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Environmental Health and Preventive... 2024The developing brains are sensitive to methylmercury (MeHg). However, the exposure to MeHg in baby foods and toddler meals remains unknown. This study aimed to determine...
BACKGROUND
The developing brains are sensitive to methylmercury (MeHg). However, the exposure to MeHg in baby foods and toddler meals remains unknown. This study aimed to determine MeHg intake from baby food or toddler meals, and to investigate the relationship with child hair total mercury (THg).
METHODS
A total of 3 days of 24-hour dietary diet and hair samples were collected from 260 consenting children aged 0-5 years. We measured the concentrations of THg and MeHg in the diet and THg in the hair.
RESULTS
The results of measuring THg were below both the method detection and method quantification limits or either of both in powdered milk (93.8%), 5-6 months (53.3%), and 7-8 months (39.5%). The median daily THg intake was 20.3 (95% confidence interval 0.72-232.5) ng/kgbw. MeHg was not detected in 213 samples with dietary THg concentrations below 1 ng/g. The MeHg concentration with THg concentrations of 1 ng/g or higher was 1.70 (0.87-6.21) ng/g, and MeHg percentage in THg was 90.0%. To estimate MeHg intake, we multiplied the THg concentration by 90.0%, resulting in an estimated MeHg intake of 18.3 (0.65-209.2) ng/kgbw/day. The THg in children's hair was 1.05 (0.31-3.96) ppm, and a weak positive correlation was observed between hair THg and dietary MeHg (r = 0.170).
CONCLUSIONS
This study highlights the accurate estimation of MeHg intake in children using a duplicate method. Japanese children consume fish, the MeHg intakes exceeded the reference dose and/or provisional tolerable weekly intake in several children. Further discussion based on epidemiological data is required.
Topics: Humans; Methylmercury Compounds; Infant; Child, Preschool; Hair; Japan; Female; Male; Food Contamination; Dietary Exposure; Diet; Infant, Newborn; Environmental Pollutants; Mercury; Infant Food
PubMed: 38735736
DOI: 10.1265/ehpm.24-00048 -
The Science of the Total Environment Jul 2024Telomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation,...
BACKGROUND
Telomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL.
METHODS
Study participants are 6-11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run.
RESULTS
We found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 μg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found.
DISCUSSION
We found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.
Topics: Humans; Child; DNA, Mitochondrial; Mercury; Female; Male; Europe; Telomere; Environmental Exposure; Methylmercury Compounds; Oxidative Stress
PubMed: 38729362
DOI: 10.1016/j.scitotenv.2024.173014 -
The Science of the Total Environment Jun 2024Methylmercury (MeHg) readily bioaccumulates and biomagnifies in aquatic food webs leading to elevated concentrations in fish and may thus induce toxicity. Oxidative...
Methylmercury (MeHg) readily bioaccumulates and biomagnifies in aquatic food webs leading to elevated concentrations in fish and may thus induce toxicity. Oxidative stress is a suggested effect of MeHg bioaccumulation in fish. However, studies on how MeHg triggers oxidative stress in wild fish are scarce. The purpose of this study was to link the subcellular distribution of MeHg in the liver of northern pike from the St. Maurice River (Québec, Canada), affected by two run-of-river (RoR) dams, artificial wetlands, forest fires, and logging activity, to lipid peroxidation as an indicator of oxidative stress. We also evaluated the protective effects of the glutathione (GSH) system and selenium (Se), as they are known to alleviate MeHg toxicity. A customized subcellular partitioning protocol was used to separate the liver into metal-sensitive (mitochondria, microsome/lysosome and HDP - heat-denatured proteins) and metal-detoxified fractions (metal-rich granules and HSP - heat-stable proteins). We examined the relation among THg, MeHg, and Se concentration in livers and subcellular fractions, and the hepatic ratio of total GSH (GSH) to oxidized glutathione (GSSG) on lipid peroxidation levels, using the concentrations of malondialdehyde (MDA), a product of lipid peroxidation. Results showed that hepatic MDA concentration was positively correlated with the combined MeHg and Se concentrations in northern pike liver (r = 0.88, p < 0.001) and that MDA concentrations were best predicted by MeHg associated with the mitochondria (r = 0.71, p < 0.001). This highlights the need for additional research on the MeHg influence on fish health and the interactions between Hg and Se in northern pike.
Topics: Animals; Methylmercury Compounds; Lipid Peroxidation; Esocidae; Liver; Water Pollutants, Chemical; Oxidative Stress; Mitochondria, Liver; Quebec; Environmental Monitoring
PubMed: 38703851
DOI: 10.1016/j.scitotenv.2024.172703 -
Journal of Hazardous Materials Jul 2024Mercury (Hg) contaminated paddy soils are hot spots for methylmercury (MeHg) which can enter the food chain via rice plants causing high risks for human health. Biochar...
Mercury (Hg) contaminated paddy soils are hot spots for methylmercury (MeHg) which can enter the food chain via rice plants causing high risks for human health. Biochar can immobilize Hg and reduce plant uptake of MeHg. However, the effects of biochar on the microbial community and Hg (de)methylation under dynamic redox conditions in paddy soils are unclear. Therefore, we determined the microbial community in an Hg contaminated paddy soil non-treated and treated with rice hull biochar under controlled redox conditions (< 0 mV to 600 mV) using a biogeochemical microcosm system. Hg methylation exceeded demethylation in the biochar-treated soil. The aromatic hydrocarbon degraders Phenylobacterium and Novosphingobium provided electron donors stimulating Hg methylation. MeHg demethylation exceeded methylation in the non-treated soil and was associated with lower available organic matter. Actinobacteria were involved in MeHg demethylation and interlinked with nitrifying bacteria and nitrogen-fixing genus Hyphomicrobium. Microbial assemblages seem more important than single species in Hg transformation. For future directions, the demethylation potential of Hyphomicrobium assemblages and other nitrogen-fixing bacteria should be elucidated. Additionally, different organic matter inputs on paddy soils under constant and dynamic redox conditions could unravel the relationship between Hg (de)methylation, microbial carbon utilization and nitrogen cycling.
Topics: Oxidation-Reduction; Oryza; Soil Microbiology; Soil Pollutants; Charcoal; Methylation; Methylmercury Compounds; Mercury; Bacteria
PubMed: 38696958
DOI: 10.1016/j.jhazmat.2024.134446 -
The Journal of Toxicological Sciences 2024Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages... (Comparative Study)
Comparative Study
Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.
Topics: Animals; Ganglia, Spinal; Methylmercury Compounds; Schwann Cells; Cell Survival; Cells, Cultured; Large Neutral Amino Acid-Transporter 1; Multidrug Resistance-Associated Proteins; Peripheral Nerves; Male; Rats; Multidrug Resistance-Associated Protein 2; ATP-Binding Cassette Transporters
PubMed: 38692911
DOI: 10.2131/jts.49.241 -
Ecotoxicology and Environmental Safety Jun 2024Methylmercury (MeHg) is a neurotoxin associated with foetal neurodevelopmental and adult cognitive deficits. Neurons are highly dependent on the tricarboxylic acid cycle...
Methylmercury (MeHg) is a neurotoxin associated with foetal neurodevelopmental and adult cognitive deficits. Neurons are highly dependent on the tricarboxylic acid cycle and oxidative phosphorylation to produce ATP and meet their high energy demands. Therefore, mitochondrial quality control (MQC) is critical for neuronal homeostasis. While existing studies have generated a wealth of data on the toxicity of MeHg, the complex cascades and molecular pathways governing the mitochondrial network remain to be elucidated. Here, 0.6, 1.2 and 2.4 mg/kg body weight of MeHg were administered intragastrically to pregnant Sprague Dawley rats to model maternal MeHg exposure. The results of the in vivo study revealed that MeHg-treated rats tended to perform more directionless repetitive strategies in the Morris Water Maze and fewer target-orientation strategies than control offspring. Moreover, pathological injury and synaptic toxicity were observed in the hippocampus. Transmission electron microscopy (TEM) demonstrated that the autophagosomes encapsulated damaged mitochondria, while showing a typical mitochondrial fission phenotype, which was supported by the activation of PINK1-dependent key regulators of mitophagy. Moreover, there was upregulation of DRP1 and FIS1. Additionally, MeHg compensation promoted mitochondrial biogenesis, as evidenced by the activation of the mitochondrial PGC1-α-NRF1-TFAM signalling pathway. Notably, SIRT3/AMPK was activated by MeHg, and the expression and activity of p-AMPK, p-LKB1 and SIRT3 were consistently coordinated. Collectively, these findings provide new insights into the potential molecular mechanisms regulating MeHg-induced cognitive deficits through SIRT3/AMPK MQC network coordination.
Topics: Methylmercury Compounds; Animals; Mitochondria; Rats, Sprague-Dawley; Rats; Female; Cognitive Dysfunction; Pregnancy; Hippocampus; Maternal Exposure; Prenatal Exposure Delayed Effects
PubMed: 38678690
DOI: 10.1016/j.ecoenv.2024.116360 -
International Journal of Molecular... Mar 2024Methylmercury is a known environmental pollutant that exhibits severe neurotoxic effects. However, the mechanism by which methylmercury causes neurotoxicity remains...
Methylmercury is a known environmental pollutant that exhibits severe neurotoxic effects. However, the mechanism by which methylmercury causes neurotoxicity remains unclear. To date, we have found that oxidative stress-induced growth inhibitor 1 (OSGIN1), which is induced by oxidative stress and DNA damage, is also induced by methylmercury. Therefore, in this study, we investigated the relationship between methylmercury toxicity and the induction of OSGIN1 expression using C17.2 cells, which are mouse brain neural stem cells. Methylmercury increased both OSGIN1 mRNA and protein levels in a time- and concentration-dependent manner. Moreover, these increases were almost entirely canceled out by pretreatment with actinomycin D, a transcription inhibitor. Furthermore, similar results were obtained from cells in which expression of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) was suppressed, indicating that methylmercury induces OSGIN1 expression via NRF2. Methylmercury causes neuronal cell death by inducing apoptosis. Therefore, we next investigated the role of OSGIN1 in methylmercury-induced neuronal cell death using the activation of caspase-3, which is involved in apoptosis induction, as an indicator. As a result, the increase in cleaved caspase-3 (activated form) induced by methylmercury exposure was decreased by suppressing OSGIN1, and the overexpression of OSGIN1 further promoted the increase in cleaved caspase-3 caused by methylmercury. These results suggest, for the first time, that OSGIN1 is a novel factor involved in methylmercury toxicity, and methylmercury induces apoptosis in C17.2 cells through the induction of OSGIN1 expression by NRF2.
Topics: Animals; Mice; Caspase 3; Methylmercury Compounds; NF-E2-Related Factor 2; Apoptosis; Neurotoxicity Syndromes; Neural Stem Cells
PubMed: 38612696
DOI: 10.3390/ijms25073886 -
Environment International Apr 2024Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood-brain barrier and cause irreversible damage to the human...
Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood-brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress.
Topics: Methylmercury Compounds; NLR Family, Pyrin Domain-Containing 3 Protein; Microglia; Autophagy; Mice; Inflammasomes; Animals; Inflammation; Reactive Oxygen Species; Cell Line; Cell Survival
PubMed: 38588609
DOI: 10.1016/j.envint.2024.108631 -
BioRxiv : the Preprint Server For... Mar 2024Despite the potential toxicity of commercial chemicals to the development of the nervous system (known as developmental neurotoxicity or DNT), conventional cell models...
Despite the potential toxicity of commercial chemicals to the development of the nervous system (known as developmental neurotoxicity or DNT), conventional cell models have primarily been employed for the assessment of acute neuronal toxicity. On the other hand, animal models used for the assessment of DNT are not physiologically relevant due to the heterogenic difference between humans and animals. In addition, animal models are low-throughput, time-consuming, expensive, and ethically questionable. Recently, human brain organoids have emerged as a promising alternative to assess the detrimental effects of chemicals on the developing brain. However, conventional organoid culture systems have several technical limitations including low throughput, lack of reproducibility, insufficient maturity of organoids, and the formation of the necrotic core due to limited diffusion of nutrients and oxygen. To address these issues and establish predictive DNT models, cerebral organoids were differentiated in a dynamic condition in a unique pillar/perfusion plate, which were exposed to test compounds to evaluate DNT potential. The pillar/perfusion plate facilitated uniform, dynamic culture of cerebral organoids with improved proliferation and maturity by rapid, bidirectional flow generated on a digital rocker. Day 9 cerebral organoids in the pillar/perfusion plate were exposed to ascorbic acid (DNT negative) and methylmercury (DNT positive) in a dynamic condition for 1 and 3 weeks, and changes in organoid morphology and neural gene expression were measured to determine DNT potential. As expected, ascorbic acid didn't induce any changes in organoid morphology and neural gene expression. However, exposure of day 9 cerebral organoids to methylmercury resulted in significant changes in organoid morphology and neural gene expression. Interestingly, methylmercury did not induce adverse changes in cerebral organoids in a static condition, thus highlighting the importance of dynamic organoid culture in DNT assessment.
PubMed: 38559002
DOI: 10.1101/2024.03.11.584506 -
Toxics Mar 2024Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial...
Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 μg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, = 0.010) and 95.9% (95%CI 16-230.8%, = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.
PubMed: 38535945
DOI: 10.3390/toxics12030212