioxidants and Saccharomyces cerevisiae Cells Defective in Heavy Metal Transport across the Plasma Membrane

by Lavinia Liliana Ruta and Ileana Cornelia Farcasanu

Biomolecules 2020, 10(11), 1512; https://doi.org/10.3390/biom10111512 - 4 Nov 2020

Cited by 7 | Viewed by 1971

Abstract

Natural polyphenols are compounds with important biological implications which include antioxidant and metal-chelating characteristics relevant for their antimicrobial, antitumor, or antiaging potential. The mechanisms linking polyphenols and heavy metals in their concerted actions on cells are not completely elucidated. In this study, we used the model eukaryotic microorganism Saccharomyces cerevisiae to detect the action of widely prevalent natural polyphenols on yeast cells defective in the main components involved in essential heavy metal transport across the plasma membrane. We found that caffeic and gallic acids interfered with Zn accumulation, causing delays in cell growth that were alleviated by Zn supplementation. The flavones morin and quercetin interfered with both Mn and Zn accumulation, which resulted in growth improvement, but supplemental Mn and especially Zn turned the initially benefic action of morin and quercetin into potential toxicity. Our results imply that caution is needed when administering food supplements or nutraceuticals which contain both natural polyphenols and essential elements, especially zinc. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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21 pages, 2210 KiB

Open AccessArticle

8-Hydroxyquinoline-2-Carboxylic Acid as Possible Molybdophore: A Multi-Technique Approach to Define Its Chemical Speciation, Coordination and Sequestering Ability in Aqueous Solution

by Katia Arena, Giuseppe Brancato, Francesco Cacciola, Francesco Crea, Salvatore Cataldo, Concetta De Stefano, Sofia Gama, Gabriele Lando, Demetrio Milea, Luigi Mondello, Alberto Pettignano, Winfried Plass and Silvio Sammartano

Biomolecules 2020, 10(6), 930; https://doi.org/10.3390/biom10060930 - 18 Jun 2020

Cited by 5 | Viewed by 3115

Abstract

8-hydroxyquinoline-2-carboxylic acid (8-HQA) has been found in high concentrations (0.5–5.0 mmol·dm⁻³) in the gut of Noctuid larvae (and in a few other lepidopterans), in which it is proposed to act as a siderophore. Since it is known that many natural siderophores are also involved in the uptake and metabolism of other essential elements than iron, this study reports some results on the investigation of 8-HQA interactions with molybdate (MoO₄²⁻, i.e., the main molybdenum form in aqueous environments), in order to understand the possible role of this ligand as molybdophore. A multi-technique approach has been adopted, in order to derive a comprehensive set of information necessary to assess the chemical speciation of the 8-HQA/MoO₄²⁻ system, as well as the coordination behavior and the sequestering ability of 8-HQA towards molybdate. Chemical speciation studies have been performed in KCl_(aq) at I = 0.2 mol·dm⁻³ and T = 298.15 K by ISE-H⁺ (glass electrode) potentiometric and UV/Vis spectrophotometric titrations. CV (Cyclic Voltammetry), DP-ASV (Differential Pulse-Anodic Stripping Voltammetry), ESI-MS experiments and quantum mechanical calculations have been also performed to derive information about the nature and possible structure of species formed. These results are also compared with those reported for the 8-HQA/Fe³⁺ system in terms of chemical speciation and sequestering ability of 8-HQA. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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19 pages, 3188 KiB

Open AccessArticle

Redox-Dependent Copper Ion Modulation of Amyloid-β (1-42) Aggregation In Vitro

by Nima Sasanian, David Bernson, Istvan Horvath, Pernilla Wittung-Stafshede and Elin K. Esbjörner

Biomolecules 2020, 10(6), 924; https://doi.org/10.3390/biom10060924 - 18 Jun 2020

Cited by 16 | Viewed by 3738

Abstract

Plaque deposits composed of amyloid-β (Aβ) fibrils are pathological hallmarks of Alzheimer’s disease (AD). Although copper ion dyshomeostasis is apparent in AD brains and copper ions are found co-deposited with Aβ peptides in patients’ plaques, the molecular effects of copper ion interactions and redox-state dependence on Aβ aggregation remain elusive. By combining biophysical and theoretical approaches, we here show that Cu²⁺ (oxidized) and Cu⁺ (reduced) ions have opposite effects on the assembly kinetics of recombinant Aβ(1-42) into amyloid fibrils in vitro. Cu²⁺ inhibits both the unseeded and seeded aggregation of Aβ(1-42) at pH 8.0. Using mathematical models to fit the kinetic data, we find that Cu²⁺ prevents fibril elongation. The Cu²⁺-mediated inhibition of Aβ aggregation shows the largest effect around pH 6.0 but is lost at pH 5.0, which corresponds to the pH in lysosomes. In contrast to Cu²⁺, Cu⁺ ion binding mildly catalyzes the Aβ(1-42) aggregation via a mechanism that accelerates primary nucleation, possibly via the formation of Cu⁺-bridged Aβ(1-42) dimers. Taken together, our study emphasizes redox-dependent copper ion effects on Aβ(1-42) aggregation and thereby provides further knowledge of putative copper-dependent mechanisms resulting in AD. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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19 pages, 499 KiB

Open AccessArticle

Cigarette Smoking during Pregnancy: Effects on Antioxidant Enzymes, Metallothionein and Trace Elements in Mother-Newborn Pairs

by Alica Pizent, Maja Lazarus, Jelena Kovačić, Blanka Tariba Lovaković, Irena Brčić Karačonji, Tanja Živković Semren, Ankica Sekovanić, Tatjana Orct, Karmen Branović-Čakanić, Nataša Brajenović, Andreja Jurič, Iva Miškulin, Lana Škrgatić, Sandra Stasenko, Tatjana Mioč, Jasna Jurasović and Martina Piasek

Biomolecules 2020, 10(6), 892; https://doi.org/10.3390/biom10060892 - 10 Jun 2020

Cited by 14 | Viewed by 3385

Abstract

The effect of maternal smoking as a source of exposure to toxic metals Cd and Pb on superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity, metallothionein (MT), Cd, Pb, Cu, Fe, Mn, Se and Zn concentrations were assessed in maternal and umbilical cord blood and placenta in 74 healthy mother-newborn pairs after term delivery. Sparse discriminant analysis (SDA) was used to identify elements with the strongest impact on the SOD, GPx and MT in the measured compartments, which was then quantified by multiple regression analysis. SOD activity was lower in maternal and cord plasma, and higher in the placenta of smokers compared to non-smokers, whereas GPx activity and MT concentration did not differ between the groups. Although active smoking during pregnancy contributed to higher maternal Cd and Pb concentrations, its contribution to the variability of SOD, GPx or MT after control for other elements identified by SDA was not significant. However, an impaired balance in the antioxidant defence observed in the conditions of relatively low-to-moderate exposure levels to Cd and Pb could contribute to an increased susceptibility of offspring to oxidative stress and risk of disease development later in life. Further study on a larger number of subjects will help to better understand complex interactions between exposure to toxic elements and oxidative stress related to maternal cigarette smoking. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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28 pages, 2215 KiB

Open AccessArticle

Mercury Exposure Assessment in Mother–Infant Pairs from Continental and Coastal Croatia

by Ankica Sekovanić, Martina Piasek, Tatjana Orct, Antonija Sulimanec Grgec, Marijana Matek Sarić, Sandra Stasenko and Jasna Jurasović

Biomolecules 2020, 10(6), 821; https://doi.org/10.3390/biom10060821 - 27 May 2020

Cited by 12 | Viewed by 3320

Abstract

The main source of mercury (Hg) exposure in the general population is fish. Another possible source is dental amalgam. Here, we compare the levels of Hg and selenium (Se) in samples of maternal and fetal origin collected shortly after childbirth of healthy postpartum women in the coastal (n = 96) and continental (n = 185) areas of Croatia related to maternal seafood/fish consumption. We also evaluated Hg concentrations and maternal serum metallothionein (MT2) concentrations in relation to the number of dental amalgam fillings, and MT2A-5A/G (rs28366003) polymorphism. The levels of Hg and Se in maternal hair and blood/serum, placenta and cord blood/serum increased in relation to increasing fish consumption with the highest values in subjects from the coast. The concentrations of each element and between elements correlated across the matrices. Increasing amalgam number correlated linearly with increased Hg levels in maternal and cord serum and was not associated with serum MT2. No association of MT2A-5A/G polymorphism and Hg or Se levels were found. The results confirmed higher fish consumption in coastal vs. continental Croatia and increases of both Hg and Se related to fish consumption in all analyzed samples. Increased blood Hg reflected the predominant MeHg share from seafood, while increased serum Hg matched exposure from dental amalgams. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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19 pages, 2678 KiB

Open AccessArticle

A Preliminary Study of Cu Exposure Effects upon Alzheimer’s Amyloid Pathology

by Alexander Pilozzi, Zhanyang Yu, Isabel Carreras, Kerry Cormier, Dean Hartley, Jack Rogers, Alpaslan Dedeoglu and Xudong Huang

Biomolecules 2020, 10(3), 408; https://doi.org/10.3390/biom10030408 - 6 Mar 2020

Cited by 5 | Viewed by 3335

Abstract

A large body of evidence indicates that dysregulation of cerebral biometals (Fe, Cu, Zn) and their interactions with amyloid precursor protein (APP) and Aβ amyloid may contribute to the Alzheimer’s disease (AD) Aβ amyloid pathology. However, the molecular underpinnings associated with the interactions are still not fully understood. Herein we have further validated the exacerbation of Aβ oligomerization by Cu and H₂O₂ in vitro. We have also reported that Cu enhanced APP translations via its 5′ untranslated region (5′UTR) of mRNA in SH-SY5Y cells, and increased Aβ amyloidosis and expression of associated pro-inflammatory cytokines such as MCP-5 in Alzheimer’s APP/PS1 doubly transgenic mice. This preliminary study may further unravel the pathogenic role of Cu in Alzheimer’s Aβ amyloid pathogenesis, warranting further investigation. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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8 pages, 1683 KiB

Open AccessArticle

The Reliability of Iodine Concentration in Diaper-Retrieved Infant Urine Using Urine Collection Pads, and in Their Mothers’ Breastmilk

by Kjersti Sletten Bakken, Ingvild Oma, Synne Groufh-Jacobsen, Beate Stokke Solvik, Lise Mette Mosand, Mina Marthinsen Langfjord, Elin Lovise Folven Gjengedal, Sigrun Henjum and Tor Arne Strand

Biomolecules 2020, 10(2), 295; https://doi.org/10.3390/biom10020295 - 13 Feb 2020

Cited by 4 | Viewed by 4080

Abstract

Mild to moderate iodine deficiency is common among women of childbearing age. Data on iodine status in infants are sparse, partly due to the challenges in collecting urine. Urinary iodine concentration (UIC) is considered a good marker for recent dietary iodine intake and status in populations. The aim of this study was to investigate the reliability of iodine concentration measured in two spot-samples from the same day of diaper-retrieved infant urine and in their mothers’ breastmilk. We collected urine and breastmilk from a sample of 27 infants and 25 mothers participating in a cross-sectional study at two public healthcare clinics in Norway. The reliability of iodine concentration was assessed by calculating the intraclass correlation coefficients (ICC) and the coefficient of variation (CV). The ICC for infants’ urine was 0.64 (95% confidence interval (CI) 0.36–0.82), while the ICC for breastmilk was 0.83 (95% CI 0.65–0.92) Similarly, the intraindividual CV for UIC was 0.25 and 0.14 for breastmilk iodine concentration (BIC). Compared to standard methods of collecting urine for measuring iodine concentration, the diaper-pad collection method does not substantially affect the reliability of the measurements. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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23 pages, 2912 KiB

Open AccessArticle

Mercury and Alzheimer’s Disease: Hg(II) Ions Display Specific Binding to the Amyloid-β Peptide and Hinder Its Fibrillization

by Cecilia Wallin, Merlin Friedemann, Sabrina B. Sholts, Andra Noormägi, Teodor Svantesson, Jüri Jarvet, Per M. Roos, Peep Palumaa, Astrid Gräslund and Sebastian K. T. S. Wärmländer

Biomolecules 2020, 10(1), 44; https://doi.org/10.3390/biom10010044 - 27 Dec 2019

Cited by 27 | Viewed by 5665

Abstract

Brains and blood of Alzheimer’s disease (AD) patients have shown elevated mercury concentrations, but potential involvement of mercury exposure in AD pathogenesis has not been studied at the molecular level. The pathological hallmark of AD brains is deposition of amyloid plaques, consisting mainly of amyloid-β (Aβ) peptides aggregated into amyloid fibrils. Aβ peptide fibrillization is known to be modulated by metal ions such as Cu(II) and Zn(II). Here, we study in vitro the interactions between Aβ peptides and Hg(II) ions by multiple biophysical techniques. Fluorescence spectroscopy and atomic force microscopy (AFM) show that Hg(II) ions have a concentration-dependent inhibiting effect on Aβ fibrillization: at a 1:1 Aβ·Hg(II) ratio only non-fibrillar Aβ aggregates are formed. NMR spectroscopy shows that Hg(II) ions interact with the N-terminal region of Aβ(1–40) with a micromolar affinity, likely via a binding mode similar to that for Cu(II) and Zn(II) ions, i.e., mainly via the histidine residues His6, His13, and His14. Thus, together with Cu(II), Fe(II), Mn(II), Pb(IV), and Zn(II) ions, Hg(II) belongs to a family of metal ions that display residue-specific binding interactions with Aβ peptides and modulate their aggregation processes. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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20 pages, 1189 KiB

Open AccessFeature PaperArticle

Significant Changes in Metabolic Profiles after Intervention with Selenium and Coenzyme Q10 in an Elderly Population

by Urban Alehagen, Peter Johansson, Jan Aaseth, Jan Alexander, Izabella Surowiec, Katrin Lundstedt-Enkel and Torbjörn Lundstedt

Biomolecules 2019, 9(10), 553; https://doi.org/10.3390/biom9100553 - 30 Sep 2019

Cited by 14 | Viewed by 3433

Abstract

Selenium and coenzyme Q₁₀ (SeQ₁₀) are important for normal cellular function. Low selenium intake leads to increased cardiovascular mortality. Intervention with these substances with healthy elderly persons over a period of four years in a double-blind, randomised placebo-controlled prospective study showed reduced cardiovascular mortality, increased cardiac function, and a lower level of NT-proBNP. Therefore, we wanted to evaluate changes in biochemical pathways as a result of the intervention with SeQ₁₀ using metabolic profiling. From a population of 443 healthy elderly individuals that were given 200 µg selenium and 200 mg coenzyme Q₁₀, or placebo daily for four years, we selected nine males on active intervention and nine males on placebo for metabolic profiling in the main study. To confirm the results, two validation studies (study 1 n = 60 males, study 2 n = 37 males) were conducted. Principal component analyses were used on clinical and demographic data to select representative sets of samples for analysis and to divide the samples into batches for analysis. Gas chromatography time-of-flight mass spectrometry-based metabolomics was applied. The metabolite data were evaluated using univariate and multivariate approaches, mainly T-tests and orthogonal projections to latent structures (OPLS) analyses. Out of 95 identified metabolites, 19 were significantly decreased due to the intervention after 18 months of intervention. Significant changes could be seen in the pentose phosphate, the mevalonate, the beta-oxidation and the xanthine oxidase pathways. The intervention also resulted in changes in the urea cycle, and increases in the levels of the precursors to neurotransmitters of the brain. This adds information to previous published results reporting decreased oxidative stress and inflammation. This is the first-time metabolic profiling has been applied to elucidate the mechanisms behind an intervention with SeQ₁₀. The study is small and should be regarded as hypothesis-generating; however, the results are interesting and, therefore, further research in the area is needed. This study was registered at Clinicaltrials.gov, with the identifier NCT01443780. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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Review

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29 pages, 2170 KiB

Open AccessReview

General Aspects of Metal Ions as Signaling Agents in Health and Disease

by Karolina Krzywoszyńska, Danuta Witkowska, Jolanta Świątek-Kozłowska, Agnieszka Szebesczyk and Henryk Kozłowski

Biomolecules 2020, 10(10), 1417; https://doi.org/10.3390/biom10101417 - 7 Oct 2020

Cited by 31 | Viewed by 4038

Abstract

This review focuses on the current knowledge on the involvement of metal ions in signaling processes within the cell, in both physiological and pathological conditions. The first section is devoted to the recent discoveries on magnesium and calcium-dependent signal transduction—the most recognized signaling agents among metals. The following sections then describe signaling pathways where zinc, copper, and iron play a key role. There are many systems in which changes in intra- and extra-cellular zinc and copper concentrations have been linked to important downstream events, especially in nervous signal transduction. Iron signaling is mostly related with its homeostasis. However, it is also involved in a recently discovered type of programmed cell death, ferroptosis. The important differences in metal ion signaling, and its disease-leading alterations, are also discussed. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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19 pages, 780 KiB

Open AccessReview

Agricultural Use of Copper and Its Link to Alzheimer’s Disease

by Fábio C. Coelho, Rosanna Squitti, Mariacarla Ventriglia, Giselle Cerchiaro, João P. Daher, Jaídson G. Rocha, Mauro C. A. Rongioletti and Anna-Camilla Moonen

Biomolecules 2020, 10(6), 897; https://doi.org/10.3390/biom10060897 - 12 Jun 2020

Cited by 36 | Viewed by 4862

Abstract

Copper is an essential nutrient for plants, animals, and humans because it is an indispensable component of several essential proteins and either lack or excess are harmful to human health. Recent studies revealed that the breakdown of the regulation of copper homeostasis could be associated with Alzheimer’s disease (AD), the most common form of dementia. Copper accumulation occurs in human aging and is thought to increase the risk of AD for individuals with a susceptibility to copper exposure. This review reports that one of the leading causes of copper accumulation in the environment and the human food chain is its use in agriculture as a plant protection product against numerous diseases, especially in organic production. In the past two decades, some countries and the EU have invested in research to reduce the reliance on copper. However, no single alternative able to replace copper has been identified. We suggest that agroecological approaches are urgently needed to design crop protection strategies based on the complementary actions of the wide variety of crop protection tools for disease control. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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31 pages, 1465 KiB

Open AccessReview

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity

by Alexey A. Tinkov, Olga P. Ajsuvakova, Tommaso Filippini, Ji-Chang Zhou, Xin Gen Lei, Eugenia R. Gatiatulina, Bernhard Michalke, Margarita G. Skalnaya, Marco Vinceti, Michael Aschner and Anatoly V. Skalny

Biomolecules 2020, 10(4), 658; https://doi.org/10.3390/biom10040658 - 24 Apr 2020

Cited by 68 | Viewed by 7847

Abstract

Selenium (Se) homeostasis is tightly related to carbohydrate and lipid metabolism, but its possible roles in obesity development and in adipocyte metabolism are unclear. The objective of the present study is to review the current data on Se status in obesity and to discuss the interference between Se and selenoprotein metabolism in adipocyte physiology and obesity pathogenesis. The overview and meta-analysis of the studies on blood Se and selenoprotein P (SELENOP) levels, as well as glutathione peroxidase (GPX) activity in obese subjects, have yielded heterogenous and even conflicting results. Laboratory studies demonstrate that Se may modulate preadipocyte proliferation and adipogenic differentiation, and also interfere with insulin signaling, and regulate lipolysis. Knockout models have demonstrated that the selenoprotein machinery, including endoplasmic reticulum-resident selenoproteins together with GPXs and thioredoxin reductases (TXNRDs), are tightly related to adipocyte development and functioning. In conclusion, Se and selenoproteins appear to play an essential role in adipose tissue physiology, although human data are inconsistent. Taken together, these findings do not support the utility of Se supplementation to prevent or alleviate obesity in humans. Further human and laboratory studies are required to elucidate associations between Se metabolism and obesity. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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16 pages, 1717 KiB

Open AccessReview

Arsenic Toxicity: Molecular Targets and Therapeutic Agents

by Valeria M. Nurchi, Aleksandra Buha Djordjevic, Guido Crisponi, Jan Alexander, Geir Bjørklund and Jan Aaseth

Biomolecules 2020, 10(2), 235; https://doi.org/10.3390/biom10020235 - 4 Feb 2020

Cited by 152 | Viewed by 9636

Abstract

High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As²⁺ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As²⁺-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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10 pages, 697 KiB

Open AccessReview

Medical Therapy of Patients Contaminated with Radioactive Cesium or Iodine

by Jan Aaseth, Valeria Marina Nurchi and Ole Andersen

Biomolecules 2019, 9(12), 856; https://doi.org/10.3390/biom9120856 - 11 Dec 2019

Cited by 23 | Viewed by 5588

Abstract

Follow-up studies after the Chernobyl and Fukushima accidents have shown that ¹³⁷Cs and ¹³¹I made up the major amount of harmful contaminants in the atmospheric dispersion and fallout. Other potential sources for such radionuclide exposure may be terrorist attacks, e.g., via contamination of drinking water reservoirs. A primary purpose of radionuclide mobilization is to minimize the radiation dose. Rapid initiation of treatment of poisoned patients is imperative after a contaminating event. Internal contamination with radioactive material can expose patients to prolonged radiation, thus leading to short- and long-term clinical consequences. After the patient’s emergency conditions are addressed, the treating physicians and assisting experts should assess the amount of radioactive material that has been internalized. This evaluation should include estimation of the radiation dose that is delivered and the specific radionuclides inside the body. These complex assessments warrant the reliance on a multidisciplinary approach that incorporates regional experts in radiation medicine and emergencies. Regional hospitals should have elaborated strategies for the handling of radiation emergencies. If radioactive cesium is a significant pollutant, Prussian blue is the approved antidote for internal detoxification. Upon risks of radioiodine exposure, prophylactic or immediate treatment with potassium iodide tablets is recommended. Chelators developed from calcium salts have been studied for gastrointestinal trapping and enhanced mobilization after strontium exposure. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease)

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