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Scientific Reports Jan 2024Tree canopies are known to elevate atmospheric inputs of both mercury (Hg) and methylmercury (MeHg). While foliar uptake of gaseous Hg is well documented, little is...
Tree canopies are known to elevate atmospheric inputs of both mercury (Hg) and methylmercury (MeHg). While foliar uptake of gaseous Hg is well documented, little is known regarding the temporal dynamics and origins of MeHg in tree foliage, which represents typically less than 1% of total Hg in foliage. In this work, we examined the foliar total Hg and MeHg content by following the growth of five individual trees of American Beech (Fagus grandifolia) for one growing season (April-November, 2017) in North Carolina, USA. We show that similar to other studies foliar Hg content increased almost linearly over time, with daily accumulation rates ranging from 0.123 to 0.161 ng/g/day. However, not all trees showed linear increases of foliar MeHg content along the growing season; we found that 2 out of 5 trees showed elevated foliar MeHg content at the initial phase of the growing season but their MeHg content declined through early summer. However, foliar MeHg content among all 5 trees showed eventual increases through the end of the growing season, proving that foliage is a net accumulator of MeHg while foliar gain of biomass did not "dilute" MeHg content.
Topics: Methylmercury Compounds; Trees; Environmental Monitoring; Mercury; Biomass; Water Pollutants, Chemical
PubMed: 38242950
DOI: 10.1038/s41598-024-51469-x -
Journal of Hazardous Materials Mar 2024Mercury is a hazardous pollutant of global concern. While advances have been made in identifying the detrimental effects caused by Hg species in phytoplankton, knowledge...
Mercury is a hazardous pollutant of global concern. While advances have been made in identifying the detrimental effects caused by Hg species in phytoplankton, knowledge gaps remain regarding the metabolomic perturbations induced by inorganic mercury (Hg(II)) and monomethylmercury (MeHg) in these organisms. Diatoms represent a major phytoplankton group essential in various global biogeochemical cycles. The current study combined targeted metabolomics, bioaccumulation, and physiological response assays to investigate metabolic perturbations in diatom Cyclotella meneghiniana exposed for 2 h to nanomolar concentrations of Hg(II) and MeHg. Our findings highlight that such exposures induce reprogramming of the metabolism of amino acids, nucleotides, fatty acids, carboxylic acids and antioxidants. These alterations were primarily mercury-species dependent. MeHg exposure induced more pronounced reprogramming of the metabolism of diatoms than Hg(II), which led to less pronounced effects on ROS generation, membrane permeability and chlorophyll concentrations. Hg(II) treatments presented distinct physiological responses, with more robust metabolic perturbations at higher exposures. The present study provides first-time insights into the main metabolic alterations in diatom C. meneghiniana during short-term exposure to Hg species, deepening our understanding of the molecular basis of these perturbations.
Topics: Mercury; Diatoms; Methylmercury Compounds; Metabolic Reprogramming; Phytoplankton; Fresh Water; Water Pollutants, Chemical
PubMed: 38150761
DOI: 10.1016/j.jhazmat.2023.133245 -
SLAS Discovery : Advancing Life... Apr 2024Three-dimensional (3D) cell culture in vitro promises to improve representation of neuron physiology in vivo. This inspired development of a 3D culture platform for...
Three-dimensional (3D) cell culture in vitro promises to improve representation of neuron physiology in vivo. This inspired development of a 3D culture platform for LUHMES (Lund Human Mesencephalic) dopaminergic neurons for high-throughput screening (HTS) of chemicals for neurotoxicity. Three culture platforms, adhesion (2D-monolayer), 3D-suspension, and 3D-shaken, were compared to monitor mRNA expression of seven neuronal marker genes, DCX, DRD2, ENO2, NEUROD4, SYN1, TH, and TUBB3. These seven marker genes reached similar maxima in all three formats, with the two 3D platforms showing similar kinetics, whereas several markers peaked earlier in 2D adhesion compared to both 3D culture platforms. The differentiated LUHMES (dLUHMES) neurons treated with ziram, methylmercury or thiram dynamically increased expression of metallothionein biomarker genes MT1G, MT1E and MT2A at 6 h. These gene expression increases were generally more dynamic in 2D adhesion cultures than in 3D cultures, but were generally comparable between 3D-suspension and 3D-u plate (low binding) platforms. Finally, we adapted 3D-suspension culture of dLUHMES and neural stem cells to 1536 well plates with a HTS cytotoxicity assay. This HTS assay revealed that cytotoxicity IC values were not significantly different between adhesion and 3D-suspension platforms for 31 of 34 (91%) neurotoxicants tested, whereas IC values were significantly different for at least two toxicants. In summary, the 3D-suspension culture platform for LUHMES dopaminergic neurons supported full differentiation and reproducible assay results, enabling quantitative HTS (qHTS) for cytotoxicity in 1536 well format with a Robust Z' score of 0.68.
Topics: High-Throughput Screening Assays; Dopaminergic Neurons; Humans; Cell Culture Techniques; Cell Differentiation; Cell Culture Techniques, Three Dimensional; Biomarkers; Methylmercury Compounds; Neurotoxins; Cell Line; Cells, Cultured
PubMed: 38280460
DOI: 10.1016/j.slasd.2024.01.004 -
Archives of Toxicology Oct 2023Fetal development is one of the most sensitive windows to methylmercury (MeHg) toxicity. Laboratory and epidemiological studies have shown a dose-response relationship...
Fetal development is one of the most sensitive windows to methylmercury (MeHg) toxicity. Laboratory and epidemiological studies have shown a dose-response relationship between fetal MeHg exposure and neuro performance in different life stages from infants to adults. In addition, MeHg exposure has been reported to be associated with disorders in endoderm-derived organs, such as morphological changes in liver cells and pancreatic cell dysfunctions. However, the mechanisms of the effects of MeHg on non-neuronal organs or systems, especially during the early development of endoderm-derived organs, remain unclear. Here we determined the effects of low concentrations of MeHg exposure during the differentiation of definitive endoderm (DE) cells from human embryonic stem cells (hESCs). hESCs were exposed to MeHg (0, 10, 100, and 200 nM) that covers the range of Hg concentrations typically found in human maternal blood during DE cell induction. Transcriptomic analysis showed that sub-lethal doses of MeHg exposure could alter global gene expression patterns during hESC to DE cell differentiation, leading to increased expression of endodermal genes/proteins and the over-promotion of endodermal fate, mainly through disrupting calcium homeostasis and generating ROS. Bioinformatic analysis results suggested that MeHg exerts its developmental toxicity mainly by disrupting ribosome biogenesis during early cell lineage differentiation. This disruption could lead to aberrant growth or dysfunctions of the developing endoderm-derived organs, and it may be the underlying mechanism for the observed congenital diseases later in life. Based on the results, we proposed an adverse outcome pathway for the effects of MeHg exposure during human embryonic stem cells to definitive endoderm differentiation.
Topics: Adult; Infant; Humans; Methylmercury Compounds; Human Embryonic Stem Cells; Endoderm; Adverse Outcome Pathways; Cell Differentiation
PubMed: 37612375
DOI: 10.1007/s00204-023-03580-7 -
Molecules (Basel, Switzerland) Sep 2023The anthropogenic release of Hg is associated with an increased human exposure risk. Since Hg and MeHg have a high affinity for thiols, their interaction with...
The anthropogenic release of Hg is associated with an increased human exposure risk. Since Hg and MeHg have a high affinity for thiols, their interaction with L-glutathione (GSH) within mammalian cells is fundamentally involved in their toxicological chemistry and excretion. To gain insight into the interaction of these mercurials with multiple small molecular weight thiols, we have investigated their competitive interactions with GSH and N-acetylcysteine (NAC) at near-physiological conditions, using a liquid chromatographic approach. This approach involved the injection of each mercurial onto a reversed-phase (RP)-HPLC column (37 °C) using a PBS buffer mobile phase containing 5.0 mM GSH to simulate cytosolic conditions with Hg being detected in the column effluent by an inductively coupled plasma atomic emission spectrometer (ICP-AES). When the 5.0 mM GSH mobile phase was amended with up to 10 mM NAC, gradually increasing retention times of both mercurials were observed. To explain this behavior, the experiment with 5.0 mM NAC and 5.0 mM GSH was replicated using 50 mM Tris buffer (pH 7.4), and the Hg-containing fractions were analyzed by electrospray ionization mass spectrometry. The results revealed the presence of Hg(GS)(NAC) and Hg(NAC) for Hg and MeHg(GS) and MeHg(NAC) for MeHg, which suggests that the coordination/displacement of GS-moieties from each mercurial by the more hydrophobic NAC can explain their retention behavior. Since the biotransformations of both mercurials were observed at near-physiological conditions, they are of toxicological relevance as they provide a biomolecular explanation for some results that were obtained when animals were administered with each mercurial and NAC.
Topics: Animals; Humans; Acetylcysteine; Methylmercury Compounds; Mercury; Glutathione; Sulfhydryl Compounds; Mammals
PubMed: 37836605
DOI: 10.3390/molecules28196762 -
Environmental Health and Preventive... 2024Methylmercury (MeHg), the causative agent of Minamata disease, damages the cranial nervous system and causes specific sensory disturbances, especially hypoesthesia, in...
BACKGROUND
Methylmercury (MeHg), the causative agent of Minamata disease, damages the cranial nervous system and causes specific sensory disturbances, especially hypoesthesia, in the extremities. However, recent reports demonstrate that patients with chronic Minamata disease conversely develop neuropathic pain in the lower extremities. Studies on our established Minamata disease model rats showed that MeHg-mediated neurodegeneration might induce neuropathic pain by over time through inducing rewiring with neuronal activation in the somatosensory cortex via microglial activation in the spinal dorsal horn.
METHODS
In this study, the effects of gabapentin, a potentially effective treatment for neuropathic pain, was evaluated using this Minamata disease model rats. To further elucidate the mechanism of its medicinal effects, histochemical and biochemical analyses of the nervous system of Minamata disease model rats were conducted.
RESULTS
Gabapentin treatment restored the reduction in the pain threshold caused by MeHg exposure in rats. Histochemical and biochemical analyses revealed that gabapentin showed no effect on MeHg-induced neurodegeneration in entire nervous system and microglial activation in the spinal dorsal horn. However, it was shown that gabapentin may reduce excessive synaptogenesis through its antagonist action on the alpha2-delta-1 subunit of calcium channels in the somatosensory cortex.
CONCLUSIONS
These results indicate that gabapentin may alleviated neuropathic pain in MeHg poisoning, as typified by Minamata disease, by reversibly modulation synaptic rewiring in the somatosensory cortex.
Topics: Animals; Gabapentin; Neuralgia; Rats; Male; Disease Models, Animal; Methylmercury Compounds; Analgesics; Amines; Cyclohexanecarboxylic Acids; gamma-Aminobutyric Acid; Rats, Wistar
PubMed: 38825526
DOI: 10.1265/ehpm.24-00035 -
Environmental Science & Technology Dec 2023Run-of-river (ROR) power plants impound limited terrestrial areas compared to traditional hydropower plants with large reservoirs and are assumed to have reduced impacts...
Run-of-river (ROR) power plants impound limited terrestrial areas compared to traditional hydropower plants with large reservoirs and are assumed to have reduced impacts on mercury cycling. We conducted a study on periphyton and benthic communities from different habitats of the St. Maurice River (Québec, Canada) affected by two ROR power plants and their effect on the bioaccumulation and biomagnification of monomethylmercury (MMHg). Proportion of total mercury as MMHg reached maximum values about 2.9 times higher in flooded sites compared to unflooded sites. Impoundment by ROR would therefore provide favorable environments for the growth of periphyton, which can produce and accumulate MMHg. Periphyton MMHg concentrations significantly explained concentrations in some benthic macroinvertebrates, reflecting a local transfer. Through the analysis of δC and δN signatures, we found that flooding, creating scattered lenthic habitats, led to modifications in trophic structures by the introduction of new organic matter sources. The computed trophic magnification slopes did not show significant differences in the transfer efficiency of MMHg between sectors, while intercepts of flooded sectors were higher. Increases in MMHg concentrations in flooded areas are likely due to the impoundment, combined with watershed disturbances, and the creation of small habitats favorable to periphyton should be included in future predictive models.
Topics: Animals; Food Chain; Bioaccumulation; Rivers; Mercury; Biofilms; Water Pollutants, Chemical; Environmental Monitoring; Fishes; Methylmercury Compounds
PubMed: 38016692
DOI: 10.1021/acs.est.3c05585 -
Ecotoxicology and Environmental Safety Jan 2024The Petit Saut hydroelectric dam and the upstream and downstream areas of the Sinnamary River in French Guiana (Amazon basin) have been studied from 1993 to 2020. The...
The Petit Saut hydroelectric dam and the upstream and downstream areas of the Sinnamary River in French Guiana (Amazon basin) have been studied from 1993 to 2020. The nearly thirty-years-long study of the monitoring of total mercury concentration in fish and the physicochemical survey of the environment made it possible to demonstrate the impact of the flooding of the forest and the role of the hydroelectric dam on the methylation of mercury. Results show that the physicochemical modifications generated by the construction of the dam led to a significant production of methylmercury (MeHg) in the anoxic part of the reservoir and downstream of the river leading to a strong spatio-temporal impact of the dam. Seven species of fishes are studied and their mercury concentrations vary according to many parameters: fish diet, position in the water column, site, lake oxycline level and time.
Topics: Animals; Mercury; French Guiana; Environmental Monitoring; Water Pollutants, Chemical; Methylmercury Compounds; Fishes
PubMed: 38100848
DOI: 10.1016/j.ecoenv.2023.115771 -
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 -
Food and Chemical Toxicology : An... Jul 2023Humans are mainly exposed to mercury (Hg) through contaminated foodstuffs. However, the effects of Hg on the intestinal tract have received little attention. We...
Humans are mainly exposed to mercury (Hg) through contaminated foodstuffs. However, the effects of Hg on the intestinal tract have received little attention. We performed a subchronic exposure to inorganic mercury or methylmercury in mice through drinking water (1, 5 or 10 mg/L for four months) to evaluate their intestinal impact. Histological, biochemical and gene expression analyses showed that both Hg species induced oxidative stress in small intestine and colon, while inflammation was mainly detected in the colon. Increased fecal albumin content indicated a compromised epithelial barrier. Mucus production was possibly also affected, as an increase in Muc2 expression was detected. However, differential effects were detected between both Hg species. Activation of p38 MAPK and increased crypt depth were detected in colon only with MeHg. Minor differences in microbiota composition were detected between unexposed and exposed mice. Although significant differences were detected between both Hg species at 10 mg/L, only the relative abundances of low abundance taxa were affected. Concentrations of microbial-derived short-chain fatty acids were decreased, suggesting an effect on microbial metabolism or increased demand by the intestinal epithelium. Results obtained confirm previous in vitro studies and highlights the intestinal mucosa as an initial target of Hg.
Topics: Humans; Animals; Mice; Methylmercury Compounds; Mercury; Reactive Oxygen Species; Microbiota; Intestinal Mucosa
PubMed: 37137463
DOI: 10.1016/j.fct.2023.113801