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

PREVENTIVE ZINC SUPPLEMENTATION EFFECT ON REDOX STATUS IN RAT MODEL OF MAFLD

Background. Oxidative stress plays an important role in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). Antioxidant trace elements as cofactors of antioxidant enzymes and metalloproteins are involved in this process. Zinc being an important antioxidant may have a positive effect on the treatment of liver pathology. The study aimed to assess the effect of preventive zinc supplementation on MAFLD in rats. Materials and Methods. A total of 26 three-month-old female Wistar rats were used in the present study. The activity of the antioxidant enzymes superoxide dismutase and catalase, some redox status markers, such as ceruloplasmin, oxidized tryptophan, dithyrosines, total thiols, carbonyls, TBARS, and uric acid were evaluated. Oxidative stress biomarkers were studied spectrophotometrically. Results. MAFLD was accompanied by hyperuricemia and a decrease in serum dityrosines. The addition of Zn to the diet prevented the development of steatosis, decreased the level of oxidized tryptophan in the liver, and paradoxically caused hyperuricemia in the MAFLD model used. Zn supplementation had a positive effect on the prevention of MAFLD, had a little effect on redox status of animals but caused paradoxical hyperuricemia. Future studies are needed to establish the mechanisms of the Zn effect at the cellular level

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

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

Thallium-induced DNA damage, genetic, and epigenetic alterations

Thallium (Tl) is a toxic heavy metal responsible for noxious effects in living organisms. As a pollutant, Tl can be found in the environment at high concentrations, especially in industrial areas. Systemic toxicity induced by this toxic metal can affect cell metabolism, including redox alterations, mitochondrial dysfunction, and activation of apoptotic signaling pathways. Recent focus on Tl toxicity has been devoted to the characterization of its effects at the nuclear level, with emphasis on DNA, which, in turn, may be responsible for cytogenetic damage, mutations, and epigenetic changes. In this work, we review and discuss past and recent evidence on the toxic effects of Tl at the systemic level and its effects on DNA. We also address Tl’s role in cancer and its control

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

Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update

Understanding of the immediate mechanisms of Mn-induced neurotoxicity is rapidly evolving. We seek to provide a summary of recent findings in the field, with an emphasis to clarify existing gaps and future research directions. We provide, here, a brief review of pertinent discoveries related to Mn-induced neurotoxicity research from the last five years. Significant progress was achieved in understanding the role of Mn transporters, such as SLC39A14, SLC39A8, and SLC30A10, in the regulation of systemic and brain manganese handling. Genetic analysis identified multiple metabolic pathways that could be considered as Mn neurotoxicity targets, including oxidative stress, endoplasmic reticulum stress, apoptosis, neuroinflammation, cell signaling pathways, and interference with neurotransmitter metabolism, to name a few. Recent findings have also demonstrated the impact of Mn exposure on transcriptional regulation of these pathways. There is a significant role of autophagy as a protective mechanism against cytotoxic Mn neurotoxicity, yet also a role for Mn to induce autophagic flux itself and autophagic dysfunction under conditions of decreased Mn bioavailability. This ambivalent role may be at the crossroad of mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis. Yet very recent evidence suggests Mn can have toxic impacts below the no observed adverse effect of Mn-induced mitochondrial dysfunction. The impact of Mn exposure on supramolecular complexes SNARE and NLRP3 inflammasome greatly contributes to Mn-induced synaptic dysfunction and neuroinflammation, respectively. The aforementioned effects might be at least partially mediated by the impact of Mn on α-synuclein accumulation. In addition to Mn-induced synaptic dysfunction, impaired neurotransmission is shown to be mediated by the effects of Mn on neurotransmitter systems and their complex interplay. Although multiple novel mechanisms have been highlighted, additional studies are required to identify the critical targets of Mn-induced neurotoxicity