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Summary Background The present study has the objective to assess the zinc (Zn), copper (Cu), and oxysterols plasma levels in type 1 (DM1) (n = 26) and type 2 (DM2) (n = 80) diabetes patients, as compared to healthy controls (n = 71), in order to testify whether metal levels may have a significant impact on the association between oxysterols and diabetes. Methods Plasma trace elements and plasma oxysterols were assessed using atomic absorption spectrometry and LC-MS/MS, respectively. Lifestyle, smoking status, alcohol intake, and drug usage, as well as microvascular complications, were also monitored and reported. Results The obtained data demonstrated that both DM1 and DM2 patients were characterized by significantly elevated HbA1c, FBG, TC, LDL-C, VLDL-C, and TG levels as compared to controls. Plasma Zn levels and Zn/Cu ratio in DM1 and DM2 patients were about 3- and 2-fold lower than controls. No significant differences in plasma Cu levels were reported. The 7-ketocholesterol (7-kchol) levels in DM1 and DM2 patients exceeded these values in healthy individuals by 2.5 and 5-fold, respectively. Similarly, cholestan-3β, 5α, 6β-triol (chol-triol) levels were more than 3- and 6-fold higher when compared to the respective values in non-diabetic controls. In regression models decreased plasma Zn and elevated oxysterol levels were significantly associated with HbA1c and fasting plasma glucose levels, after adjustment for anthropometric and clinical variables, as well as routine biochemical markers. Conclusions Plasma Zn concentration is inversely associated with both 7-kchol and chol-triol levels. Assessment of Zn and oxysterol levels may be used both for risk assessment and as targets for the treatment of diabetes mellitus.

The neurotransmitter dopamine is a neuromodulator in the positive and negative regulation of brain circuits. Dopamine insufficiency or overload has been implicated in aberrant activities of neural circuits that play key roles in the pathogenesis of neurological and psychiatric diseases. Dopaminergic neurons are vulnerable to environmental insults. The neurotoxin methylmercury (MeHg) produces dopaminergic neuron damage in rodent as well as in Caenorhabditis elegans (C. elegans) models. Previous studies have demonstrated the utility of C. elegans as an alternative and complementary experimental model in dissecting out mechanism of MeHg-induced dopaminergic neurodegeneration. However, a sensitive pathological change that marks early events in neurodegeneration induced by environmental level of MeHg, is still lacking. By establishing a chronic exposure C. elegans model, for the first time, we have shown the propensity of MeHg (5 μM, 10 days) to induce bright puncta of dat-1::mCherry aggreagtes in the dendrites of cephalic (2 CEPs) dopaminergic neurons in a dose- and time-dependent manner, while these changes were not found in other dopaminergic neurons: anterior deirids (2 ADEs) and posterior deirids (2 PDEs), cholinergic neurons (2 AlYs) or glutamatergic neurons (2 PVDs). The bright puncta appear as an aggregation of mCherry proteins accumulating in dendrites. Further staining shows that the puncta were not inclusions in lysosome, or amyloid protein aggregates. In addition, features of the puncta including enlarged sphere shape (0.5 – 2 μm diameters), bright and accompanying with the shrinkage of the dendrite suggest that the puncta are likely composed of homologous mCherry molecules packaged at the dendritic site for exportation. Moreover, in the glutathione S-transferase 4 (gst-4) transcriptional reporter strain and RT-PCR assay, the expression levels of gst-4 and tubulins (tba-1 and tba-2) genes were not significantly modified under this chronic exposure paradigm, but gst-4 did show significant changes in an one day exposure paradigm. Collectively, these results suggest that CEP dopaminergic neurons are a sensitive target of MeHg, and the current exposure paradigm could be used as a model to investigate mechanism of dopaminergic neurotoxicity.

Data on the association between aluminium (Al) exposure and obesity and/or metabolic syndrome are insufficient. The objective of the present study was to investigate the association between hair and urine Al levels and obesity.A total of 206 lean and 205 obese non-occupationally exposed subjects (30-50 y.o.) were enrolled in the study. Hair and urine Al levels were assessed with ICP-MS. Laboratory quality control was performed using the certified reference materials of human hair, plasma, and urine.Hair and urinary Al levels in obese subjects were significantly higher by 31% and 46% compared to the control levels, respectively. The presence of hypertension (41% cases), atherosclerosis (8%), type 2 diabetes mellitus (10%), and non-alcoholic fatty liver disease (NAFLD) (53%) in obese patients were not associated with Al levels in the studied subjects. An overall multiple regression model established urinary Al levels (β = 0.395; p 0.001), hypertension (β = 0.331; p 0.001) and NAFLD (β = 0.257; p = 0.003) were significantly and directly associated with BMI. Hair Al levels were found to be border-line significantly related to BMI after adjustment for several confounders (β = -0.205; p = 0.054).Aluminium body burden is associated with increased body weight, although the causal relationship between Al exposure and obesity is not clear. Both clinical and experimental studies are required to further investigate the impact of Al exposure on metabolic parameters in obesity and especially direct effects of Al in adipose tissue.

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.

Chronis rhinosinusitis is considered as a widespread public health issue with a prevalence of 10%. The disease significantly reduces quality of life and increases the risk of cardiovascular diseases as well as certain forms of cancer. Alteration of mucociliary clearance frequently observed in the patients and plays a significant role in disease pathogenesis. Certain studies have demonstrated that patients with chronic rhinosinusitis are characterized by significant reduction of essential trace elements and toxic metal overload. However, the particular mechanisms of the role of trace element dysbalance in chronic rhinosinusitis are unclear. We hypothesize that exposure to toxic trace elements (arsenic, nickel, cadmium) damages ciliary mucosal epithelium thus affecting mucociliary transport. In turn, altered mucociliary transport results in reduced removal of the inhaled metal-containing particles from nasal mucosa leading to their absorption and further aggravation of toxicity. Essential trace elements (zinc, selenium) play a significant role in regulation of mucociliary transport and immunity, thus their deficiency (either dietary or due to antagonism with toxic metals) may be associated with impaired functions and increased toxic metal toxicity. Therefore, a vicious circle involving metal accumulation and toxicity, essential element deficiency, impairment of mucociliary transport and metal particle removal, resulting in further accumulation of metals and aggravation of toxic effects is formed. The present hypothesis is supported by the findings on the impact of trace elements especially zinc and arsenic on mucociliary clearance, the role of mucociliary transport in heavy metal particles elimination from the airways, trace element dysbalance in chronic rhinosinusitis, as well as toxic and essential metal antagonism. The data from hypothesis testing and its verification may be used for development of therapeutic approach for management of chronic rhinosinusitis. Particularly, the use of essential elements (zinc, selenium) may reduce toxic metal toxicity thus destroying the vicious circle of heavy metal exposure, toxicity, alteration of mucociliary clearance, and aggravation of chronic rhinosinusitis. Essential element supplementation may be considered as a tool for management of chronic refractory rhinosinusitis. In addition, analysis of essential and toxic trace element status may provide an additional diagnostic approach to risk assessment of chronic rhinosinusitis in highly polluted environments.

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 (β = 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.

The present study aims to review epidemiological and experimental toxicology studies published over the last two decades linking mercury (Hg) exposure and carcinogenesis, with a special emphasis on the potential underlying mechanisms. While some epidemiological studies have observed a strong association between environmental/occupational Hg exposure levels, measured in blood, toenail, and hair, and cancer risk and mortality, others failed to reveal any association. In experimental models, high-dose Hg exposure has been linked with cytotoxicity, whereas low-dose exposure was posited to induce proliferative responses in both normal and cancerous cells by interference with estrogen receptor, ERK1/2, JNK, NADPH-oxidase and, potentially, Nrf2 signaling. Combined with reduced apoptosis and pro-survival signaling upon low-dose Hg exposure, accumulation of DNA lesions in cells may predispose to an increased risk of malignant transformation. In addition, the pro-oxidant activity of Hg species may induce oxidative DNA modifications and inhibits DNA repair mechanisms. Furthermore, epigenetic effects of Hg exposure seem to contribute to the carcinogenic activity, although the particular mechanisms have yet to be characterized. Therefore, even after 20 years of research, one cannot consider Hg as a non-carcinogenic agent, whereas specific mechanisms of Hg-induced toxicity may promote carcinogenic risk.

Multiple medical, lifestyle, and environmental conditions, including smoking and particulate pollution, have been considered as risk factors for COronaVIrus Disease 2019 (COVID-19) susceptibility and severity. Taking into account the high level of toxic metals in both particulate matter (PM2.5) and tobacco smoke, the objective of this review is to discuss recent data on the role of heavy metal exposure in development of respiratory dysfunction, immunotoxicity, and severity of viral diseases in epidemiological and experimental studies, as to demonstrate the potential crossroads between heavy metal exposure and COVID-19 severity risk. The existing data demonstrate that As, Cd, Hg, and Pb exposure is associated with respiratory dysfunction and respiratory diseases (COPD, bronchitis). These observations corroborate laboratory findings on the role of heavy metal exposure in impaired mucociliary clearance, reduced barrier function, airway inflammation, oxidative stress, and apoptosis. The association between heavy metal exposure and severity of viral diseases, including influenza and respiratory syncytial virus has been also demonstrated. The latter may be considered a consequence of adverse effects of metal exposure on adaptive immunity. Therefore, reduction of toxic metal exposure may be considered as a potential tool for reducing susceptibility and severity of viral diseases affecting the respiratory system, including COVID-19., Graphical abstract Image 1

The principles and practice of assessing the human body nutritional status or its environmental exposure through hair bioelement analysis are presented; herein the term "bioelements" is used as a common denominator for the major elements, trace elements and ultra-trace elements that are found in the human body. The accumulation of bioelements in the hair followed the statistical Power Law and the resulting sigmoid curve can be zoned into five regions in the ascending order of abundance (Low, Marginal, Adequate, High, and Excessive). The Adequate linear region of the bioassay sigmoid curve may be further subdivided into Low adequate, Recommended, and Ample adequate sub regions in a 60:30:10 ratio. Phosphorus was the most invariant bioelement since its hair concentration varies minimally regardless of the geographical place of living, the twenty years' time interval between the analyses, sex, race and instrumentation, i.e., atomic absorption spectrometry (AAS) atomic emission spectrometry (AES), and inductively plasma mass spectrometry (ICP MS). The osteotrophic (bone seeking) bioelements: Ca, Mg, and Sr, were 2.5 times more abundant in the hair of women than men. Two principal electrolytes of the body (Na, K) of the multi-bioelement hair profile were markedly increased in the depressed subjects diagnosed according to the American Psychiatric Association MSD-IV classification criteria. This increase in the hair Na and K of the depressed subjects was also associated with the decrease of vasopressin in the peripheral blood. The factor analysis revealed strong association of depression with sex (women > men in a 2.5:1 ratio), and with the metals from the Nieboer-Richardson series which form strong covalent bonds with proteins. We propose that the biological roots of depression are related to the non-specific impairment of the intracellular osmotic balance and ionic gradient due to the Na+K+ATPase failure from whatever cause acting either separately or in combination. We also put forward the idea of how children's autism may be related to a disproportional growth rate of various organs and tissues if children are fed up to their maximal genetic growth capacity. Finally, we have suggested the hypothesis on how the syntax or integration of the internal metabolic wiring of the bioelements in the body may occur. We have suggested the hypothetical existence of two complex distinct five-bioelement "rotors", the P-rotor and the N-rotor, where the P-rotor integrates the mileau interior (Na, K) ions with the perception/excitability (Mg, Ca) ions. Thus, the complex five element interdependence is cross related to P which provides the energy from the phosphorus of the DNA nucleotide backbone. The hair multi-bioelement profile analysis allows us to envisage the more complex structural metabolic features that bioelements are playing in our bodies.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, verbal and non-verbal communication, and stereotypic behaviors. Many studies support a significant relationship between many different environmental factors in ASD etiology. These factors include increased daily exposure to various toxic metal-based environmental pollutants, which represent a cause for concern in public health. This article reviews the most relevant toxic metals, commonly found, environmental pollutants, i.e., lead (Pb), mercury (Hg), aluminum (Al), and the metalloid arsenic (As). Additionally, it discusses how pollutants can be a possible pathogenetic cause of ASD through various mechanisms including neuroinflammation in different regions of the brain, fundamentally occurring through elevation of the proinflammatory profile of cytokines and aberrant expression of nuclear factor kappa B (NF-κB). Due to the worldwide increase in toxic environmental pollution, studies on the role of pollutants in neurodevelopmental disorders, including direct effects on the developing brain and the subjects’ genetic susceptibility and polymorphism, are of utmost importance to achieve the best therapeutic approach and preventive strategies.

The primary objective of the present study was to review the impact of Cd exposure on gut microbiota and intestinal physiology, as well as to estimate whether gut may be considered as the target for Cd toxicity. The review is based on literature search in available databases. The existing data demonstrate that the impact of Cd on gut physiology is two-sided. First, Cd exposure induces a significant alteration of bacterial populations and their relative abundance in gut (increased Bacteroidetes-to-Firmicutes ratio), accompanied by increased lipopolysaccharide (LPS) production, reflecting changed metabolic activity of the intestinal microbiome. Second, in intestinal wall Cd exposure induces inflammatory response and cell damage including disruption of tight junctions, ultimately leading to increased gut permeability. Together with increased LPS production, impaired barrier function causes endotoxinemia and systemic inflammation. Hypothetically, Cd-induced increase gut permeability may also result in increased bacterial translocation. On the one hand, bacteriolysis may be associated with aggravation of endotoxemia. At the same time, together with Cd-induced impairment of macrophage inflammatory response, increased bacterial translocation may result in increased susceptibility to infections. Such a supposition is generally in agreement with the finding of higher susceptibility of Cd-exposed mice to infections. The changed microbiome metabolic activity and LPS-induced systemic inflammation may have a significant impact on target organs. The efficiency of probiotics in at least partial prevention of the local (intestinal) and systemic toxic effects of cadmium confirms the role of altered gut physiology in Cd toxicity. Therefore, probiotic treatment may be considered as the one of the strategies for prevention of Cd toxicity in parallel with chelation, antioxidant, and anti-inflammatory therapy.

The chelating thiols dimercaptosuccinate (DMSA) and dimercaptopropane sulfonate (DMPS) are effective in enhancing urinary excretion of mercury and lead. However, strategies for mobilization of toxic metals from aged brain deposits may require combined use of a water soluble agent, removing circulating metal into urine, as well as lipophilic chelator, being used to facilitate the brain-to-blood mobilization. Pb(II) and Hg(II) ions are coordinated with DMSA through one COOH and one SH group. However Pb(II) can bind with racemic DMSA through two SH groups in non-aqueous solvents (when COOH groups are esterified). Generally, such Pb(II) and Hg(II) complexes have a composition of 1:1 and 1:2. However, binuclear and polynuclear species with DMSA like 2:1, 2:2, 2:3, 3:3 have been identified for Hg(II) ions. Both Pb(II) and Hg(II) ions are formed with BAL 1:1 and 1:2 complexes with coordination through two mercapto groups. Early experiments showed promising results with the SH–dextran–British anti-lewisite (BAL) combination. Later insight indicates that the DMPS–BAL could be preferred in cases of long-term Hg exposure. In cases of lead poisoning DMSA has been the recommended antidote due to its low toxicity. However, DMSA is distributed extracellularly, and its efficacy might be improved when combined with a brain-to-blood shuttling agent. Thus it has been found that the ionophore Monensin can improve its effect by increasing the egress of intracellularly deposited Pb. Previously, BAL was combined with ethylenediaminetetraacetic acid (EDTA) in severe cases. Today, it is reasonable that low-dosed BAL can facilitate mobilization of Pb from brain to blood during DMSA-treatment.

Background The existing data demonstrate the potential role of trace elements in nasal mucociliary clearance, although the association between trace element and mineral status and ciliary function in children with chronic rhinosinusitis is insufficiently studied. Therefore, the objective of the present study is evaluation of trace element and mineral status and mucociliary function in pediatric CRS patients before and after functional endoscopic sinus surgery. Methods The present study involved 30 children with chronic rhinosinusitis without nasal polyps. During this follow-up the patients were examined preoperatively (point 0), underwent functional endoscopic sinus surgery, and were repeatedly examined at three months postoperatively (point 1). At both points the patients were subjected to quality-of-life assessment using SNOT-20 questionnaire; endoscopic and computer tomography examination of the nasal sinuses; evaluation of ciliary function and mucosal cytology using high-speed videomicroscopy; assessment of blood count and inflammatory markers; as well as analysis of trace element and mineral levels in whole blood, serum, and hair using inductively-coupled plasma mass-spectrometry. Results The obtained data demonstrate that endoscopic sinus surgery significantly improved sinonasal pathology in children with chronic rhinosinusitis, as evidenced by significantly reduced Lund-Mackay, Lund-Kennedy, and SNOT-20 scores. At the same time, no significant improvement of ciliary functions or mucosal cytology was observed postoperatively. Trace element status assessment demonstrated that postoperative serum Zn, whole blood Mg and Cu were significantly lower as compared to preoperative values. In contrast, serum Mn and Cr, as well as whole blood Cr and hair Se were characterized by a significant increase at three months postoperatively. Multiple linear regression analysis demonstrated that serum Zn is significantly associated with the number of ciliated cells and cell viability, whereas serum Mn and whole blood Cu concentrations are inversely associated with cell viability and ciliary length, respectively. Hair Se was found to be associated with the number of neutrophils in the mucosa biopsy. Conclusion Redistribution of trace elements and minerals may at least partially mediate prolonged recovery of mucosal ciliary function in children with chronic rhinosinusitis in three months after functional sinus surgery, although the particular mechanisms of these alterations in trace element levels are to be discovered.

Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmium exposure on incidence of diabetes mellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio=1.38, 95% confidence interval 1.12-1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated.

The objective of the present study was to assess hormonal and trace element status in men suffering from acute ischemic stroke. Methods 21 acute ischemic stroke patients and 21 age- and body mass index-matched healthy volunteers were enrolled in the study. Serum trace elements were assessed using inductively coupled plasma mass spectrometry. Serum hormones and brain damage markers were estimated using enzyme-linked immunosorbent assay. Results Ischemic stroke patients are characterized by significantly higher levels of total and free triiodothyronine (T3), anti-thyroid peroxidase antibodies (Anti-TPO-Ab), prolactin, and cortisol, whereas the level of thyroid stimulating hormone (TSH) was decreased. Serum B, Cu, Li, Mn, Ni, Pb, Se, V, and Zn in stroke significantly exceeded the control values, whereas the level of Co and Fe was decreased. Correlation analysis revealed a significant association between serum B and T3, Anti-TPO-Ab, and iodine concentration; serum Li and Sr levels − with circulating TSH, free T3, and Anti-TPO-Ab; and V concentration − with total T3 and I levels. The following positive relationships were also revealed: Co − TSH, Mn − free T3, Zn − free T3. Multiple linear regression demonstrated that Co, I, and Li were directly related to circulating TSH levels, whereas V concentration was negatively interrelated. In turn, only serum Li levels were characterized by a significant direct relationship with free T3 values. Conclusion Generally, the obtained data demonstrate that altered serum trace elements are associated with thyroid dysfunction in acute ischemic stroke patients. However, the causal relationship should be estimated.

The iodine deficiency disorders (IDD) include a variety of disturbances such as decreased fertility, increased perinatal and infant mortality, impaired physical and intellectual development, mental retardation, cretinism, hypothyroidism, and endemic goiter (EG). The occurrence of the latter is determined by interplay between genetic and environmental factors. The major environmental factor is iodine status that is required for normal thyroid hormone synthesis. However, other factors like intake of micronutrients and goiterogens also have a significant impact. Essential and toxic trace elements both play a significant role in thyroid physiology. We hypothesize that in terms of overexposure boron may serve as a potential goiterogen. In particular, it is proposed that boron overload may impair thyroid physiology ultimately leading to goiter formation. Certain studies provide evidential support of the hypothesis. In particular, it has been demonstrated that serum and urinary B levels are characterized by a negative association with thyroid hormone levels in exposed subjects. Single indications on the potential efficiency of B in hypothyroidism also exist. Moreover, the levels of B were found to be interrelated with thyroid volume in children environmentally exposed to boron. Experimental studies also demonstrated a significant impact of boron on thyroid structure and hormone levels. Finally, the high rate of B cumulation in thyroid may also indicate that thyroid is the target for B activity. Chemical properties of iodine and boron also provide a background for certain competition. However, it is questionable whether these interactions may occur in the biological systems. Further clinical and experimental studies are required to support the hypothesis of the involvement of boron overexposure in goiter formation. If such association will be confirmed and the potential mechanisms elucidated, it will help to regulate the incidence of hypothyroidism and goiter in endemic regions with high boron levels in soil and water.

Iron (Fe) deficiency is considered as the most common nutritional deficiency. Iron deficiency is usually associated with low Fe intake, blood loss, diseases, poor absorption, gastrointestinal parasites, or increased physiological demands as in pregnancy. Nutritional Fe deficiency is usually treated with Fe tablets, sometimes with Fe-containing multimineral tablets. Trace element interactions may have a significant impact on Fe status. Existing data demonstrate a tight interaction between manganese (Mn) and Fe, especially in Fe-deficient state. The influence of Mn on Fe homeostasis may be mediated through its influence on Fe absorption, circulating transporters like transferrin, and regulatory proteins. The existing data demonstrate that the influence of zinc (Zn) on Fe status may be related to their competition for metal transporters. Moreover, Zn may be involved in regulation of hepcidin production. At the same time, human data on the interplay between Fe and Zn especially in terms of Fe-deficiency and supplementation are contradictory, demonstrating both positive and negative influence of Zn on Fe status. Numerous data also demonstrate the possibility of competition between Fe and chromium (Cr) for transferrin binding. At the same time, human data on the interaction between these metals are contradictory. Therefore, while managing hypoferremia and Fe-deficiency anemia, it is recommended to assess the level of other trace elements in parallel with indices of Fe homeostasis. It is supposed that simultaneous correction of trace element status in Fe deficiency may help to decrease possible antagonistic or increase synergistic interactions.

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.

Mercury (Hg) is an environmental toxicant being present in the environment as elemental Hg (Hg0), inorganic and organic Hg compounds. The nervous system is supposed to be the key target for Hg toxicity. Research indicates that selenium (Se) may be used as a protective agent against Hg neurotoxicity. Therefore, the aim of this review is to examine new implications of the molecular biology of Hg neurotoxicity, and specifically to focus on the influence of Se compounds and interfering thiols on Hg neurotoxicity at the molecular level. Mercury and Se form stable coordination compounds, and Hg species are characterized by higher affinity to selenol groups as compared to thiol groups. Therefore, Se-containing molecules are targets for Hg binding that may at least partially mediate the biological outcome of Hg-Se interaction. Molecular interaction between these elements also involves mutual interaction between Hg and various selenoproteins. Experimental data demonstrate that Se treatment modifies brain Hg retention, modulates neurotoxicity and oxidative stress in the nervous tissue of animals. Human data also indicate that molecular interaction between Hg and Se may have a significant influence on neurodevelopment, brain functioning, and neurodegeneration. It is hypothesized that the effectiveness of Se protection against Hg neurotoxicity may be determined by the dose of elements as well as their particular chemical forms. Further studies are required to estimate the intimate mechanisms of Hg and Se interaction in vivo.

The primary objective of the study was to assess the level of metals and trace elements in liver, serum, and hair of rats with diet-induced non-alcoholic fatty liver disease (NAFLD) using inductively coupled plasma dynamic reaction cell mass spectrometer (ICP-DRC-MS). 56 female 3-months-old Wistar rats divided into two equal groups were fed either standard (10% calories from fat) or high-fat high-carbohydrate diet (60% calories from fat in chow and 10% sucrose solution) for 6 weeks. Serum was examined for insulin resistance markers, lipid profile, and alanine aminotransferase (ALT) activity. Liver histology was assessed after hematoxylin and eosin staining. Metal and trace element concentrations were assessed by means of ICP-DRC-MS. Overfed animals were characterized by higher values of morphometric parameters. Liver examination revealed large and small droplet steatosis, hepatocyte ballooning and necrosis, being characteristic for NAFLD. Animals with NAFLD were characterized by insulin resistance, atherogenic changes of lipid profile and increased ALT activity. Significantly decreased hepatic Co, Cu, I, Li, Mn, Se, Zn levels were observed in rats with NAFLD. At the same time, only hepatic Mn and Se levels remained decreased after adjustment for total protein. Overfed animals were characterized by significantly lower I, Li, and Mn levels in blood serum, whereas concentration of Co, Se, V, and Sr exceeded the control values. In general, the results of the study demonstrate that NAFLD significantly affects metal and trace element status in experimental animals.

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.

Background ASD is associated with complex metabolic alterations including amino acid metabolism. However, the existing data are contradictory. Therefore, the objective of the present study was investigation of serum amino acid levels in children with ASD. Methods A total of 97 boys (3–14 y.o.) including 64 children with diagnosed ASD and 33 neurotypical age-matched controls were enrolled in the current study. Assessment of serum amino acid levels was performed using high-pressure liquid chromatography (HPLC) with UV-detection. ClinChek® Plasma Control was used for laboratory quality control. Statistical analysis was performed using analysis of covariance (ANCOVA) with adjustment for age and Bonferroni correction. Results. The obtained data demonstrate that the mean levels of Arg, Gln, His, Leu, Lys, Phe, Ser, Tau, Thr, and Trp in ASD were 28 %, 23 %, 20 %, 17 %, 21 %, 15 %, 21 %, 24 %, 19 %, and 22 % lower as compared to the control values, respectively. Serum Hypro and Tyr levels in children with ASD were more than 2-fold and 11 % higher as compared to the control values, respectively. Multiple regression analysis demonstrated that serum Leu and Ser (negatively), and Hypro and Tyr levels (positively) were significantly associated with ASD. Conclusions The obtained data demonstrate that children with ASD are characterized by a trend to multiple amino acid deficiency in parallel with elevation of serum Tyr and Hypro levels. The latter may provide a link between ASD and joint hypermobility. In turn, deficiency of other amino acids may impair neurobehavior in ASD due to their role as neuromediators or their precursors.

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.

Essential trace elements and minerals play a significant role in neurodevelopment. Although certain studies demonstrated impaired essential trace element and mineral status in children with ADHD, the existing data are insufficient. The objective of the present study was to assess serum trace element and mineral levels in children with ADHD.Serum trace element and mineral levels in 68 children with ADHD and 68 neurotypical controls were assessed using ICP-MS at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA).Serum Cr, Mg, and Zn levels in children with ADHD were 21 % (p = 0.010), 4 % (p = 0.005), and 7 % (p = 0. 001) lower as compared to the healthy controls, respectively. In turn, serum Cu/Zn values were 11 % higher than those in the control group. Age and gender had a significant impact on serum element levels in ADHD. Particularly, preschool children were characterized by significantly increased Cu (+8 %; p = 0.034), and Cu/Zn (+19 %; p0.001) values, whereas serum Zn (-9 %; p = 0.004) level was decreased. In primary school-aged children only 6 % (p = 0.007) lower Mg levels were observed. Both boys and girls with ADHD were characterized by 8 % (p = 0.016) lower serum Zn levels and 10 % (p = 0.049) higher Cu/Zn values when compared to neurotypical girls. Boys with ADHD also had significantly higher Cu/Zn, exceeding the respective control values by 12 % (p = 0.021), predominantly due to a 7 % (p = 0.035) decrease in serum Zn. Serum Mg levels were also found to be significantly lower than those in neurotypical children by 5 % (p = 0.007). In adjusted regression models serum Cr (β=-0.234; p = 0.009) and Cu/Zn (β = 0.245; p = 0.029) values were significantly associated with ADHD, respectively. Two-way ANOVA revealed a significant impact of ADHD on Cr, Mg, Zn, and Cu/Zn, whereas age was associated with Cu, I, Mg, Mo, and Cu/Zn, whereas gender accounted only for variability in serum Mn levels. Principal component analysis (PCA) also revealed significant contributions of Mg, Zn, and Cu/Zn values to ADHD variability.Hypothetically, the observed decrease of essential trace elements, namely Mg and Zn, and elevation of Cu/Zn may significantly contribute to the risk of ADHD or its severity and/or comorbidity.

The primary objective of the current study is to investigate the relationship between adipose tissue chromium and vanadium content and adipose tissue dysfunction in a model of diet-induced obesity. A total of 26 female Wistar rats were fed either standard or high-fat diet (31.6% of fat from total caloric content) for 3 months. High-fat-feeding resulted in 21 and 33% decrease in adipose tissue chromium and vanadium content, respectively. No change was seen in hair chromium or vanadium levels. Statistical analysis revealed a significant inverse correlation of adipose tissue Cr and V with animal morphometric parameters and adipocyte size. Significant inverse dependence was observed between adipose tissue Cr and V and serum leptin and proinflammatory cytokines' levels. At the same time, adipose tissue Cr and V levels were characterized by positive correlation between serum adiponectin and adiponectin/leptin ratio. Adipose tissue Cr and V were inversely correlated (p0.05) with insulin and homeostatic model assessment insulin resistance index (HOMA-IR) levels. Cr and V concentrations were not correlated with serum glucose in either high-fat fed or control rats; however, both serum glucose and HOMA-IR levels were significantly higher in high-fat fed, compared to control, rats. The results allow to hypothesize that impairment of adipose tissue Cr and V content plays a certain role in the development of adipose tissue endocrine dysfunction in obesity.

Endemic goitre is a primary pathology of thyroid gland and critical medico social problem in many countries. A dominant cause of endemic goitre is iodine deficiency. However, besides primary iodine deficiency, the goitre may probably develop due to effects of other bioelement imbalances, essential to thyroid function maintenance. Here we studied 44 cases of endemic goitre in prepubertal children (7-10 y.o.) living in iodine-adequate territory. Thyroid volume was estimated by ultrasonometry. Main bioelements (Al, Ca, Cd, Co, Cr, Cu, Fe, Hg, I, Mg, Mn, Pb, Se, Si, Zn) were determined in hair samples by ICP-OES/ICP-MS method. Relationships between hair content of bioelements and thyroid gland size were estimated by multiple regressions. The regression model revealed significant positive relations between thyroid volume and Cr, Si, Mn contents. However, the actual factor of thyroid gland increase was only Si excess in organism. Significant negative relations of thyroid volume were revealed with I, Mg, Zn, Se, Co and Cd. In spite of this, the actual factors of thyroid gland volume increasing were I, Co, Mg and Se deficiency. Total bioelement contribution in thyroid impairment was estimated as 24%. Thus, it was suggested that endemic goitre in iodine-adequate territory can be formed by bioelement imbalances, namely Si excess and Co, Mg, Se shortage as well as endogenous I deficiency in spite of iodine-adequate environment.