The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPAR and C/EBP); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPARγ and C/EBPα); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.publishedVersio

From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles

Titanium dioxide nanoparticles (TiO2NPs) are widely produced and used nanoparticles. Yet, TiO2NP exposure may possess toxic effects to different cells and tissues, including the brain. Recent studies significantly expanded the understanding of the molecular mechanisms underlying TiO2NP neurotoxicity implicating a number of both direct and indirect mechanisms. In view of the significant recent progress in research on TiO2NP neurotoxicity, the objective of the present study is to provide a narrative review on the molecular mechanisms involved in its neurotoxicity, with a special focus on the studies published in the last decade. The existing data demosntrate that although TiO2NP may cross blood-brain barrier and accumulate in brain, its neurotoxic effects may be mediated by systemic toxicity. In addition to neuronal damage and impaired neurogenesis, TiO2NP exposure also results in reduced neurite outgrowth and impaired neurotransmitter metabolism, especially dopamine and glutamate. TiO2NP exposure was also shown to promote α-synuclein and β-amyloid aggregation, thus increasing its toxicity. Recent findings also suggest that epigenetic effects and alterations in gut microbiota biodiversity contribute to TiO2NP neurotoxicity. Correspondingly, in vivo studies demosntrated that TiO2NPs induce a wide spectrum of adverse neurobehavioral effects, while epidemiological data are lacking. In addition, TiO2NPs were shown to promote neurotoxic effects of other toxic compounds. Here we show the contribution of a wide spectrum of molecular mechanisms to TiO2NP-induced neurotoxicity; yet, the role of TiO2NP exposure in adverse neurological outcomes in humans has yet to be fully appreciated

The Impact of Maternal Overweight on Hair Essential Trace Element and Mineral Content in Pregnant Women and Their Children

The aim of the present study was to investigate hair essential trace elements and mineral levels in 105 pregnant normal-weight (control) and 55 overweight and obese women in the third trimester of pregnancy, as well as in their children at the age of 9 months. The hair essential trace elements and mineral levels were assessed using inductively coupled plasma mass-spectrometry. Overweight pregnant women had significantly reduced Cr (- 24%; p = 0.047) and Zn (- 13%; p = 0.008) content, as well as elevated hair Na and K levels as compared to the controls. Children from overweight and obese mothers had lower hair Mo (- 18%; p = 0.017), Se (- 8%; p = 0.043), and V (- 24%; p = 0.028) levels, as well as elevated Sr content (19%; p = 0.025). Correlation analysis revealed a significant relationship between maternal and child hair levels of Co (r = 0.170; p = 0.038), Cu (r = 0.513; p < 0.001), Mn (r = 0.240; p = 0.003), and Na (r = 0.181; p = 0.027) in the whole sample. Pre-pregnancy maternal body mass index (BMI) positively correlated with maternal hair K (r = 0.336; p < 0.001) and Na (r = 0.212; p = 0.008) and negatively correlated with V (r = - 0.204; p = 0.011) and Zn (r = - 0.162; p = 0.045) levels. The results indicate that impaired trace element and mineral metabolism may play a role in the link between maternal obesity, complications of pregnancy and child's postnatal development. Hypothetically, dietary improvement may be used as a tool to reduce these risks. However, further experimental and clinical studies are required to investigate the relationship between obesity and trace element metabolism in pregnancy

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. Keywords: Apoptosis; Conjugates; Cysteine; Mercury; S-mercuration.R01 ES007331/ES/NIEHS NIH HHS/United States R01 ES010563/ES/NIEHS NIH HHS/United States R01 ES020852/ES/NIEHS NIH HHS/United StatesacceptedVersio

The impact of lifestyle factors on age-related differences in hair trace element content in pregnant women in the third trimester

BACKGROUND: Trace elements play a significant role in the regulation of human reproduction, while advanced age may have a significant impact on trace element metabolism. The objective of the present study was to assess the impact of lifestyle factors on age-related differences in hair trace element content in pregnant women in the third trimester. METHODS: A total of 124 pregnant women aged 20&ndash;29 (n = 72) and 30&ndash;39 (n = 52) were ex- amined. Scalp hair trace element content was assessed using inductively coupled plasma mass spectrometry at NexION 300D (Perkin Elmer, USA) after microwave digestion. RESULTS: The results showed that the elder pregnant women had 36% (p = 0.009), 14% (p = 0.045), and 45% (p = 0.044) lower hair Zn, V, and Cd content, and 16% (p = 0.044) higher hair B levels &ndash; in comparison to the respective younger group values. Multiple regression analysis demonstrated that the age of the women had a significant influence on hair V and Zn levels. B content was also significantly influenced by age at first intercourse, smoking status, and specific dietary habits. None of the lifestyle factors were associated with hair Cd content in pregnant women. Hair V levels were also affected by following a special diet. Interestingly, alcohol intake did not have a significant impact on hair trace element content. CONCLUSIONS: These data indicate that lifestyle factors have a significant influence on age-related changes in hair trace elements during pregnancy that may impact the outcome of pregnancy

Toxicological and nutritional status of trace elements in hair of women with in vitro fertilization (IVF) pregnancy and their 9-month-old children

The objective of the present study was to assess toxic and nutritional trace element and mineral status in hair of women with IVF pregnancy and their children. Inductively-coupled plasma mass-spectrometry was used to as-sess hair trace element levels of 50 women with IVF pregnancy and 158 controls with spontaneous pregnancy and their children. Women with IVF pregnancy were characterized by significantly elevated hair As, Hg, Li, K, Na, and reduced Fe, Si, and Zn contents. Children from IVF pregnancy had significantly lower values of hair Cr, Fe, Mg, Sr, and Al content when compared to the control values, whereas hair Hg and Mo levels were higher. Hair trace element levels were associated with pregnancy complications and infertility, but not newborn characteristics. The results suggest the need for preconceptional monitoring and correction of the levels of toxic and essential elements in women in order to improve the course pregnancy and child development

Hair Trace Element and Electrolyte Content in Women with Natural and In Vitro Fertilization-Induced Pregnancy

The objective of the present study was to perform comparative analysis of hair trace element content in women with natural and in vitro fertilization (IVF)-induced pregnancy. Hair trace element content in 33 women with IVF-induced pregnancy and 99 age- and body mass index-matched control pregnant women (natural pregnancy) was assessed using inductively coupled plasma mass spectrometry. The results demonstrated that IVF-pregnant women are characterized by significantly lower hair levels of Cu, Fe, Si, Zn, Ca, Mg, and Ba at p < 0.05 or lower. Comparison of the individual levels with the national reference values demonstrated higher incidence of Fe and Cu deficiency in IVF-pregnant women in comparison to that of the controls. IVF pregnancy was also associated with higher hair As levels (p < 0.05). Multiple regression analysis revealed a significant interrelation between IVF pregnancy and hair Cu, Fe, Si, and As content. Hair Cu levels were also influenced by vitamin/mineral supplementation and the number of pregnancies, whereas hair Zn content was dependent on prepregnancy anthropometric parameters. In turn, planning of pregnancy had a significant impact on Mg levels in scalp hair. Generally, the obtained data demonstrate an elevated risk of copper, iron, zinc, calcium, and magnesium deficiency and arsenic overload in women with IVF-induced pregnancy. The obtained data indicate the necessity of regular monitoring of micronutrient status in IVF-pregnant women in order to prevent potential deleterious effects of altered mineral homeostasis

Serum zinc, copper, and other biometals are associated with covid-19 severity markers

The objective of the present study was to evaluate of serum metal levels in COVID-19 patients with different disease severity, and to investigate the independent association between serum metal profile and markers of lung damage. The cohort of COVID-19 patients consisted of groups of subjects with mild, moderate, and severe illness, 50 examinees each. Forty-four healthy subjects of the respective age were involved in the current study as the control group. Serum metal levels were evaluated using inductively-coupled plasma mass-spectrometry. Examination of COVID-19 patients demonstrated that heart rate, respiratory rate, body temperature, C-reactive protein levels, as well as lung damage increased significantly with COVID-19 severity, whereas SpO decreased gradually. Increasing COVID-19 severity was also associated with a significant gradual decrease in serum Ca, Fe, Se, Zn levels as compared to controls, whereas serum Cu and especially Cu/Zn ratio were elevated. No significant group differences in serum Mg and Mn levels were observed. Serum Ca, Fe, Se, Zn correlated positively with SpO , being inversely associated with fever, lung damage, and C-reactive protein concentrations. Opposite correlations were observed for Cu and Cu/Zn ratio. In regression models, serum Se levels were inversely associated with lung damage independently of other markers of disease severity, anthropometric, biochemical, and hemostatic parameters. Cu/Zn ratio was also considered as a significant predictor of lower SpO in adjusted regression models. Taken together, these findings demonstrated that metal metabolism significantly interferes with COVID-19 pathogenesis, although the causal relations as well as precise mechanisms are yet to be characterized. 2 2

Essential trace elements in neurodevelopment: An updated narrative

Over the past 50 years, our understanding of the role of trace elements in animals and humans has significantly expanded. Some elements have been recognized as essential for vital body functions. Since the 1950s, with advances in histochemical and spectrometric methods, the distribution of trace elements in different structures of the brain has been studied. Scientific knowledge about the effects of trace elements on brain function has accumulated tremendously as well. Essential trace elements are considered as micronutrients, which are not produced in the body and mainly come from food. Different brain regions such as the cortex, white matter, basal ganglia, and the limbic system have various developmental trajectories and the so-called “critical periods.” The correctness of development is determined by the course of various processes (proliferation, migration, myelination, differentiation, etc.). Thus, it could be assumed that an imbalance of essential trace elements in critical periods of brain maturation can lead to detrimental morphofunctional consequences and impaired brain development. In this chapter, we have reviewed the most studied trace elements that are involved in neurogenesis, such as Fe, Zn, I, Se, Cu, and Mn, and their possible contribution to the manifestation of neurological disorders