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International Journal of Molecular... May 2020This study aims to investigate the cardiac electrical remodeling associated with intoxication by methylmercury (MeHg). We evaluated the chronic effects of MeHg on in...
This study aims to investigate the cardiac electrical remodeling associated with intoxication by methylmercury (MeHg). We evaluated the chronic effects of MeHg on in vivo electrocardiograms and on ex vivo action potentials and depolarizing (I) and repolarizing (I) currents. The acute effect of MeHg was evaluated on HEK293 cells expressing human ERG, Kv4.3 and KCNQ1/KCNE1 channels. Chronic MeHg treatment increased QTc and T-T interval duration, prolonged action potential duration and decreased amplitude of I and I. In addition, heterologously expressed I, I or I decreased after acute exposure to MeHg at subnanomolar range. The introduction of the in vitro effects of MeHg in a computer model of human ventricular action potentials triggered early afterdepolarizations and arrhythmia. In conclusion, cardiac electrical remodeling induced by MeHg poisoning is related to the reduction of I and I. The acute effect of MeHg on hKv4.3; hERG and hKCNQ1/KCNE1 currents and their transposition to in silico models show an association between MeHg intoxication and acquired Long QT Syndrome in humans. MeHg can exert its high toxicity either after chronic or acute exposure to concentrations as low as picomolar.
Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Atrial Remodeling; Calcium Channels; Computer Simulation; Disease Susceptibility; Electrophysiological Phenomena; HEK293 Cells; Heart Ventricles; Humans; Male; Methylmercury Compounds; Models, Cardiovascular; Potassium Channels; Rats, Wistar; Weight Loss
PubMed: 32429059
DOI: 10.3390/ijms21103490 -
Diagnostics (Basel, Switzerland) Jul 2021To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication.
PURPOSE
To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication.
DESIGN
Cross-sectional study.
PARTICIPANTS
Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects.
METHODS
The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM).
RESULTS
Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (<7 s) in 22.7% of patients. Schirmer test and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal esthesiometry showed patient mechanical (mean 147.81 (53.36) mL/min) and thermal thresholds to heat (+2.35 (+1.10) °C) and cold (-2.57 (-1.24) °C) to be significantly higher than controls. Corneal IVCM revealed lower values for nerve density (6.4 (2.94) n/mm), nerve branching density (2 (2.50) n/mm), and dendritic cell density (9.1 (8.84) n/mm) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels.
CONCLUSIONS
Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.
PubMed: 34441261
DOI: 10.3390/diagnostics11081326 -
Folia Medica Oct 2021Very few studies have evaluated the association between mercury exposure and oxidative stress in humans, particularly in children.
INTRODUCTION
Very few studies have evaluated the association between mercury exposure and oxidative stress in humans, particularly in children.
AIM
This is the first report where we aimed to determine the oxidative stress status of children who were accidentally exposed to elemental mercury.
MATERIALS AND METHODS
In the present study, the study group was composed of 86 randomly selected children poisoned by mercury; the control group was composed of 78 children who had no history of mercury exposure. At admission, blood samples were collected. Blood superoxide dismutase activity, catalase enzyme activity, and glutathione peroxidase activity were measured by Fridovich, Beutler, and Lawrence Burk methods respectively, and the results were given as U/g Hb. Malondialdehyde level was measured by Ohkawa methods, and the results were given as mmol/ml.
RESULTS
Catalase activity was significantly lower in the patient group compared to the control group (1.28±0.62 vs. 3.90±0.86 U/g Hb, p=0.010). In exposed children, SOD activity was significantly higher than the controls (5936±810 vs. 2226±464 U/g Hb, p=0.03), while the GSH-Px activity was significantly lower (13.01±3.21 vs. 34.97±7.32 U/g Hb, p=0.013). The MDA levels of the mercury group were significantly higher than the MDA levels of the control group (2.85±0.84 vs. 2.05±0.79 mmol/ml, p=0.04).
CONCLUSIONS
The results of the present study showed that acute mercury poisoning causes an alteration of oxidative stress status in children exposed to elemental mercury.
Topics: Antioxidants; Biomarkers; Catalase; Child; Humans; Mercury; Oxidative Stress; Superoxide Dismutase
PubMed: 35851205
DOI: 10.3897/folmed.63.e56110 -
Biology Sep 2021The aim of this review is to comprehensively present disorders of the reproductive system in cattle exposed to contact with toxic metals. Toxic metals are a common... (Review)
Review
The aim of this review is to comprehensively present disorders of the reproductive system in cattle exposed to contact with toxic metals. Toxic metals are a common environmental pollutant and can come from mines, smelters, fossil fuel combustion, or volcanic eruptions. Metals have the ability to bioaccumulate in living organisms, thus contaminating the food chain and may pose a threat to humans. They accumulate mainly in the liver and kidneys, but also in muscles and fat tissue. Toxic metals such as lead (Pb), arsenic (As), mercury (Hg), and cadmium (Cd) have a negative impact on the fertility of animals; they can lead to abortions, premature calving, or oocyte dysfunction. Moreover, in the male reproductive system, they disrupt spermatogenesis, and cause apoptosis of sperm and oxidative damage. The main source of exposure of livestock to toxic metals is through the consumption of feed or contaminated water. It is important to monitor the level of heavy metals in animal products to prevent human poisoning. Toxic metal biomonitoring can be performed by testing urine, blood, milk, plasma, or hair. Chromium (Cr), arsenic (As), and cadmium (Cd) are excreted in the urine, while lead can be detected by examining the blood of animals, while in milk, arsenic (As), cadmium (Cd), nickel (Ni), and lead (Pb) can be detected. Moreover, toxic metals do not biodegrade in the environment. To purify soil and waters, remediation methods, e.g., biological or chemical, should be used.
PubMed: 34571759
DOI: 10.3390/biology10090882 -
Bioorganic & Medicinal Chemistry Aug 2021The indole side chain of tryptophan is a versatile π-donor that can participate in various types of cation-π interactions. An understanding of how it may contribute as...
The indole side chain of tryptophan is a versatile π-donor that can participate in various types of cation-π interactions. An understanding of how it may contribute as an auxiliary binding group in mercury(II) complexes can provide valuable insights toward the design of effective chelators for optimal mercury immobilization. In this study, we investigate how the incorporation of two tryptophan residues in model dicysteinyl peptides might participate in peptide-mercury(II) complex stabilization. Two pentapeptides consisting of a Cys-Trp-Cys sequence motif containing a second tryptophan residue at the N-terminal (BT1) or C-terminal (BT2) were designed. An analogous cyclohexapeptide (BT3) was included to evaluate how tryptophan residues, restricted in constrained peptidic turn motifs, might take part in mercury(II) complexation. Their interactions with mercury(II) were investigated by spectroscopic methods and computational modeling. UV-vis studies indicate the formation of 1:1 dithiolated mercury(II) complex, which is corroborated by ESI-MS analysis. Spectroscopic studies reveal that the tryptophan indole group(s) in BT1 and BT3 can participate in mercury(II) cation-π interactions. Optimized 1:1 mercury(II)-BT3 structures indicate that both indole rings are very close to the mercury(II) coordination site and could stabilize it by shielding it from ligand exchange. These findings provide some useful insights toward use of aromatic donor groups as hydrophobic shields in designing more effective metal chelating agents.
Topics: Binding Sites; Mercury; Molecular Structure; Peptides; Spectrometry, Fluorescence; Sulfhydryl Compounds; Tryptophan
PubMed: 34237490
DOI: 10.1016/j.bmc.2021.116296 -
Animal Reproduction Science Sep 2022During the last decade, environmental toxicants have been considered a potential cause for declining sperm quality. Toxic metals are not easily degraded and may... (Meta-Analysis)
Meta-Analysis Review
During the last decade, environmental toxicants have been considered a potential cause for declining sperm quality. Toxic metals are not easily degraded and may accumulate along the food chain, which may negatively impact the semen quality of animals. In this framework, we conducted a meta-analysis to determine whether exposure to Al, As, Cd, Cr, Co, Cu, Fe, Mg, Mn, Hg, Ni, and Pb affects sperm and andrological parameters of domestic ruminants. We extracted 217 independent comparisons from 39 published articles selected from PubMed, Web of Science, and Scopus. Our findings showed that metal exposure reduced sperm viability (d = - 1.04, df 51, CI - 1.47 to - 0.61) and motility (d = - 0.83, df 104, CI -1.19 to - 0.51) by increasing oxidative metabolites production (d = 2.98, df 20, CI 1.95-0.11). Sperm viability and motility were affected by Cd, As, Hg, and Fe contamination. Metal poisoning impaired andrological parameters (d = - 0.83, df 17, CI - 1.10 to - 0.02) after arsenic intake using 3 and 5 mg L orally. Detrimental effects on spermatozoa were mostly observed after in vitro incubation with metals using concentrations < 2.99 mg L up to 24 h. The review limitations were the heterogeneity of methodologies used in the studies and absence of investigations focused on the effect of Al, Co, Cr, Mg, and Ni exposure on sperm parameters in ruminants. Nevertheless, our findings contribute to understanding the impact of metal exposure on reproductive parameters in ruminants, with potential damage to their fertility.
Topics: Animals; Cadmium; Male; Mercury; Ruminants; Semen; Semen Analysis; Spermatozoa
PubMed: 35930938
DOI: 10.1016/j.anireprosci.2022.107050 -
Environmental Science and Pollution... Jan 2022High blood mercury levels could lead to mercury poisoning, undoubtedly causing great harm to human health. However, the impact of the normal concentration of blood...
High blood mercury levels could lead to mercury poisoning, undoubtedly causing great harm to human health. However, the impact of the normal concentration of blood mercury on bone mineral density (BMD) is unclear. Therefore, this study explored the relationship between blood mercury levels and BMD and determined whether the relationship between blood mercury and BMD differs by populations. Two researchers extracted data from the 2005-2010 National Health and Nutrition Examination Survey database. Multivariate linear regression models were performed to evaluate the relationship between mercury level and BMD of the femoral regions and spine. Subgroup analysis was used to estimate differences according to population subgroups. Moreover, the nonlinear relationship of blood mercury levels and BMD was assessed using smooth curve fitting and generalized additive models. The results showed increased BMD with increasing mercury levels by multivariable-adjusted linear regression models, especially in the femoral regions. Subgroup analysis showed that the relationship was more likely to be present in non-Hispanic Whites, while a negative correlation between blood mercury levels and spinal BMD was observed in non-Hispanic Blacks. Furthermore, males (aged 20 to 29 years) and females (aged 30 to 39 years) with low blood mercury levels (< 3 ug/L) had increased risks of osteopenia or osteoporosis. This study showed that blood mercury level within the normal reference value of 10 μg/dL may be associated with BMD, especially with a lower blood mercury level, which may suggest an elevated risk of osteopenia or osteoporosis. However, causation could not be established due to the study design.
Topics: Bone Density; Cross-Sectional Studies; Female; Humans; Male; Mercury; Nutrition Surveys; Reference Values
PubMed: 34480303
DOI: 10.1007/s11356-021-16162-w -
Archives of Toxicology Jul 2021Metal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of... (Review)
Review
Metal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of literature has demonstrated that metal exposure may affect SIRT signaling, although the existing data are insufficient. Therefore, in this review we discuss the available data (PubMed-Medline, Google Scholar) on the influence of metal overload on sirtuin (SIRT) signaling and its association with other mechanisms involved in metal-induced toxicity. The existing data demonstrate that cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb), aluminium (Al), hexavalent chromium (Cr), manganese (Mn), iron (Fe), and copper (Cu) can inhibit SIRT1 activity. In addition, an inhibitory effect of Cd, Pb, As, and Fe on SIRT3 has been demonstrated. In turn, metal-induced inhibition of SIRT was shown to affect deacetylation of target proteins including FOXO, PGC1α, p53 and NF-kB. Increased acetylation downregulates PGC1α signaling pathway, resulting in cellular altered redox status and increased susceptibility to oxidative stress, as well as decreased mitochondrial biogenesis. Lower rates of LKB1 deacetylation may be responsible for metal-induced decreases in AMPK activity and subsequent metabolic disturbances. A shift to the acetylated FOXO results in increased expression of pro-apoptotic genes which upregulates apoptosis together with increased p53 signaling. Correspondingly, decreased NF-kB deacetylation results in upregulation of target genes of proinflammatory cytokines, enzymes, and cellular adhesion molecules thus promoting inflammation. Therefore, alterations in sirtuin activity may at least partially mediate metal-induced metabolic disturbances that have been implicated in neurotoxicity, nephrotoxicity, cardiotoxicity, and other toxic effects of heavy metals.
Topics: Cadmium; Heavy Metal Poisoning; Humans; Mercury; Metals, Heavy; Protective Agents; Sirtuins
PubMed: 34028595
DOI: 10.1007/s00204-021-03048-6 -
Current Pharmaceutical Design 2020Heavy metals are elements that are naturally found in the earth. They are used in many modern-day applications in agriculture, medicine, and industry. Heavy metal... (Review)
Review
BACKGROUND
Heavy metals are elements that are naturally found in the earth. They are used in many modern-day applications in agriculture, medicine, and industry. Heavy metal poisoning occurs when the body's soft tissues absorb too much of a particular metal. The heavy metals of interest for this review paper were cadmium, arsenic, mercury, and lead since these are the most common metals that the human body can absorb in toxic amounts. Different plant species were investigated in recent years for their effect on oxidative stress parameters after intoxication with heavy metals.
OBJECTIVES
This review paper is focused on the current update to research on heavy metals induced oxidative stress in animal models and improvement of the oxidative stress parameters upon/co-/after treatment with different plant extracts and isolated compounds.
METHODS
The available literature was screened for the novel data regarding the influence of plant extracts and compounds on heavy metals induced oxidative stress. For that purposes Scopus database was used, looking for the publications in the last 5-10 years with the key terms: plant extracts, oxidative stress, in vivo, cadmium, lead, mercury and arcenic.
RESULTS
Various parameters of oxidative stress were investigated, and their improvement with plant extracts/ compounds was observed in the brain, lungs, kidneys, liver, uterus, testis, thymus, spleen, heart, skin and blood of experimental animals. Common parameters used to determine oxidative stress in animals were: superoxide dismutase; catalase; reduced glutathione; glutathione reductase; glutathione-S-transferase; glutathione peroxidase; lipid peroxidation; oxidized glutathione; malondialdehyde; xanthine oxidase; nonprotein-soluble thiol; thioredoxin reductase; total sulphydryl group; nitric oxide; γ-glutamyl cysteine synthetase.
CONCLUSION
The most investigated species for antioxidant effects upon intoxication with heavy metals seem to be Allium sp., Bacopa monniera, Camellia sinensis, Moringa oleifera, Vitis vinifera and Zingiber officinale. According to literature data, the most promising effect to alleviate symptoms of intoxication was achieved with proanthocyanidins obtained from Vitis vinifera.
Topics: Animals; Antioxidants; Catalase; Glutathione; Glutathione Reductase; Humans; Male; Metals, Heavy; Oxidative Stress; Plant Extracts
PubMed: 32264808
DOI: 10.2174/1381612826666200407163408 -
JAMA Network Open Mar 2020The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown.
IMPORTANCE
The balance of mercury risk and nutritional benefit from fish intake during pregnancy for the metabolic health of offspring to date is unknown.
OBJECTIVE
To assess the associations of fish intake and mercury exposure during pregnancy with metabolic syndrome in children and alterations in biomarkers of inflammation in children.
DESIGN, SETTING, AND PARTICIPANTS
This population-based prospective birth cohort study used data from studies performed in 5 European countries (France, Greece, Norway, Spain, and the UK) between April 1, 2003, and February 26, 2016, as part of the Human Early Life Exposome (HELIX) project. Mothers and their singleton offspring were followed up until the children were aged 6 to 12 years. Data were analyzed between March 1 and August 2, 2019.
EXPOSURES
Maternal fish intake during pregnancy (measured in times per week) was assessed using validated food frequency questionnaires, and maternal mercury concentration (measured in micrograms per liter) was assessed using maternal whole blood and cord blood samples.
MAIN OUTCOMES AND MEASURES
An aggregate metabolic syndrome score for children was calculated using the z scores of waist circumference, systolic and diastolic blood pressures, and levels of triglyceride, high-density lipoprotein cholesterol, and insulin. A higher metabolic syndrome score (score range, -4.9 to 7.5) indicated a poorer metabolic profile. Three protein panels were used to measure several cytokines and adipokines in the plasma of children.
RESULTS
The study included 805 mothers and their singleton children. Among mothers, the mean (SD) age at cohort inclusion or delivery of their infant was 31.3 (4.6) years. A total of 400 women (49.7%) had a high educational level, and 432 women (53.7%) were multiparous. Among children, the mean (SD) age was 8.4 (1.5) years (age range, 6-12 years). A total of 453 children (56.3%) were boys, and 734 children (91.2%) were of white race/ethnicity. Fish intake consistent with health recommendations (1 to 3 times per week) during pregnancy was associated with a 1-U decrease in metabolic syndrome score in children (β = -0.96; 95% CI, -1.49 to -0.42) compared with low fish consumption (<1 time per week) after adjusting for maternal mercury levels and other covariates. No further benefit was observed with fish intake of more than 3 times per week. A higher maternal mercury concentration was independently associated with an increase in the metabolic syndrome score of their offspring (β per 2-fold increase in mercury concentration = 0.18; 95% CI, 0.01-0.34). Compared with low fish intake, moderate and high fish intake during pregnancy were associated with reduced levels of proinflammatory cytokines and adipokines in children. An integrated analysis identified a cluster of children with increased susceptibility to metabolic disease, which was characterized by low fish consumption during pregnancy, high maternal mercury levels, decreased levels of adiponectin in children, and increased levels of leptin, tumor necrosis factor α, and the cytokines interleukin 6 and interleukin 1β in children.
CONCLUSIONS AND RELEVANCE
Results of this study suggest that moderate fish intake consistent with current health recommendations during pregnancy was associated with improvements in the metabolic health of children, while high maternal mercury exposure was associated with an unfavorable metabolic profile in children.
Topics: Adult; Animals; Biomarkers; Child; Female; Fishes; Humans; Incidence; Inflammation; Maternal Exposure; Mercury; Mercury Poisoning; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Factors; United States
PubMed: 32176304
DOI: 10.1001/jamanetworkopen.2020.1007