Alteration of iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) tissue levels and speciation in rats with desferioxamine-induced iron deficiency.

The objective of the present study was to investigate the impact of iron deficiency and iron replenishment on serum iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn) speciation and tissue accumulation in a deferrioxamine-induced model of iron deficiency. A total of 26 male Wistar rats were divided into three groups: control; Fe-deficient; Fe-replenished (with iron (II) gluconate). Serum ferritin and transferrin levels were assessed using immunoturbudimetric method. Liver, spleen, and serum metal levels were assessed using ICP-MS. Speciation analysis was performed using a hyphenated HPLC-ICP-MS technique. Desferrioxamine injections resulted in a significant decrease in tissue iron content that was reversed by Fe supplementation. Iron speciation revealed a significant increase in serum transferrin-bound iron and reduced ferritin-bound Fe levels. Serum but not tissue Cu levels were characterized by a significant decrease in hypoferremic rats, whereas ceruloplasmin-bound fraction tended to increase. At the same time, Zn levels were found to be higher in liver, spleen, and serum of Fe-deficient rats with a predominant increase in low molecular weight fraction.Both iron-deficient and iron-replenished rats were characteirzed by increased transferrin-bound Mn levels and reduced low-molecular weight fraction. Hypothetically, these differences may be associated with impaired Fe metabolism under Fe-deficient conditions predisposing to impairment of essential metal handling. However, further studies aimed at assessment of the impact on Fe deficiency on metal metabolism are highly required.

Profiling of selenium and other trace elements in breads from rice and maize cultivated in a seleniferous area of Punjab (India).

The objective of the study was to assess selenium and other elements levels in Indian Roti bread from Se-rich maize and rice using inductively coupled plasma mass-spectrometry. Se levels in Roti bread from Se-rich maize and rice exceeded those in the control samples by a factor of more than 594 and 156, respectively. Using Se-enriched maize increased bread Co, Cr, Mn, Mo, and Zn content, whereas Fe and I levels were reduced. In Se-rich rice-based bread a decrease in Co, Cr, Cu, Fe, I, Mo, and Zn contents was observed. Daily consumption of Se-rich maize and rice bread (100 g) could account for 5.665% and 4.309% from recommended dietary allowance, also exceeding the upper tolerable levels by a factor of 7.8 and 5.9, respectively. Therefore, Roti bread from both Se-rich maize and rice may be considered as an additional source of selenium. At the same time, regular intake of Se-rich grains and its products including breads may cause adverse health effects even after a few days and should be regularly monitored in order to prevent Se overload and toxicity.

Sulfhydryl groups as targets of mercury toxicity.

The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. In vivo, Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg2+, CH3Hg+, C2H5Hg+, C6H5Hg+) protein. At the Cys34 residue, Hg2+ binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys196), thioredoxin reductase (TrxR) (Cys497) activity, as well as limiting GSH (GS-HgCH3) and Trx (Cys32, 35, 62, 65, 73) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload.

Geographic variation of environmental, food, and human hair selenium content in an industrial region of Russia.

The objective of the present study was investigation of the selenium (Se) levels in environmental samples, main consumed food products, as well as human hair in the areas of the Orenburg region. Se levels in the environmental objects (water, soil, wheat), frequently consumed food products (wheat bread, ryebread, beef, pork, chicken, milk, cottage cheese), as well as human hair samples in the western (n = 210), central (n = 195), and eastern (n = 120) areas were assessed using inductively-coupled plasma mass-spectrometry and atomic absorption spectrometry (soil). The obtained data demonstrate that water (87% and 89%), soil (41% and 48%), and wheat (11% and 11%) Se levels Central and Eastern areas were significantly higher than those in the Western area. The level of Se in foods was found to be the highest in the Eastern (wheat bread and beef), Central and Eastern (ryebread and pork), or Central (milk and cottage cheese) areas of the Orenburg region. Hair Se content (0.298 (0.233-0.591) µg/g) as well as dietary Se intake (84.3 (73.7-95.8) µg/day) did not differ significantly between the studied areas. At the same time, regression analysis demonstrated that Se intake with wheat bread (ß = 0.634; p = 0.042) was the strongest predictor of hair Se. The revealed associations between environmental and food Se content and Se status of the population underline the necessity of continuous monitoring of Se intake and exposure in order to prevent potential health effects associated with both deficiency and overload.

Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta-analysis of epidemiologic studies.

Cadmium has been proposed to be the one of the factors of atherosclerosis development, although the existing data are still controversial. The primary objective of the present study is the review and the meta-analysis of studies demonstrating the association between Cd exposure and atherosclerosis as well as review of the potential mechanisms of such association. We performed a systematic search in the PubMed-Medline database using the MeSH terms cadmium, cardiovascular disease, atherosclerosis, coronary artery disease, myocardial infarction, stroke, mortality and humans up through December 20, 2017. Elevated urinary Cd levels were associated with increased mortality for cardiovascular disease (HR = 1.34, 95% CI: 1.07-1.67) as well as elevated blood Cd levels (HR = 1.78, 95% CI: 1.24-2.56). Analysis restricted to never smokers showed similar, though more imprecise, results. Consistently, we also observed an association between Cd exposure markers (blood and urine) and coronary heart disease, stroke, and peripheral artery disease. Moreover, Cd exposure was associated with atherogenic changes in lipid profile. High Cd exposure was associated with higher TC levels (OR = 1.48, 95% CI: 1.10-2.01), higher LDL-C levels (OR = 1.31, 95% CI 0.99-1.73) and lower HDL-C levels (OR = 1.96, 95% CI: 1.09-3.55). The mechanisms of atherogenic effect of cadmium may involve oxidative stress, inflammation, endothelial dysfunction, enhanced lipid synthesis, up-regulation of adhesion molecules, prostanoid dysbalance, as well as altered glycosaminoglycan synthesis.

Mercury and metabolic syndrome: a review of experimental and clinical observations.

A significant interrelation between heavy metal exposure and metabolic syndrome (MetS) development has been demonstrated earlier. Despite the presence of a number of works aimed at the investigation of the role of Hg in MetS development, the existing data remain contradictory. Therefore, the primary objective of the current work is to review the existing data regarding the influence of mercury on universal mechanisms involved in the pathogenesis of the development of MetS and its components. The brief chemical characterization of mercury is provided. The role of mercury in induction of oxidative stress has been discussed. In particular, Hg-induced oxidative stress may occur due to both prooxidant action of the metal and decrease in antioxidant enzymes. Despite the absence of direct indications, it can be proposed that mercury may induce endoplasmic reticulum stress. As it is seen from both in vivo and in vitro studies, mercury is capable of inducing inflammation. The reviewed data demonstrate that mercury affects universal pathogenetic mechanisms of MetS development. Moreover, multiple investigations have indicated the role of mercury in pathogenesis of MetS components: dyslipidemia, hypertension, insulin resistance, and obesity to a lesser extent. The present state of data regarding the interrelation between mercury and MetS denotes the following perspectives: (1) Further clinic-epidemiologic and experimental studies are required to estimate the association between mercury exposure and the development of MetS components, especially obesity; (2) Additional investigations of the possible effect of organism's mercury content modulation on MetS pathogenesis should be undertaken.

Speciation of Serum Copper and Zinc-Binding High- and Low-Molecular Mass Ligands in Dairy Cows Using HPLC-ICP-MS Technique.

The objective of the present study was assessment of the major copper and zinc species in dairy cow blood serum using a hybrid high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) technique. A total of seventeen 5-6-year-old female Simmental cows, cultivated in the Southern Ural region, were examined. Speciation of serum Cu and Zn was performed using chromatographic PerkinElmer Series 200 system equipped with Agilent Bio SEC-5 Column and docked with NexION 300D mass spectrometer. Analysis of serum 63Cu species revealed four major fractions containing 2.5% (A), 15.6% (B), 75.6% (C), and 11.9% (D) of total copper levels. The revealed fractions could be assigned to tetrameric and dimeric macroglobulin, ceruloplasmin, albumin, and low molecular mass (LMM) copper compounds, respectively. Minor fraction (E) containing <1% of total serum Cu levels may be represented by low-molecular mass Cu species. Speciation analysis also revealed four Zn fractions containing 6.3% (A), 16.9% (B), 71% (C), and 3% (D) of total Zn levels that may be attributed to zinc-bound tetrameric and dimeric macroglobulin, albumin, and Zn-amino acid compounds. Correlation analysis demonstrated that relative levels (%) of Zn-B (dimeric α2-macroglobulin), Zn-C (albumin), and Zn-D (LMM) fractions correlate inversely with Cu-A (monomeric α2-macroglobulin) (r = -0.600), Cu-D (albumin) (r = -0.696), and Cu-C (ceruloplasmin) (r = -0.652), respectively. The obtained data demonstrate the particular features of Zn and Cu transport in dairy cows that may be used for assessment of dietary status of trace elements.

Selenium, Zinc, Chromium, and Vanadium Levels in Serum, Hair, and Urine Samples of Obese Adults Assessed by Inductively Coupled Plasma Mass Spectrometry.

The objective of this study was to investigate of selenium (Se), zinc (Zn), chromium (Cr), and vanadium (V) levels in blood serum, hair, and urine of adult obese patients. A total of 199 lean and 196 obese subjects were enrolled in the study. Serum, hair, and urinary metal and metalloid analysis were performed by inductively coupled plasma mass spectrometry at NexION 300D (PerkinElmer Inc., USA). The results established that obese subjects were characterized by 47% and 30% lower serum Cr and V levels compared with controls, respectively, whereas serum Se levels exceeded control values by 9%. In contrast, hair Cr, Se, and V content in obese subjects exceeded the control values by 51%, 21%, and 50%, respectively. In turn, hair Zn levels were found to be significantly lower by 11% compared with the lean control values. In urine, the levels of V and Zn were found to be 30% and 18% higher in obese patients. Prevalence of hypertension in obese subjects was associated with a trend for impaired Se and Zn levels. In a regression model adjusted for age, gender, hypertension, atherosclerosis, and glucose intolerance, serum Cr, V, and hair Zn were inversely associated with body mass index (BMI), whereas hair Se was considered as the positive predictor. Our data allow proposing that the observed alterations may at least partially contribute to metabolic disturbances in obesity. In turn, monitoring of Se exposure in a well-nourished adult population is required to reduce its potential contribution to obesity.

Alterations in Blood Metabolic Parameters of Immature Mice After Subchronic Exposure to Cobalt Chloride.

The wide use of cobalt (Co) in food, industry, and medical devices requires full elucidation of its biological effects on tissues and organs. The aim was to assess serum metabolic alterations in immature mice after subchronic exposure to CoCl2. Pregnant ICR mice were subjected to a daily dose of 75 mg cobalt chloride/kg body weight (CoCl2x6H2O) 2-3 days before they gave birth, and treatment continued until days 25 and 30 after delivery. The compound was dissolved in and obtained with regular tap water. ICP-DRC-MS analysis showed significantly elevated serum Co2+ and diverse alterations in metabolic parameters of 25- and 30-day-old pups after exposure to CoCl2. Cholesterol and urea levels were significantly elevated in day 25 mice while HDL-C and LDL-C were reduced. In day 30, Co-exposed mice LDL-C and triglycerides were significantly increased while the total cholesterol level remained unchanged. Alkaline phosphatase was significantly reduced in day 25 Co-exposed mice. Blood glucose level of Co-exposed mice remained close to the untreated controls. Total protein content was slightly increased in day 30 mice. Co-exposure reduced albumin content and albumin/globulin ratio but increased significantly globulin content. Co administration showed strong correlation with cholesterol, urea, and HDL-C in both day 25 and 30 mice. Inverse correlation was found with alkaline phosphatase and albumin for day 25 and with triglycerides, globulin, and total protein content in day 30 Co-exposed mice. Subchronic CoCl2 exposure of immature mice induced significant changes in key metabolic parameters suggesting possible further disturbances in energy metabolism, osteogenesis, and reproduction.

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.

Isolevuglandins (isoLGs) as toxic lipid peroxidation byproducts and their pathogenetic role in human diseases.

Lipid peroxidation results in generation of a variety of lipid hydroperoxides and other highly reactive species that covalently modify proteins, nucleic acids, and other lipids, thus resulting in lipotoxicity. Although biological relevance of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) is well studied, the existing data on the role of isolevuglandins (isoLGs) in pathology are insufficient. Therefore, the objective of the present study was to review the existing data on biological effects of isoLG and isoLG adducts and their role in multiple diseases. Sixty four highly reactive levuglandin-like γ-ketoaldehyde (γ-KA, or isoketals, IsoK, or isolevuglandins, IsoLG) regio- and stereo-isomers are formed as products of arachidonic acid oxidation. IsoLGs react covalently with lysyl residues of proteins to form a stable adduct and intramolecular aminal, bispyrrole, and trispyrrole cross-links. Phosphatidylethanolamine was also shown to be the target for isoLG binding as compared to proteins and DNA. Free IsoLGs are not detectable in vivo, although isolevuglandin adduction to amino acid residues of particular proteins may be evaluated with liquid chromatography-tandem mass spectrometry. Adducts formed were shown to play a significant role in the development and maintenance of oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and inflammation. These, and more specific molecular pathways, link isoLG and isoLG-adduct formation to develop a variety of pathologies, including cardiovascular diseases (atherosclerosis, hypertension, heart failure), obesity and diabetes, cancer, neurodegeneration, eye diseases (retinal degeneration and glaucoma), as well as ageing. Hypothetically, isoLGs and isoLG adduct formation may be considered as the potential target for treatment of oxidative stress-related diseases.

A Case-Control Study of Essential and Toxic Trace Elements and Minerals in Hair of 0-4-Year-Old Children with Cerebral Palsy.

The objective of the present study was to assess hair essential and toxic trace elements and minerals in children with cerebral palsy in relation to age of the examinees. A total of 70 children with cerebral palsy and 70 healthy controls aged 0-4 years old were enrolled in the present study. The examined children were also divided into two age groups of those younger and older than 2 years old. Hair trace element content was assessed using ICP-MS at NexION 300D (PerkinElmer, USA). The obtained data demonstrate that hair boron was more than 2-fold lower in CP children as compared with the control group. At the same time, hair Na, Se, and V levels were 21%, 12%, and 20% lower when compared with healthy controls, respectively. It is also notable that a 9% and 28% decrease in hair Fe and Li levels respectively were nearly significant. The observed alterations were more profound in a younger group of patients. No significant group difference in hair toxic metal and metalloid levels was observed between the general cohorts of children with and without CP. In regression models, only hair Al and Ca contents were significantly associated with the presence of cerebral palsy, whereas hair Mg, Na, Ni, and Se levels were characterized as significant negative predictors. The observed alteration in trace element metabolism may also provide an additional link between cerebral palsy, psychomotor delay, and certain diseases, including diabetes, epilepsy, and osteoporosis. However, further studies using other substrates (blood, urine) or biomarkers are required.

The Impact of Perinatal Cobalt Chloride Exposure on Extramedullary Erythropoiesis, Tissue Iron Levels, and Transferrin Receptor Expression in Mice.

The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2-3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

Cobalt accumulation and iron-regulatory protein profile expression in immature mouse brain after perinatal exposure to cobalt chloride.

Developing brain is very sensitive to the influence of environmental factors during gestation and the neonatal period. The aim of the study is to assess cobalt and iron accumulation in the brain as well as changes in the expression of iron-regulatory proteins transferrin receptor 1, hepcidin, and ferroportin in suckling mice. Perinatal exposure to cobalt chloride increased significantly cobalt content in brain tissue homogenates of 18-day-old (d18) and 25-day-old (d25) mice inducing alterations in brain iron homeostasis. Higher degree of transferrin receptor 1 expression was demonstrated in cobalt chloride-exposed mice with no substantial changes between d18 and d25 mice. A weak ferroportin expression was found in 18-day-old control and cobalt-treated mouse brain. Cobalt exposure of d25 mice resulted in increased ferroportin expression in brain compared to the untreated age-matched control group. Hepcidin level in cobalt-exposed groups was decreased in d18 mice and slightly increased in d25 mice. The obtained data contribute for the better understanding of metal toxicity impact on iron homeostasis in the developing brain with further possible implications in neurodegeneration.

A Search for Similar Patterns in Hair Trace Element and Mineral Content in Children with Down's Syndrome, Obesity, and Growth Delay.

The objective of the present study was to perform comparative analysis of hair trace element and mineral levels in children with Down's syndrome, growth delay, and obesity in order to reveal common and specific patterns. Hair Zn (14, 7, and 15%), Ca (38%, 24%, and 47%), and Mg (33%, 31%, and 49%) levels in children with Down's syndrome, obesity, and growth delay were lower than the respective control values. At the same time, patients with Down's syndrome and growth delay were characterized by 27% and 21%, as well as 24% and 20% lower hair Co as well as Cu content than healthy examinees. Certain alterations were found to be disease-specific. Particularly, in Down's syndrome children, hair Cr, Fe, and V levels were significantly lower, whereas hair P content exceeded the control values. Obese children were characterized by significantly increased hair Cr content. At the same time, hair Mn and Si levels in children with growth delay were lower as compared with the controls. In regression models, all three studied diseases were considered as negative predictors of hair Cu content. Down's syndrome and growth delay, but not obesity, were inversely associated with hair Co content. Both Down's syndrome and obesity were inversely associated with hair Zn content. Based on the revealed similarities in altered hair element, content it is proposed that deficiency of essential elements may predispose Down's syndrome patients to certain syndrome comorbidities including growth delay and obesity, although further detailed studies are required.

Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study.

BACKGROUND: The objective of this pilot study was to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) status (hair, serum, and urine) and speciation (serum) in Parkinson's disease (PD) patients. METHODS: A pilot study involving a total of 27 subjects (13 PD patients, 14 controls) was performed. Serum, urine, and hair metal content was assessed using ICP-MS. Speciation analysis of Cu, Zn, Fe, and Mn was performed using a hybrid HPLC-ICP-MS system. RESULTS: Group comparisons did not reveal any significant group difference in serum Cu, Zn, Fe, and Mn total metal level between PD patients and controls. Speciation analysis revealed a significant decrease in Cu/ceruloplasmin copper in association with elevation of low-molecular weight species (amino acids)-bound copper. It is proposed that in PD, binding of Cu(II) ions to ceruloplasmin is reduced and free copper ions coordinate with low molecular weight ligands. The level of Mn-albumin complexes in PD patients was more than 4-fold higher as compared to the respective value in the control group. The observed difference may be considered as a marker of redistribution between high and low molecular weight ligands. CONCLUSIONS: Metal speciation is significantly affected in serum of PD-patients. These findings are indicative of the potential role of metal metabolism and PD pathogenesis, although the exact mechanisms of such associations require further detailed studies.

ICP-MS Assessment of Hair Essential Trace Elements and Minerals in Russian Preschool and Primary School Children with Attention-Deficit/Hyperactivity Disorder (ADHD).

The objective of the present study was to investigate the relationship between hair essential trace element and mineral content and ADHD in preschool (4-6 years old) and primary school children (6-10 years old) in relation to age and gender. Hair essential trace element and mineral content in 90 Russian children with ADHD and 90 age- and gender-matched neurotypical controls were assessed using inductively coupled plasma mass-spectrometry after microwave digestion. The obtained data demonstrate that hair Co, Cu, Mn, Si, and Zn contents in ADHD children was significantly reduced by 18%, 10%, 27%, 16%, and 19% as compared to the control values, respectively. The most significant decrease in children with ADHD was observed for hair Mg levels, being 29% lower than those in neurotypical children. After adjustment for age and gender, the observed difference in hair element content was more characteristic for preschool children and girls, respectively. Multiple linear regression analysis demonstrated that in a crude model (hair element levels as predictors), only hair Zn content was significantly inversely associated with ADHD (ß = - 0.169; p = 0.025). Adjustment for anthropometric parameters (model 2) did not increase the predictive ability of the model, although it improved the association between hair Zn and ADHD in children (ß = - 0.194; p = 0.014). Hypothetically, the observed alterations may at least partially contribute to neurobehavioral disturbances in children with ADHD. Moreover, the results of the present study raise the question about the potential benefits of Zn and Mg supplementation in children with ADHD. However, further detailed studies are required to investigate micronutrient deficiencies in ADHD.

Magnesium Status in Children with Attention-Deficit/Hyperactivity Disorder and/or Autism Spectrum Disorder.

OBJECTIVE: The objective of this study was to assess serum, hair, and urinary magnesium (Mg) levels in children with attention-deficit/ hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and both ASD and ADHD to reveal potential interactive effects. METHODS: A total of 148 boys aged 4-9 years old were enrolled in this study, including 44 children with ADHD, 40 pediatric patients with ASD, 32 patients with both ADHD and ASD, as well as 32 healthy neurotypical children. Hair, serum, and urinary Mg levels were assessed using inductively-coupled plasma mass spectrometry (ICP-MS). Laboratory quality control was performed using certified reference materials of human hair, plasma, and urine. RESULTS: No significant group difference in serum Mg levels was observed. Mg content in hair was found to be reduced in children with ADHD and ADHD+ASD compared to that in healthy controls by 11% and 15%, respectively. Urinary Mg levels in children with ADHD+ASD exceeded the control, ADHD, and ASD values by 51, 76, and 65%, respectively. Factorial analysis revealed significant contribution of ADHD to hair and urinary Mg levels. Multiple regression analysis demonstrated that hair and urinary Mg levels were considered as significant predictors of neurodevelopmental disorder complexity. CONCLUSION: We propose that impaired Mg status may provide a link between ADHD and ASD.

Zinc and respiratory tract infections: Perspectives for COVID­19 (Review).

In view of the emerging COVID­19 pandemic caused by SARS­CoV­2 virus, the search for potential protective and therapeutic antiviral strategies is of particular and urgent interest. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. Despite the lack of clinical data, certain indications suggest that modulation of zinc status may be beneficial in COVID­19. In vitro experiments demonstrate that Zn2+ possesses antiviral activity through inhibition of SARS­CoV RNA polymerase. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore. Indirect evidence also indicates that Zn2+ may decrease the activity of angiotensin­converting enzyme 2 (ACE2), known to be the receptor for SARS­CoV­2. Improved antiviral immunity by zinc may also occur through up­regulation of interferon α production and increasing its antiviral activity. Zinc possesses anti­inflammatory activity by inhibiting NF­κB signaling and modulation of regulatory T­cell functions that may limit the cytokine storm in COVID­19. Improved Zn status may also reduce the risk of bacterial co­infection by improving mucociliary clearance and barrier function of the respiratory epithelium, as well as direct antibacterial effects against S. pneumoniae. Zinc status is also tightly associated with risk factors for severe COVID­19 including ageing, immune deficiency, obesity, diabetes, and atherosclerosis, since these are known risk groups for zinc deficiency. Therefore, Zn may possess protective effect as preventive and adjuvant therapy of COVID­19 through reducing inflammation, improvement of mucociliary clearance, prevention of ventilator­induced lung injury, modulation of antiviral and antibacterial immunity. However, further clinical and experimental studies are required.

Selenium and Selenoproteins in Adipose Tissue Physiology and Obesity.

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.