Biomolecules

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5 pages, 195 KiB

Open AccessEditorial

Toxic and Essential Metals in Human Health and Disease 2021

by Jan O. Aaseth

Biomolecules 2022, 12(10), 1375; https://doi.org/10.3390/biom12101375 - 26 Sep 2022

Cited by 2 | Viewed by 1747

Abstract

The Special Issue of Biomolecules called “Toxic and Essential Metals in Human Health and Disease 2021” represents a follow-up of the previous Special Issue with the name of “Toxic and Essential Metals in Human Health and Disease” [...] Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

Research

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16 pages, 4131 KiB

Open AccessArticle

Zn²⁺ and Cu²⁺ Binding to the Extramembrane Loop of Zrt2, a Zinc Transporter of Candida albicans

by Denise Bellotti, Adriana Miller, Magdalena Rowińska-Żyrek and Maurizio Remelli

Biomolecules 2022, 12(1), 121; https://doi.org/10.3390/biom12010121 - 12 Jan 2022

Cited by 10 | Viewed by 2588

Abstract

Zrt2 is a zinc transporter of the ZIP family. It is predicted to be located in the plasma membrane and it is essential for Candida albicans zinc uptake and growth at acidic pH. Zrt2 from C. albicans is composed of 370 amino acids [...] Read more.

Zrt2 is a zinc transporter of the ZIP family. It is predicted to be located in the plasma membrane and it is essential for Candida albicans zinc uptake and growth at acidic pH. Zrt2 from C. albicans is composed of 370 amino acids and contains eight putative transmembrane domains and an extra-membrane disordered loop, corresponding to the amino acid sequence 126–215. This protein region contains at least three possible metal binding motifs: HxHxHxxD (144–153), HxxHxxEHxD (181–193) and the Glu- and Asp- rich sequence DDEEEDxE (161–168). The corresponding model peptides, protected at their termini (Ac-GPHTHSHFGD-NH₂, Ac-DDEEEDLE-NH₂ and Ac-PSHFAHAQEHQDP-NH₂), have been investigated in order to elucidate the thermodynamic and coordination properties of their Zn²⁺ and Cu²⁺ complexes, with the further aim to identify the most effective metal binding site among the three fragments. Furthermore, we extended the investigation to the peptides Ac-GPHTHAHFGD-NH₂ and Ac-PAHFAHAQEHQDP-NH₂, where serine residues have been substituted by alanines in order to check if the presence of a serine residue may favor the displacement of amidic protons by Cu²⁺. In the native Zrt2 protein, the Ac-GPHTHSHFGD-NH₂ region of the Zrt2 loop has the highest metal binding affinity, showing that three alternated histidines separated by only one residue (-HxHxH-) bind Zn²⁺ and Cu²⁺ more strongly than the region in which three histidines are separated by two and three His residues (-HxxHxxxH- in Ac-PSHFAHAQEHQDP-NH₂). All studied Zrt2 loop fragments have lower affinity towards Zn²⁺ than the zinc(II) binding site on the Zrt1 transporter; also, all three Zrt2 regions bind Zn²⁺ and Cu²⁺ with comparable affinity below pH 5 and, therefore, may equally contribute to the metal acquisition under the most acidic conditions in which the Zrt2 transporter is expressed. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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20 pages, 17175 KiB

Open AccessArticle

The Labile Iron Pool Reacts Rapidly and Catalytically with Peroxynitrite

by André Luís Condeles and José Carlos Toledo Junior

Biomolecules 2021, 11(9), 1331; https://doi.org/10.3390/biom11091331 - 9 Sep 2021

Cited by 8 | Viewed by 2819

Abstract

While investigating peroxynitrite-dependent oxidation in murine RAW 264.7 macrophage cells, we observed that removal of the Labile Iron Pool (LIP) by chelation increases the intracellular oxidation of the fluorescent indicator H₂DCF, so we concluded that the LIP reacts with peroxynitrite and [...] Read more.

While investigating peroxynitrite-dependent oxidation in murine RAW 264.7 macrophage cells, we observed that removal of the Labile Iron Pool (LIP) by chelation increases the intracellular oxidation of the fluorescent indicator H₂DCF, so we concluded that the LIP reacts with peroxynitrite and decreases the yield of peroxynitrite-derived oxidants. This was a paradigm-shifting finding in LIP biochemistry and raised many questions. In this follow-up study, we address fundamental properties of the interaction between the LIP and peroxynitrite by using the same cellular model and fluorescence methodology. We have identified that the reaction between the LIP and peroxynitrite has catalytic characteristics, and we have estimated that the rate constant of the reaction is in the range of 10⁶ to 10⁷ M⁻¹s⁻¹. Together, these observations suggest that the LIP represents a constitutive peroxynitrite reductase system in RAW 264.7 cells. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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24 pages, 2989 KiB

Open AccessEditor’s ChoiceArticle

Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance

by Sherleen Xue-Fu Adamson, Wei Zheng, Zeynep Sena Agim, Sarah Du, Sheila Fleming, Jonathan Shannahan and Jason Cannon

Biomolecules 2021, 11(9), 1315; https://doi.org/10.3390/biom11091315 - 6 Sep 2021

Cited by 6 | Viewed by 3511

Abstract

Disrupted systemic copper (Cu) homeostasis underlies neurodegenerative diseases with early symptoms including olfactory dysfunction. This study investigated the impact of Cu dyshomeostasis on olfactory function, adult neurogenesis, and neurochemical balance. Models of Cu deficiency (CuD) and Cu overload (CuO) were established by feeding [...] Read more.

Disrupted systemic copper (Cu) homeostasis underlies neurodegenerative diseases with early symptoms including olfactory dysfunction. This study investigated the impact of Cu dyshomeostasis on olfactory function, adult neurogenesis, and neurochemical balance. Models of Cu deficiency (CuD) and Cu overload (CuO) were established by feeding adult rats with Cu-restricted diets plus ip. injection of a Cu chelator (ammonium tetrathiomolybdate) and excess Cu, respectively. CuD reduced Cu levels in the olfactory bulb (OB), subventricular zone (SVZ), rostral migratory stream (RMS), and striatum, while CuO increased Cu levels in these areas. The buried pellet test revealed both CuD and CuO prolonged the latency to uncover food. CuD increased neural proliferation and stem cells in the SVZ and newly differentiated neurons in the OB, whereas CuO caused opposite alterations, suggesting a “switch”-type function of Cu in regulating adult neurogenesis. CuO increased GABA in the OB, while both CuD and CuO reduced DOPAC, HVA, 5-HT and the DA turnover rate in olfactory-associated brain regions. Altered mRNA expression of Cu transport and storage proteins in tested brain areas were observed under both conditions. Together, results support an association between systemic Cu dyshomeostasis and olfactory dysfunction. Specifically, altered adult neurogenesis along the SVZ-RMS-OB pathway and neurochemical imbalance could be the factors that may contribute to olfactory dysfunction. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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28 pages, 7018 KiB

Open AccessArticle

The Solution Behavior of Dopamine in the Presence of Mono and Divalent Cations: A Thermodynamic Investigation in Different Experimental Conditions

by Antonio Gigliuto, Rosalia Maria Cigala, Anna Irto, Maria Rosa Felice, Alberto Pettignano, Demetrio Milea, Stefano Materazzi, Concetta De Stefano and Francesco Crea

Biomolecules 2021, 11(9), 1312; https://doi.org/10.3390/biom11091312 - 5 Sep 2021

Cited by 6 | Viewed by 2371

Abstract

The interactions of dopamine [2-(3,4-Dihydroxyphenyl)ethylamine, (Dop⁻)] with methylmercury(II) (CH₃Hg⁺), magnesium(II), calcium(II), and tin(II) were studied in NaCl(aq) at different ionic strengths and temperatures. Different speciation models were obtained, mainly characterized by mononuclear species. Only for Sn²⁺ [...] Read more.

The interactions of dopamine [2-(3,4-Dihydroxyphenyl)ethylamine, (Dop⁻)] with methylmercury(II) (CH₃Hg⁺), magnesium(II), calcium(II), and tin(II) were studied in NaCl(aq) at different ionic strengths and temperatures. Different speciation models were obtained, mainly characterized by mononuclear species. Only for Sn²⁺ we observed the formation of binuclear complexes (M₂L₂ and M₂LOH (charge omitted for simplicity); M = Sn²⁺, L = Dop⁻). For CH₃Hg⁺, the speciation model reported the ternary MLCl (M = CH₃Hg⁺) complex. The dependence on the ionic strength of complex formation constants was modeled by using both an extended Debye–Hückel equation that included the Van’t Hoff term for the calculation of enthalpy change values of the formation and the Specific Ion Interaction Theory (SIT). The results highlighted that, in general, the entropy is the driving force of the process. The sequestering ability of dopamine towards the investigated cations was evaluated using the calculation of pL_0.5 parameter. The sequestering ability trend resulted to be: Sn²⁺ > CH₃Hg⁺ > Ca²⁺ > Mg²⁺. For example, at I = 0.15 mol dm⁻³, T = 298.15 K and pH = 7.4, pL_0.5 = 3.46, 2.63, 1.15, and 2.27 for Sn²⁺, CH₃Hg⁺, Ca²⁺ and Mg²⁺ (pH = 9.5 for Mg²⁺), respectively. For the Ca²⁺/Dop⁻ system, the precipitates collected at the end of the potentiometric titrations were analyzed by thermogravimetry (TGA). The thermogravimetric calculations highlighted the formation of solid with stoichiometry dependent on the different metal:ligand ratios and concentrations of the starting solutions. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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21 pages, 5479 KiB

Open AccessArticle

The Study of the Aorta Metallomics in the Context of Atherosclerosis

by Aleksandra Kuzan, Marta Wujczyk and Rafal J. Wiglusz

Biomolecules 2021, 11(7), 946; https://doi.org/10.3390/biom11070946 - 25 Jun 2021

Cited by 7 | Viewed by 2637

Abstract

Atherosclerosis is a multifactorial disease, for which the etiology is so complex that we are currently unable to prevent it and effectively lower the statistics on mortality from cardiovascular diseases. Parallel to modern analyses in molecular biology and biochemistry, we want to carry [...] Read more.

Atherosclerosis is a multifactorial disease, for which the etiology is so complex that we are currently unable to prevent it and effectively lower the statistics on mortality from cardiovascular diseases. Parallel to modern analyses in molecular biology and biochemistry, we want to carry out analyses at the level of micro- and macroelements in order to discover the interdependencies between elements during atherogenesis. In this work, we used the Inductively Coupled Plasma Optical Emission Spectrometer (ICP-OES) to determine the content of calcium, magnesium, iron, copper, chromium, zinc, manganese, cadmium, lead, and zinc in the aorta sections of people who died a sudden death. We also estimated the content of metalloenzymes MMP-9, NOS-3, and SOD-2 using the immunohistochemical method. It was observed that with the age of the patient, the calcium content of the artery increased, while the content of copper and iron decreased. Very high correlations (correlation coefficient above 0.8) were observed for pairs of parameters in women: Mn–Ca, Fe–Cu, and Ca–Cd, and in men: Mn–Zn. The degree of atherosclerosis negatively correlated with magnesium and with cadmium. Chromium inhibited absorption of essential trace elements such as Cu and Fe due to its content being above the quantification threshold only if Cu and Fe were lower. Moreover, we discussed how to design research for the future in order to learn more about the pathomechanism of atherosclerosis and the effect of taking dietary supplements on the prevalence of cardiovascular diseases. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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12 pages, 481 KiB

Open AccessFeature PaperArticle

Trace Element and Mineral Levels in Serum, Hair, and Urine of Obese Women in Relation to Body Composition, Blood Pressure, Lipid Profile, and Insulin Resistance

by Alexey A. Tinkov, Paweł Bogdański, Damian Skrypnik, Katarzyna Skrypnik, Anatoly V. Skalny, Jan Aaseth, Margarita G. Skalnaya and Joanna Suliburska

Biomolecules 2021, 11(5), 689; https://doi.org/10.3390/biom11050689 - 4 May 2021

Cited by 27 | Viewed by 3744

Abstract

The objective of this study was to evaluate serum, hair, and urinary trace element and mineral content in normal-weight and obese women in relation to metabolic risk factors. A total of 80 women aged 30–70 y.o. were enrolled in the obese group (n [...] Read more.

The objective of this study was to evaluate serum, hair, and urinary trace element and mineral content in normal-weight and obese women in relation to metabolic risk factors. A total of 80 women aged 30–70 y.o. were enrolled in the obese group (n = 40) and normal-weight group (n = 40). Serum, hair, and urinary trace element and mineral levels were assessed using inductively coupled plasma spectrometry. Body fat percentage was evaluated using bioimpedance. Obese subjects were characterized by significantly higher body fat percentage, blood pressure, serum triglyceride concentration, and insulin resistance. Serum Ca, Fe, Mg, Se, V, Zn levels, hair Fe, Mg, V content, and urinary Se and V concentrations were found to be lower in obese subjects as compared to lean controls. In turn, serum Cu and urinary Fe levels in obese women were characterized by a significant increase. In multiple regression models serum Cu, Se, and Zn levels were significantly associated with BMI even after adjustment for blood biochemistry, body composition, and blood pressure. Serum trace element and mineral levels also significantly contributed to group discrimination. These findings allow to propose that obesity-associated disturbances in trace element and mineral status may at least partially contribute to metabolic risk in obese subjects. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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16 pages, 1850 KiB

Open AccessArticle

Concentrations of Ca, Mg, P, Prostaglandin E2 in Bones and Parathyroid Hormone; 1,25-dihydroxyvitamin D3; 17-β-estradiol; Testosterone and Somatotropin in Plasma of Aging Rats Subjected to Physical Training in Cold Water

by Mateusz Bosiacki, Izabela Gutowska, Katarzyna Piotrowska and Anna Lubkowska

Biomolecules 2021, 11(5), 616; https://doi.org/10.3390/biom11050616 - 21 Apr 2021

Cited by 5 | Viewed by 2816

Abstract

Exposure to low temperatures can be considered a stressor, which when applied for a specific time can lead to adaptive reactions. In our study we hypothesized that cold, when applied to the entire body, may be a factor that positively modifies the aging [...] Read more.

Exposure to low temperatures can be considered a stressor, which when applied for a specific time can lead to adaptive reactions. In our study we hypothesized that cold, when applied to the entire body, may be a factor that positively modifies the aging process of bones by improving the mechanisms related to the body’s mineral balance. Taking the above into account, the aim of the study was to determine the concentration of calcium (Ca), magnesium (Mg), and phosphorus (P) in bones, and to examine bone density and concentrations of the key hormones for bone metabolism, namely parathyroid hormone (PTH), somatotropin (GH), 1,25-dihydroxyvitamin D3, 17-β estradiol, testosterone (T) in plasma, and prostaglandin E2 (PGE2) in the bone of aging rats subjected to physical training in cold water. The animals in the experiment were subjected to a series of swimming sessions for nine weeks. Study group animals (male and female respectively) performed swimming training in cold water at 5 ± 2 °C and in water with thermal comfort temperature (36 ± 2 °C). Control animals were kept in a sedentary condition. Immersion in cold water affects bone mineral metabolism in aging rats by changing the concentration of Ca, Mg, and P in the bone, altering bone mineral density and the concentration of key hormones involved in the regulation of bone mineral metabolism. The effect of cold-water immersion may be gender-dependent. In females, it decreases Ca and Mg content in bones while increasing bone density and 17-β estradiol and 1,25-dihydroxyvitamin D3 levels, and with a longer perspective in aging animals may be positive not only for bone health but also other estrogen-dependent tissues. In males, cold water swimming decreased PTH and PGE2 which resulted in a decrease in phosphorus content in bones (with no effect on bone density), an increase in 1,25-dihydroxyvitamin D3, and increase in T and GH, and may have positive consequences especially in bones and muscle tissue for the prevention of elderly sarcopenia. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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10 pages, 473 KiB

Open AccessArticle

Iron Status of Vegans, Vegetarians and Pescatarians in Norway

by Sigrun Henjum, Synne Groufh-Jacobsen, Tonje Holte Stea, Live Edvardsen Tonheim and Kari Almendingen

Biomolecules 2021, 11(3), 454; https://doi.org/10.3390/biom11030454 - 18 Mar 2021

Cited by 11 | Viewed by 12606

Abstract

Although plant-based diets provide well-established physical and environmental health benefits, omitting meat or meat products has also been associated with a risk of being deficient in specific nutrients, such as iron. As data on the iron status among Norwegian vegans, vegetarians and pescatarians [...] Read more.

Although plant-based diets provide well-established physical and environmental health benefits, omitting meat or meat products has also been associated with a risk of being deficient in specific nutrients, such as iron. As data on the iron status among Norwegian vegans, vegetarians and pescatarians are lacking, the present study aimed to assess iron status in these groups of healthy adults. Blood markers for iron status were measured in 191 participants (18–60 years old) comprising 106 vegans, 54 vegetarians and 31 pescatarians: serum-ferritin (S-Fe), serum-iron (S-Iron) and serum-total iron binding capacity (S-TIBC). Serum-transferrin-saturation (S-TSAT) was estimated (S-Iron/S-TIBC × 100). The median concentration of blood markers for iron status were within the normal range with no difference between the different dietary practices. In total, 9% reported iron supplement use the last 24 h. S-Fe concentrations below reference (<15 μg/L) were found in 8% of the participating women, of which one participant reported iron supplement use. In multiple regression analysis, duration of adherence to dietary practices and the female gender were found to be the strongest predictors for decreased S-Fe concentration. In conclusion, although the participants were eating a plant-based diet, the majority had sufficient iron status. Female vegans and vegetarians of reproductive age are at risk of low iron status and should have their iron status monitored. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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22 pages, 4737 KiB

Open AccessArticle

Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer’s Disease Agents

by Viviana Poliseno, Sílvia Chaves, Leonardo Brunetti, Fulvio Loiodice, Antonio Carrieri, Antonio Laghezza, Paolo Tortorella, João D. Magalhães, Sandra M. Cardoso, M. Amélia Santos and Luca Piemontese

Biomolecules 2021, 11(1), 111; https://doi.org/10.3390/biom11010111 - 15 Jan 2021

Cited by 20 | Viewed by 3813

Abstract

Alzheimer’s disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as [...] Read more.

Alzheimer’s disease (AD) is generally recognized as a multifactorial neurodegenerative pathology with an increasing impact on society. Tenuazonic acid (TA) is a natural compound that was recently identified as a potential multitarget ligand with anti-cholinesterase, anti-amyloidogenic and antioxidant activities. Using its structure as a chemical scaffold, we synthesized and evaluated new derivatives (1–5), including tenuazonic-donepezil (TA-DNP) hybrids (4 and 5) due to the clinical importance of the anti-AD drug donepezil. These novel compounds all achieved activity in the micromolar range towards all selected targets and demonstrated to be potentially orally absorbed. Moreover, a selected compound (1) was further investigated as a chelating agent towards copper (II), zinc (II) and iron (III) and showed good chelating ability (pFe = 16.6, pCu = 11.6, pZn = 6.0 at pH 7.4). Therefore, the TA motif can be considered an interesting building block in the search for innovative multi-functional anti-neurodegenerative drugs, as exemplified by hybrid 5, a promising non-cytotoxic lead compound adequate for the early stages of AD, and capable of ameliorating the oxidative status of SH-SY5Y human neuroblastoma cells. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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11 pages, 1592 KiB

Open AccessFeature PaperArticle

Metallomics Analysis for Assessment of Toxic Metal Burdens in Infants/Children and Their Mothers: Early Assessment and Intervention Are Essential

by Hiroshi Yasuda, Toyoharu Tsutsui and Katsuhiko Suzuki

Biomolecules 2021, 11(1), 6; https://doi.org/10.3390/biom11010006 - 23 Dec 2020

Cited by 8 | Viewed by 4248

Abstract

Accumulation of toxic metals in infants/children is of serious concern worldwide, from the viewpoint of their harmful effects on the normal growth and development. This metallomics study investigates the extent of toxic metal burdens in infants/children and the relationship to those in their [...] Read more.

Accumulation of toxic metals in infants/children is of serious concern worldwide, from the viewpoint of their harmful effects on the normal growth and development. This metallomics study investigates the extent of toxic metal burdens in infants/children and the relationship to those in their mothers for 77 child/mother pair subjects. For mercury, its geometric mean concentration in infants/children was of similar level to that in their mothers, and a high-significant close correlation was observed between infants/children and their mothers (β = 0.758, r = 0.539, p < 0.0001). A significant but less intimate mother/child relationship was observed for arsenic (β = 0.301, r = 0.433), lead (β = 0.444, r = 0.471) and aluminum (β = 0.379, r = 0.451). Remarkably, the burden levels of lead, cadmium and aluminum in infants/children were approximately three times higher than those in their mothers (p < 0.0001), and the burden levels in some individuals were several tens of times higher than in the mothers. In contrast, some essential metal levels such as zinc, magnesium and calcium in infants/children were significantly lower than those in their mothers, and 29 individuals (37.7%) in the child subjects were estimated to be zinc-deficient. In addition, significant inverse correlations were observed between zinc and lead (r = −0.267, p = 0.019), and magnesium and arsenic (r = −0.514, p < 0.0001). These findings suggest that these toxic metal burdens and essential metal deficiencies in infants/children are of serious concern for their neurodevelopment, indicating that the early assessment and intervention are crucial. It is expected that larger epidemiological and intervention studies will provide a reasonable and essential pathway for intervention of neurodevelopment disorders. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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Review

Jump to: Editorial, Research

15 pages, 1350 KiB

Open AccessEditor’s ChoiceReview

Metallothionein and Cadmium Toxicology—Historical Review and Commentary

by Monica Nordberg and Gunnar F. Nordberg

Biomolecules 2022, 12(3), 360; https://doi.org/10.3390/biom12030360 - 24 Feb 2022

Cited by 97 | Viewed by 6743

Abstract

More than one and a half centuries ago, adverse human health effects were reported after use of a cadmium-containing silver polishing agent. Long-term cadmium exposure gives rise to kidney or bone disease, reproductive toxicity and cancer in animals and humans. At present, high [...] Read more.

More than one and a half centuries ago, adverse human health effects were reported after use of a cadmium-containing silver polishing agent. Long-term cadmium exposure gives rise to kidney or bone disease, reproductive toxicity and cancer in animals and humans. At present, high human exposures to cadmium occur in small-scale mining, underlining the need for preventive measures. This is particularly urgent in view of the growing demand for minerals and metals in global climate change mitigation. This review deals with a specific part of cadmium toxicology that is important for understanding when toxic effects appear and, thus, is crucial for risk assessment. The discovery of the low-molecular-weight protein metallothionein (MT) in 1957 was an important milestone because, when this protein binds cadmium, it modifies cellular cadmium toxicity. The present authors contributed evidence in the 1970s concerning cadmium binding to MT and synthesis of the protein in tissues. We showed that binding of cadmium to metallothionein in tissues prevented some toxic effects, but that metallothionein can increase the transport of cadmium to the kidneys. Special studies showed the importance of the Cd/Zn ratio in MT for expression of toxicity in the kidneys. We also developed models of cadmium toxicokinetics based on our MT-related findings. This model combined with estimates of tissue levels giving rise to toxicity, made it possible to calculate expected risks in relation to exposure. Other scientists developed these models further and international organizations have successfully used these amended models in recent publications. Our contributions in recent decades included studies in humans of MT-related biomarkers showing the importance of MT gene expression in lymphocytes and MT autoantibodies for risks of Cd-related adverse effects in cadmium-exposed population groups. In a study of the impact of zinc status on the risk of kidney dysfunction in a cadmium-exposed group, the risks were low when zinc status was good and high when zinc status was poor. The present review summarizes this evidence in a risk assessment context and calls for its application in order to improve preventive measures against adverse effects of cadmium exposures in humans and animals. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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17 pages, 1302 KiB

Open AccessReview

Selenium, TGF-Beta and Infectious Endemic Cardiopathy: Lessons from Benchwork to Clinical Application in Chagas Disease

by Tania C. Araujo-Jorge, Maria Teresa Rivera, Jean Vanderpas, Luciana R. Garzoni, Anna Cristina C. Carvalho, Mariana C. Waghabi, Marcelo T. Holanda, Mauro F. F. Mediano, Alejandro M. Hasslocher-Moreno, Maria da Gloria Bonecini-Almeida, Roberto M. Saraiva and Roberto R. Ferreira

Biomolecules 2022, 12(3), 349; https://doi.org/10.3390/biom12030349 - 23 Feb 2022

Cited by 5 | Viewed by 2813

Abstract

For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma [...] Read more.

For over 60 years, selenium (Se) has been known as an essential microelement to many biological functions, including cardiovascular homeostasis. This review presents a compilation of studies conducted in the past 20 years related to chronic Chagas disease cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, a neglected disease that represents a global burden, especially in Latin America. Experimental and clinical data indicate that Se may be used as a complementary therapy to prevent heart failure and improve heart function. Starting from the main questions “Is Se deficiency related to heart inflammation and arrhythmogenesis in CCC?” and “Could Se be recommended as a therapeutic strategy for CCC?”, we show evidence implicating the complex and multidetermined CCC physiopathology, discussing its possible interplays with the multifunctional cytokine TGF-β as regulators of immune response and fibrosis. We present two new proposals to face this global public health challenge in vulnerable populations affected by this parasitic disease: fibrosis modulation mediated by TGF-β pathways and the possible use of selenoproteins as antioxidants regulating the increased reactive oxygen stress present in CCC inflammatory environments. We assess the opportunity to consider the beneficial effects of Se in preventing heart failure as a concept to be applied for CCC patients. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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14 pages, 735 KiB

Open AccessReview

Impact of Selenium on Biomarkers and Clinical Aspects Related to Ageing. A Review

by Urban Alehagen, Trine B. Opstad, Jan Alexander, Anders Larsson and Jan Aaseth

Biomolecules 2021, 11(10), 1478; https://doi.org/10.3390/biom11101478 - 7 Oct 2021

Cited by 36 | Viewed by 6474

Abstract

Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1–3), glutathione peroxidases (GPX1–4 and GPX6) [...] Read more.

Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1–3), glutathione peroxidases (GPX1–4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1–4 and TXNRD1–3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress. In this review, we highlight the role of adequate Se status for human ageing and prevention of age-related diseases, and further its proposed role in preservation of telomere length in middle-aged and elderly individuals. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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12 pages, 588 KiB

Open AccessReview

Gut Microbiota as a Potential Player in Mn-Induced Neurotoxicity

by Alexey A. Tinkov, Airton C. Martins, Daiana Silva Avila, Victor A. Gritsenko, Anatoly V. Skalny, Abel Santamaria, Eunsook Lee, Aaron B. Bowman and Michael Aschner

Biomolecules 2021, 11(9), 1292; https://doi.org/10.3390/biom11091292 - 31 Aug 2021

Cited by 27 | Viewed by 4745

Abstract

Manganese (Mn) is an essential metal, which at high exposures causes neurotoxic effects and neurodegeneration. The neurotoxic effects of Mn are mediated by neuroinflammation, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, and other mechanisms. Recent findings have demonstrated the potential impact of Mn [...] Read more.

Manganese (Mn) is an essential metal, which at high exposures causes neurotoxic effects and neurodegeneration. The neurotoxic effects of Mn are mediated by neuroinflammation, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, and other mechanisms. Recent findings have demonstrated the potential impact of Mn overexposure on gut microbiota dysbiosis, which is known to contribute to neurodegeneration via secretion of neuroactive and proinflammatory metabolites. Therefore, in this review, we discuss the existing data on the impact of Mn exposure on gut microbiota biodiversity, bacterial metabolite production, and gut wall permeability regulating systemic levels. Recent data have demonstrated that Mn exposure may affect gut microbiota biodiversity by altering the abundance of Shiegella, Ruminococcus, Dorea, Fusicatenibacter, Roseburia, Parabacteroides, Bacteroidetes, Firmicutes, Ruminococcaceae, Streptococcaceae, and other bacterial phyla. A Mn-induced increase in Bacteroidetes abundance and a reduced Firmicutes/Bacteroidetes ratio may increase lipopolysaccharide levels. Moreover, in addition to increased systemic lipopolysaccharide (LPS) levels, Mn is capable of potentiating LPS neurotoxicity. Due to the high metabolic activity of intestinal microflora, Mn-induced perturbations in gut microbiota result in a significant alteration in the gut metabolome that has the potential to at least partially mediate the biological effects of Mn overexposure. At the same time, a recent study demonstrated that healthy microbiome transplantation alleviates Mn-induced neurotoxicity, which is indicative of the significant role of gut microflora in the cascade of Mn-mediated neurotoxicity. High doses of Mn may cause enterocyte toxicity and affect gut wall integrity through disruption of tight junctions. The resulting increase in gut wall permeability further promotes increased translocation of LPS and neuroactive bacterial metabolites to the systemic blood flow, ultimately gaining access to the brain and leading to neuroinflammation and neurotransmitter imbalance. Therefore, the existing data lead us to hypothesize that gut microbiota should be considered as a potential target of Mn toxicity, although more detailed studies are required to characterize the interplay between Mn exposure and the gut, as well as its role in the pathogenesis of neurodegeneration and other diseases. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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11 pages, 620 KiB

Open AccessReview

The Aging Kidney—As Influenced by Heavy Metal Exposure and Selenium Supplementation

by Jan Aaseth, Jan Alexander, Urban Alehagen, Alexey Tinkov, Anatoly Skalny, Anders Larsson, Guido Crisponi and Valeria Marina Nurchi

Biomolecules 2021, 11(8), 1078; https://doi.org/10.3390/biom11081078 - 22 Jul 2021

Cited by 30 | Viewed by 4199

Abstract

The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50–60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental [...] Read more.

The aging process in the kidneys has been well studied. It is known that the glomerular filtration rate (GFR) declines with age in subjects older than 50–60 years. However, there is still insufficient knowledge regarding the response of the aged kidney to environmental toxicants such as mercury, cadmium, and lead. Here, we present a review on the functional decline and proposed mechanisms in the aging kidney as influenced by metal pollutants. Due to the prevalence of these toxicants in the environment, human exposure is nearly unavoidable. Further, it is well known that acute and chronic exposures to toxic metals may be detrimental to kidneys of normal adults, thus it may be hypothesized that exposure of individuals with reduced GFR will result in additional reductions in renal function. Individuals with compromised renal function, either from aging or from a combination of aging and disease, may be particularly susceptible to environmental toxicants. The available data appear to show an association between exposure to mercury, cadmium and/or lead and an increase in incidence and severity of renal disease in elderly individuals. Furthermore, some physiological thiols, as well as adequate selenium status, appear to exert a protective action. Further studies providing improved insight into the mechanisms by which nephrotoxic metals are handled by aging kidneys, as well as possibilities of therapeutic protection, are of utmost importance. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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15 pages, 574 KiB

Open AccessFeature PaperReview

Iron Deficiency in Obesity and after Bariatric Surgery

by Geir Bjørklund, Massimiliano Peana, Lyudmila Pivina, Alexandru Dosa, Jan Aaseth, Yuliya Semenova, Salvatore Chirumbolo, Serenella Medici, Maryam Dadar and Daniel-Ovidiu Costea

Biomolecules 2021, 11(5), 613; https://doi.org/10.3390/biom11050613 - 21 Apr 2021

Cited by 36 | Viewed by 8874

Abstract

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, [...] Read more.

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, parallel to the increased concentrations of hepcidin. Obese subjects often get decreased inflammatory response after bariatric surgery, accompanied by decreased serum hepcidin and therefore improved iron absorption. Bariatric surgery can induce the mitigation or resolution of obesity-associated complications, such as hypertension, insulin resistance, diabetes mellitus, and hyperlipidemia, adjusting many parameters in the metabolism. However, gastric bypass surgery and sleeve gastrectomy can induce malabsorption and may accentuate ID. The present review explores the burden and characteristics of ID and anemia in obese patients after bariatric surgery, accounting for gastric bypass technique (Roux-en-Y gastric bypass—RYGB) and sleeve gastrectomy (SG). After bariatric surgery, obese subjects’ iron status should be monitored, and they should be motivated to use adequate and recommended iron supplementation. Full article

(This article belongs to the Special Issue Toxic and Essential Metals in Human Health and Disease 2021)

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