Anatoly V. Skalny

The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: The potential influence of zinc status as an example

There is increasing evidence that human pregnancy outcome can be significantly compromised by suboptimal maternal nutritional status. Poor diet results in a maternal–fetal environment in which the teratogenicity of other insults such as alcohol might be amplified. As an example, there is evidence that zinc (Zn) can interact with maternal alcohol exposure to influence the risk for fetal alcohol spectrum disorders (FASD). Studies with experimental animals have shown that the teratogenicity of alcohol is increased under conditions of Zn deficiency, whereas its teratogenicity is lessened when animals are given Zn‐supplemented diets or Zn injections before the alcohol exposure. Alcohol can precipitate an acute‐phase response, resulting in a subsequent increase in maternal liver metallothionein, which can sequester Zn and lead to decreased Zn transfer to the fetus. Importantly, the teratogenicity of acute alcohol exposure is reduced in metallothionein knockout mice, which can have improved Zn transfer to the conceptus relative to wild‐type mice. Consistent with the above, Zn status has been reported to be low in alcoholic women at delivery. Preliminary data from two basic science and clinical nutritional studies that are ongoing as part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders support the potential role of Zn, among other nutritional factors, relative to risk for FASD. Importantly, the nutrient levels being examined in these studies are relevant to general clinical populations and represent suboptimal levels rather than severe deficiencies. These data suggest that moderate deficiencies in single nutrients can act as permissive factors for FASD, and that adequate nutritional status or intervention through supplementation may provide protection from some of the adverse effects of prenatal alcohol exposure.

Mutual interaction between iron homeostasis and obesity pathogenesis

Obesity is identified as an important medical problem. One of the pathologic conditions observed in obesity is systemic iron deficiency and hypoferremia. Along with a large number of studies indicating disturbed iron homeostasis in obesity, recent data indicate a cause-effect relationship between iron status and obesity-related pathologies. The primary objective of the article is to consider two aspects of the iron-obesity interplay: (1) the mechanisms leading to impaired iron balance, and (2) the pathways of iron participation in obesity-related pathogenesis. While considering disturbance of iron homeostasis in obesity, a number of potential mechanisms of hypoferremia are proposed. At the same time, the inflammation of obesity and obesity-related hepcidin and lipocalin 2 hyperproduction seem to be the most probable reasons of obesity-related hypoferremia. Oversecretion of these proteins leads to iron sequestration in reticuloendothelial system cells. The latter also leads to increased adipose tissue iron content, thus producing preconditions for adverse effects of local iron overload. Being a redox-active metal, iron is capable of inducing oxidative stress as well as endoplasmic reticulum stress, inflammation and adipose tissue endocrine dysfunction. Iron-mediated mechanisms of toxicity may influence aspects of obesity pathogenesis possibly even leading to obesity aggravation. Thus, a mutual interaction between disturbance in iron homeostasis and obesity pathogenesis is proposed. All sides of this interaction should be considered to design new therapeutic approaches to the treatment of disturbed iron homeostasis in obesity.

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.

The role of cadmium in obesity and diabetes

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.

Reference values of hair toxic trace elements content in occupationally non-exposed Russian population.

A total of 5908 occupationally non-exposed adults (4384 women and 1524 men) living in Moscow and Moscow region were involved in the current investigation. Hair Al, As, Be, Bi, Cd, Hg, Li, Ni, Pb, Sn, and Sr content was estimated by inductively-coupled plasma mass spectrometry using NexION 300D. Men are characterized by significantly higher hair Al, As, Cd, Hg, Li, and Pb content. At the same time, hair levels of Bi, Ni, Sn, and Sr were significantly higher in women. Consequently, the reference ranges were estimated for male, female, and general cohort as coverage intervals in accordance with IUPAC recommendations.

Hair Toxic Element Content in Adult Men and Women in Relation to Body Mass Index

The primary objective of the current study was to estimate the hair toxic metal content in adults in relation to body mass index. A total of 1,229 persons including 719 women and 510 men were examined. All subjects were divided into two age groups: 1 and 2 periods of adulthood. All men and women were also subdivided into groups in relation to their values of body mass index (BMI): underweight, normal weight, overweight and obese. Hair aluminium (Al), beryllium (Be), cadmium (Cd), mercury (Hg), lead (Pb) and tin (Sn) content was evaluated using mass spectrometry with inductively coupled plasma. It has been shown that increase in body weight is accompanied by elevated hair cadmium content in women. At the same time, no significant alteration of hair cadmium concentration was observed in males. Higher values of scalp hair mercury and lead content were observed in men and women with increased body mass index independently of their age. BMI-related elevation of hair tin content was registered only in men of the first period of adulthood. A significant correlation between hair metal content and the values of BMI was observed for mercury independently of the gender of the subjects, whereas BMI values correlated significantly with hair cadmium levels in women and lead and tin levels in men. It has been also estimated that hair cadmium, mercury and lead levels in men exceed the respective values in women.

Interactions of iron with manganese, zinc, chromium, and selenium as related to prophylaxis and treatment of iron deficiency

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.

An essay on human and elements, multielement profiles, and depression

The recent development of the analytical techniques offers the unprecedented possibility to study simultaneously concentration of dozens of elements in the same biological matrix sample of 0.5–1.0 g (multielement profiles). The first part of this essay entitled “Think globally… An outline of trace elements in health and disease” aims to introduce the reader to the fascinating field of elements, there importance to our nutrition, their essentiality, deficiency, toxicity and bioavailability to the body and their overall role in health and disease, including the genetic metabolic impairments. In the second part of the essay entitled “… and act locally. The multielement profile of depression” we aimed to show the potential of such a hair multielement profile analysis for the study of human depression in a randomized, double blind, prospective, observational, cross-sectional, clinical, epidemiological, and analytical study. The preliminary results of this ongoing study lead us to put forward the hypothesis that the metabolic origin of depression may be due to some “energostat” failure, probably located in the thalamus, and activated by several essential element deficiencies.

Comparative angioprotective effects of magnesium compounds

Magnesium (Mg) deficiency is implicated in the development of numerous disorders of the cardiovascular system. Moreover, the data regarding the efficacy of different magnesium compounds in the correction of impaired functions due to low magnesium intake are often fragmentary and inconsistent. The aim of this study was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate, Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days. A low Mg diet decreased the Mg concentration in the plasma and erythrocytes, which was accompanied by a reduced concentration of eNOs and increased levels of endothelin-1 level in the serum and impaired endothelium-dependent vasodilatation. These effects increased the concentration of proinflammatory molecules, such as VCAM-1, TNF-α, IL-6 and CRP, indicating the development of systemic inflammation and endothelial dysfunction. The increased total NO level, which estimated from the sum of the nitrate and nitrite concentrations in the serum, may also be considered to be a proinflammatory marker. Two weeks of Mg supplementation partially or fully normalised the ability of the vascular wall to effect adequate endothelium-dependent vasodilatation and reversed the levels of most endothelial dysfunction and inflammatory markers (except CRP) to the mean values of the control group. Mg sulphate had the smallest effect on the endothelin-1, TNF-α and VCAM-1 levels. Mg N-acetyltaurate was significantly more effective in restoring the level of eNOS compared to all other studied compounds, except for Mg oxybutyrate. Taken together, the present findings demonstrate that all Mg compounds equally alleviate endothelial dysfunction and inflammation caused by Mg deficiency. Mg sulphate tended to be the least effective compound.

Relationship between selenium, lead, and mercury in red blood cells of Saudi autistic children

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can cause significant social, communication and behavioral challenges. Environmental contribution to ASD is due in large part to the sensitivity of the developing brain to external exposures such as lead (Pb), and mercury (Hg) as toxic heavy metals or due to a poor detoxification ability as the phenotype of this disorder. Selenium (Se) as an antioxidant element that counteracts the neurotoxicity of Hg, and Pb, presumably through the formation of nontoxic complexes. In the present study, Pb, Hg, and Se were measured in red blood cells (RBCs) of 35 children with ASD and 30 age- and gender-matched healthy control children using atomic absorption spectrometry. Receiver Operating Characteristics (ROC) analysis of the obtained data was performed to measure the predictive value of their absolute and relative concentrations. The obtained data demonstrates a significant elevation of Hg and Pb together with a significant decrease in the Se levels in RBCs of patients with ASD when compared to the healthy controls. The ratios of Se to both Pb and Hg were remarkably altered, being indicative of heavy metal neurotoxicity in patients with ASD. In conclusion, the present study indicates the importance of Se for prevention and/or therapy of heavy metal neurotoxicity.