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Diabetes Care Nov 2013Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively...
OBJECTIVE
Emerging in vitro and animal evidence suggests that methylmercury could increase type 2 diabetes, but little evidence exists in humans. We aimed to prospectively determine associations of mercury exposure, as assessed by biomarker measurement, with incident diabetes.
RESEARCH DESIGN AND METHODS
We used neutron activation analysis to measure toenail mercury, an objective biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline in two separate U.S. prospective cohorts. Incident diabetes was identified from biennial questionnaires and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Associations of mercury exposure with incident diabetes were assessed using Cox proportional hazards.
RESULTS
During mean ± SD follow-up of 19.7 ± 7.0 years, 1,010 new cases of diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 μg/g in men and 0.76 μg/g in women, corresponding to exposures ∼3.5-fold and 2-fold higher than the U.S. Environmental Protection Agency reference dose. In multivariable analyses, toenail mercury concentrations were not associated with higher incidence of diabetes in women, men, or both cohorts combined. Comparing the highest to lowest quintile of exposure, the hazard ratio (95% CI) for incident diabetes was 0.86 (0.66-1.11) in women, 0.69 (0.42-1.15) in men, and 0.77 (0.61-0.98) in the combined cohorts. Findings were similar when more extreme categories (deciles) of mercury were compared, and in analyses stratified by fish or omega-3 consumption, BMI, and age.
CONCLUSIONS
These findings from two separate large prospective cohorts do not support adverse effects of methylmercury on development of diabetes in men or women at usual levels of exposure seen in these populations.
Topics: Adult; Aged; Animals; Diabetes Mellitus, Type 2; Environmental Exposure; Fatty Acids, Omega-3; Female; Fishes; Humans; Incidence; Male; Methylmercury Compounds; Middle Aged; Nails; Prospective Studies; United States; United States Environmental Protection Agency
PubMed: 24026556
DOI: 10.2337/dc13-0894 -
Biological Trace Element Research 2008Thyroid hormones are essential for cellular metabolism, growth, and development. In particular, an adequate supply of thyroid hormones is critical for fetal... (Review)
Review
Thyroid hormones are essential for cellular metabolism, growth, and development. In particular, an adequate supply of thyroid hormones is critical for fetal neurodevelopment. Thyroid hormone tissue activation and inactivation in brain, liver, and other tissues is controlled by the deiodinases through the removal of iodine atoms. Selenium, an essential element critical for deiodinase activity, is sensitive to mercury and, therefore, when its availability is reduced, brain development might be altered. This review addresses the possibility that high exposures to the organometal, methylmercury (MeHg), may perturb neurodevelopmental processes by selectively affecting thyroid hormone homeostasis and function.
Topics: Enzyme Activation; Humans; Iodide Peroxidase; Methylmercury Compounds; Selenium; Thyroid Hormones
PubMed: 18716716
DOI: 10.1007/s12011-008-8199-3 -
Nihon Eiseigaku Zasshi. Japanese... Sep 2011More than fifty years have passed since the outbreak of Minamata disease, and large-scale methylmercury poisoning due to industrial effluents or methylmercury-containing... (Review)
Review
More than fifty years have passed since the outbreak of Minamata disease, and large-scale methylmercury poisoning due to industrial effluents or methylmercury-containing fungicide intoxication has scarcely happened in developed countries. On the other hand, widespread environmental mercury contamination has occurred in gold and mercury mining areas of developing countries. In this article, we provided an overview of recent studies addressing human health effects of methylmercury, which we searched using the PubMed of the US National Library of Medicine. The following suggestions were obtained for low-level methylmercury exposure: (1) In recent years, the proportion of human studies addressing methylmercury has tended to decrease. (2) Prenatal exposure to methylmercury through fish intake, even at low levels, adversely affects child development after adjusting for polychlorinated biphenyls and maternal fish intake during pregnancy, whereas maternal seafood intake has some benefits. (3) Long-term methylmercury exposure through consumption of fish such as bigeye tuna and swordfish may pose a potential risk of cardiac events involving sympathovagal imbalance. (4) In measuring methylmercury levels in preserved umbilical cord collected from inhabitants born in Minamata areas between 1945 and 1989, the elevated concentrations (≥1 mg/g) were observed mainly in inhabitants born between 1947 and 1968, and the peak coincided with the peak of acetaldehyde production in Minamata. (5) Since some developing countries appear to be in similar situations to Japan in the past, attention should be directed toward early recognition of a risky agent and precautions should be taken against it.
Topics: Cardiovascular Diseases; Developing Countries; Female; Humans; Japan; Mercury Poisoning; Methylmercury Compounds; Pregnancy; Water Pollution, Chemical
PubMed: 21996768
DOI: 10.1265/jjh.66.682 -
International Journal of Environmental... Jan 2022This study measures total mercury (THg), methylmercury (MeHg) and selenium (Se) concentrations in elasmobranch fish from an Italian market with the aim of evaluating the...
This study measures total mercury (THg), methylmercury (MeHg) and selenium (Se) concentrations in elasmobranch fish from an Italian market with the aim of evaluating the risk-benefit associated with their consumption, using estimated weekly intake (EWI), permissible safety level (MeHg), selenium health benefit value (HBV) and monthly consumption rate limit (CR) for each species. THg and Se were analysed by atomic absorption spectrometry, while MeHg was determined by HrGc/Ms. THg and MeHg concentrations ranged from 0.61 to 1.25 μg g w.w. and from 0.57 to 0.97 μg g w.w., respectively, whereas Se levels were 0.49-0.65 μg g w.w. In most samples European Community limits for THg were surpassed, while for MeHg none of the fish had levels above the limit adopted by FAO/WHO. EWIs for THg and MeHg in many cases were above the provisional tolerable weekly intakes (PTWIs). MeHg estimate showed that fish should contain approximately 50% of the concentration measured to avoid exceeding the PTWI. Nevertheless, the HBV index indicated that solely skates were safe for human consumption (HBV = 3.57-6.22). Our results highlight the importance of a constant monitoring of THg and MeHg level in fish, especially in apex predators, to avoid the risk of overexposure for consumers.
Topics: Animals; Elasmobranchii; Environmental Monitoring; Fishes; Humans; Mercury; Methylmercury Compounds; Seafood; Selenium; Water Pollutants, Chemical
PubMed: 35055610
DOI: 10.3390/ijerph19020788 -
Environmental Health Perspectives Feb 2002The three modern "faces" of mercury are our perceptions of risk from the exposure of billions of people to methyl mercury in fish, mercury vapor from amalgam tooth... (Review)
Review
The three modern "faces" of mercury are our perceptions of risk from the exposure of billions of people to methyl mercury in fish, mercury vapor from amalgam tooth fillings, and ethyl mercury in the form of thimerosal added as an antiseptic to widely used vaccines. In this article I review human exposure to and the toxicology of each of these three species of mercury. Mechanisms of action are discussed where possible. Key gaps in our current knowledge are identified from the points of view both of risk assessment and of mechanisms of action.
Topics: Animals; Dental Amalgam; Environmental Exposure; Fishes; Food Contamination; Humans; Mercury; Methylmercury Compounds; Preservatives, Pharmaceutical; Risk Assessment; Thimerosal; Vaccines; Volatilization
PubMed: 11834460
DOI: 10.1289/ehp.02110s111 -
Applied and Environmental Microbiology Mar 2022The operon encodes enzymes that transform and detoxify methylmercury (MeHg) and/or inorganic mercury [Hg(II)]. Organomercurial lyase (MerB) and mercuric reductase...
The operon encodes enzymes that transform and detoxify methylmercury (MeHg) and/or inorganic mercury [Hg(II)]. Organomercurial lyase (MerB) and mercuric reductase (MerA) can act sequentially to demethylate MeHg to Hg(II) and reduce Hg(II) to volatile elemental mercury (Hg) that can escape from the cell, conferring resistance to MeHg and Hg(II). Most identified operons encode either MerA and MerB in tandem or MerA alone; however, microbial genomes were recently identified that encode only MerB. However, the effects of potentially producing intracellular Hg(II) via demethylation of MeHg by MerB, independent of a mechanism to further detoxify or sequester the metal, are not well understood. Here, we investigated MeHg biotransformation in Escherichia coli strains engineered to express MerA and MerB, together or separately, and characterized cell viability and Hg detoxification kinetics when these strains were grown in the presence of MeHg. Strains expressing only MerB are capable of demethylating MeHg to Hg(II). Compared to strains that express both MerA and MerB, strains expressing only MerB exhibit a lower MIC with MeHg exposure, which parallels a redistribution of Hg from the cell-associated fraction to the culture medium, consistent with cell lysis occurring. The data support a model whereby intracellular production of Hg(II), in the absence of reduction or other forms of demobilization, results in a greater cytotoxicity than the parent MeHg compound. Collectively, these results suggest that in the context of MeHg detoxification, MerB must be accompanied by an additional mechanism(s) to reduce, sequester, or redistribute generated Hg(II). Mercury is a globally distributed pollutant that poses a risk to wildlife and human health. The toxicity of mercury is influenced largely by microbially mediated biotransformation between its organic (methylmercury) and inorganic [Hg(II) and Hg] forms. Here, we show in a relevant cellular context that the organomercurial lyase (MerB) enzyme is capable of MeHg demethylation without subsequent mercuric reductase (MerA)-mediated reduction of Hg(II). Demethylation of MeHg without subsequent Hg(II) reduction results in a greater cytotoxicity and increased cell lysis. Microbes carrying MerB alone have recently been identified but have yet to be characterized. Our results demonstrate that operons encoding MerB but not MerA put the cell at a disadvantage in the context of MeHg exposure, unless subsequent mechanisms of reduction or Hg(II) sequestration exist. These findings may help uncover the existence of alternative mechanisms of Hg(II) detoxification in addition to revealing the drivers of operon evolution.
Topics: Demethylation; Humans; Lyases; Mercury; Methylmercury Compounds; Oxidoreductases
PubMed: 35138926
DOI: 10.1128/aem.00010-22 -
Human & Experimental Toxicology 2022Methylmercury (MeHg) is a neurotoxin that induces neurotoxicity and cell death in neurons. MeHg increases oligodendrocyte death, glial cell activation, and motor neuron...
Methylmercury (MeHg) is a neurotoxin that induces neurotoxicity and cell death in neurons. MeHg increases oligodendrocyte death, glial cell activation, and motor neuron demyelination in the motor cortex and spinal cord. As a result, MeHg plays an important role in developing neurocomplications similar to amyotrophic lateral sclerosis (ALS). Recent research has implicated c-JNK and p38MAPK overactivation in the pathogenesis of ALS. Apigenin (APG) is a flavonoid having anti-inflammatory, antioxidant, and c-JNK/p38MAPK inhibitory activities. The purpose of this study is to determine whether APG possesses neuroprotective effects in MeHg-induced neurotoxicity in adult rats associated with ALS-like neuropathological alterations. In the current study, the neurotoxin MeHg causes an ALS-like phenotype in Wistar rats after 21 days of oral administration at a dose of 5 mg/kg. Prolonged administration of APG (40 and 80 mg/kg) improved neurobehavioral parameters such as learning memory, cognition, motor coordination, and grip strength. This is mainly associated with the downregulation of c-JNK and p38MAPK signaling as well as the restoration of myelin basic protein within the brain. Furthermore, APG inhibited neuronal apoptotic markers (Bax, Bcl-2, and caspase-3), restored neurotransmitter imbalance, decreased inflammatory markers (TNF- and IL-1), and alleviated oxidative damage. As a result, the current study shows that APG has neuroprotective potential as a c-JNK and p38MAPK signaling inhibitor against MeHg-induced neurotoxicity in adult rats. Based on these promising findings, we suggested that APG could be a potential new therapeutic approach over other conventional therapeutic approaches for MeHg-induced neurotoxicity in neurobehavioral, molecular, and neurochemical abnormalities.
Topics: Animals; Apigenin; Methylmercury Compounds; Neurons; Neurotoxicity Syndromes; Rats; Rats, Wistar
PubMed: 35373622
DOI: 10.1177/09603271221084276 -
International Journal of Environmental... Jul 2015Methylmercury is well known for causing adverse health effects in the brain and nervous system. Estimating the elimination constant derived from the biological half-life...
Methylmercury is well known for causing adverse health effects in the brain and nervous system. Estimating the elimination constant derived from the biological half-life of methylmercury in the blood or hair is an important part of calculating guidelines for methylmercury intake. Thus, this study was conducted to estimate the biological half-life of methylmercury in Korean adults. We used a one-compartment model with a direct relationship between methylmercury concentrations in the blood and daily dietary intake of methylmercury. We quantified the between-person variability of the methylmercury half-life in the population, and informative priors were used to estimate the parameters in the model. The population half-life of methylmercury was estimated to be 80.2 ± 8.6 days. The population mean of the methylmercury half-life was 81.6 ± 8.4 days for men and 78.9 ± 8.6 days for women. The standard deviation of the half-life was estimated at 25.0 ± 8.6 days. Using the direct relationship between methylmercury concentrations in blood and methylmercury intake, the biological half-life in this study was estimated to be longer than indicated by the earlier studies that have been used to set guideline values.
Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Diet; Female; Half-Life; Humans; Male; Methylmercury Compounds; Middle Aged; Models, Theoretical; Republic of Korea; Toxicokinetics; Young Adult
PubMed: 26264017
DOI: 10.3390/ijerph120809054 -
Scientific Reports Mar 2019Methylmercury is an environmental pollutant that causes specific and serious damage to the central nervous system. We have previously shown that C-C motif chemokine...
Methylmercury is an environmental pollutant that causes specific and serious damage to the central nervous system. We have previously shown that C-C motif chemokine ligand 4 (CCL4) protects cultured neural cells from methylmercury toxicity and expression of CCL4 is specifically induced in mouse brain by methylmercury. In this study, we examined the transcriptional regulatory mechanism that induces CCL4 expression by methylmercury using C17.2 mouse neural stem cells. The promoter region of the CCL4 gene was analyzed by a reporter assay, revealing that the region up to 50 bp upstream from the transcription start site was necessary for inducing expression of CCL4 by methylmercury. Nine transcription factors that might bind to this upstream region and be involved in the induction of CCL4 expression by methylmercury were selected, and the induction of CCL4 expression by methylmercury was suppressed by the knockdown of serum response factor (SRF). In addition, the nuclear level of SRF was elevated by methylmercury, and an increase in the amount bound to the CCL4 gene promoter was also observed. Furthermore, we examined the upstream signaling pathway involved in the induction of CCL4 expression by SRF, and confirmed that activation of p38 and ERK, which are part of the MAPK pathway, are involved. These results suggest that methylmercury induces the expression of CCL4 by activating SRF via the p38 and ERK signaling pathway. Our findings are important for elucidating the mechanism involved in the brain-specific induction of CCL4 expression by methylmercury.
Topics: Animals; Brain; Cell Line; Cells, Cultured; Chemokine CCL4; Gene Expression Regulation; MAP Kinase Signaling System; Methylmercury Compounds; Mice; NF-kappa B; Neural Stem Cells; Promoter Regions, Genetic; Serum Response Factor; Signal Transduction; Transcription Factors
PubMed: 30874621
DOI: 10.1038/s41598-019-41127-y -
Chemico-biological Interactions Jan 2020Methylmercury (MeHg) and Ethylmercury (EtHg) are toxic to the central nervous system. Human exposure to MeHg and EtHg results mainly from the consumption of contaminated...
Methylmercury (MeHg) and Ethylmercury (EtHg) are toxic to the central nervous system. Human exposure to MeHg and EtHg results mainly from the consumption of contaminated fish and thimerosal-containing vaccines, respectively. The mechanisms underlying the toxicity of MeHg and EtHg are still elusive. Here, we compared the toxic effects of MeHg and EtHg in Saccharomyces cerevisiae (S. cerevisiae) emphasizing the involvement of oxidative stress and the identification of molecular targets from antioxidant pathways. Wild type and mutant strains with deleted genes for antioxidant defenses, namely: γ-glutamylcysteine synthetase, glutathione peroxidase, catalase, superoxide dismutase, mitochondrial peroxiredoxin, cytoplasmic thioredoxin, and redox transcription factor Yap1 were used to identify potential pathways and proteins from cell redox system targeted by MeHg and EtHg. MeHg and EtHg inhibited cell growth, decreased membrane integrity, and increased the granularity and production of reactive species (RS) in wild type yeast. The mutants were predominantly less tolerant of mercurial than wild type yeast. But, as the wild strain, mutants exhibited higher tolerance to MeHg than EtHg. Our results indicate the involvement of oxidative stress in the cytotoxicity of MeHg and EtHg and reinforce S. cerevisiae as a suitable model to explore the mechanisms of action of electrophilic toxicants.
Topics: Antioxidants; Ethylmercury Compounds; Methylmercury Compounds; Oxidation-Reduction; Oxidative Stress; Saccharomyces cerevisiae
PubMed: 31672467
DOI: 10.1016/j.cbi.2019.108867