Methylmercury Toxicity Research Articles

Health Impacts and Biomarkers of Prenatal Exposure to Methylmercury: Lessons from Minamata, Japan.

The main chemical forms of mercury are elemental mercury, inorganic divalent mercury, and methylmercury, which are metabolized in different ways and have differing toxic effects in humans. Among the various chemical forms of mercury, methylmercury is known to be particularly neurotoxic, and was identified as the cause of Minamata disease. It bioaccumulates in fish and shellfish via aquatic food webs, and fish and sea mammals at high trophic levels exhibit high mercury concentrations. Most human methylmercury exposure occurs through seafood consumption. Methylmercury easily penetrates the blood-brain barrier and so can affect the nervous system. Fetuses are known to be at particularly high risk of methylmercury exposure. In this review, we summarize the health effects and exposure assessment of methylmercury as follows: (1) methylmercury toxicity, (2) history and background of Minamata disease, (3) methylmercury pollution in the Minamata area according to analyses of preserved umbilical cords, (4) changes in the sex ratio in Minamata area, (5) neuropathology in fetuses, (6) kinetics of methylmercury in fetuses, (7) exposure assessment in fetuses.

Brain methylmercury uptake in fetal, neonate, weanling, and adult rats

Fetuses and neonates are known to be highly susceptible to methylmercury (MeHg) toxicity, but little is known about the relative uptake of MeHg from blood to the developing brain. We measured time-course changes in mercury (Hg) concentrations in the brain of fetal, neonate, weanling, and adult rats after an injection of 0.08 μg (0.4 nmol) Hg/g MeHg. In the prenatal experiment, MeHg was subcutaneously injected to pregnant dams on embryonic days 17, 18, 18.5, 19, 19.5, or 20, and Hg concentrations in tissues were measured in both mothers and fetuses on embryonic day 21 (1 day before parturition). Brain Hg levels in fetuses peaked 2 days after injection and were approximately 1.5 times higher than in mothers. In the postnatal experiment, the same MeHg dose was injected subcutaneously to male rats on postnatal days 1 (neonates), 35 (weanlings), or 56 (adults). Mercury concentrations in tissues were measured 1, 2, 3, 4, 5, or 6 days after the injection. Brain Hg levels peaked most rapidly in neonates, and were approximately 1.5 times higher than levels in weanlings or adults. Throughout the examined period, peak Hg levels in the brain and the Hg brain/blood ratio 24 h after injection were highest in fetuses, followed by the levels in neonates, and decreased with life stage. These findings suggest that relatively higher brain MeHg uptake is an important factor in the vulnerability of fetuses and neonates to MeHg exposure.

Chemokine CCL4 Induced in Mouse Brain Has a Protective Role against Methylmercury Toxicity.

Methylmercury (MeHg) is selectively toxic to the central nervous system, but mechanisms related to its toxicity are poorly understood. In the present study, we identified the chemokine, C-C motif Chemokine Ligand 4 (CCL4), to be selectively upregulated in the brain of MeHg-administered mice. We then investigated the relationship between CCL4 expression and MeHg toxicity using in vivo and in vitro approaches. We confirmed that in C17.2 cells (a mouse neural stem cell line) and the mouse brain, induction of CCL4 expression occurs prior to cytotoxicity caused by MeHg. We also show that the addition of recombinant CCL4 to the culture medium of mouse primary neurons attenuated MeHg toxicity, while knockdown of CCL4 in C17.2 cells resulted in higher MeHg sensitivity compared with control cells. These results suggest that CCL4 is a protective factor against MeHg toxicity and that induction of CCL4 expression is not a result of cytotoxicity by MeHg but is a protective response against MeHg exposure.

Mercury Toxicity: Ecological Features of Organic Phase of Mercury in Biota- Part I

Mercury is extensively used in industry with top usage in electrolytic chlorine. As a result of this elemental consumption in industry, different forms of inorganic and organic mercury get into the environment in great piles every day and many of these mercurial derivatives are converted to methylmercury by microorganisms. The study is assigned to inspect the ecological features of organic mercury species in biological and marine environments. In addition, the paper takes into account the uptake and the distribution of mercury in fish to investigate the conversion and mobilization of mercury from sediment deposits into the general environment. It has been confirmed that the biological half-life of methylmercury in human is about 70 days. In methodology, molecular identification of mercury has been defined. Monomethyl mercury in sediments was analyzed by gas chromatography (GC) hyphenated with electron capture detector (ECD) and the confirmation was measured by mass spectroscopy (MS). The conversion of mercury element to its organic species has been illustrated. In soil, it was found that lower pH favors monomethyl mercury and the higher pH, dimethylmercury formation, respectively. Dimethylmercury is the biological poisoning product and methylmercury is an artifact of isolation procedure. In next paper, we will turn to study the epidemiological features of organic phase of mercury and investigate in deep the distribution, metabolism, and toxicity of mercury and methylmercury in some essential raw food materials, domestic animal feedstock, and some other biological specimens using basically simple analytical methods of chromatography as paper (PC) and thin layer (TLC).

Awareness of Listeriosis and Methylmercury toxicity public health recommendations and diet during pregnancy

BackgroundAwareness of Listeriosis and Methylmercury toxicity recommendations are associated with decreased intake of high-risk foods. Whether awareness of the recommendations affect dietary quality of pregnant women in Australian is unknown. AimTo evaluate awareness of Listeriosis and Methylmercury toxicity recommendations during pregnancy and its impact on dietary quality. MethodsPregnant women (n=81) were recruited from antenatal clinics. Awareness of Listeriosis and Methylmercury toxicity recommendations and high-risk foods consumption were assessed via questionnaire at 10–23 weeks gestation. Diet quality was measured using the 2005 Healthy Eating Index using a validated food frequency questionnaire at 10–23 and 34–36 weeks gestation. FindingsA higher proportion of women were aware of Methylmercury toxicity compared with Listeriosis recommendations (75.3 vs. 59.2%, p<0.001). The proportion of women who decreased or avoided consumption of certain high-risk Listeriosis foods were higher in those who were aware compared with those who were unaware of Listeriosis recommendations [raw fish (96.0 vs 69.2%, p=0.046), soft-serve ice cream (93.9 vs 58.3%, p=0.004) and alfalfa/bean sprouts (68.7 vs 28.5%, p=0.006)]. A large proportion of women (96.8%) met recommendations for limiting consumption of high Methylmercury fish. There was no difference in the change in dietary quality over pregnancy regardless of women’s awareness of the recommendations. Discussion and conclusionsAwareness of Listeriosis and Methylmercury toxicity recommendations has little impact on dietary quality of pregnant women in this small study. Further research in a large representative population of pregnant women is needed to confirm our findings and to optimise dietary quality during pregnancy.

Mercury Methylation Capacity and Removal of Hg Species from Aqueous Medium by Cyanobacteria

Most technologies used for decontamination presents good results for high concentrations, but limitations for lower ones. The desirable Hg concentration in the water is extremely low because of its toxicity. The aims of this study were to evaluate inorganic mercury (Hg2+) and methylmercury (CH3Hg+) toxicity in Nostoc paludosum, to assess the potential of this cyanobacteria strain to remove these Hg species from aqueous medium and also to investigate Hg methylation by the cyanobacteria. CH3Hg+ determination was performed by gas chromatography-pyrolysis-atomic fluorescence spectrometry in cultures exposed to a concentration of 20 μg L−1 for 30 days. Both Hg species were removed from the supernatant, ranging from 73 to 96% of Hg2+ and from 73 to 95% of CH3Hg+. Ultrastructural Hg2+ effects in the cyanobacteria cells investigated by transmission electron microscopy revealed higher production of glycogen, cyanophycin, and intrathylacoidal spaces than the control group. When Hg was added to the culture in the form of CH3Hg+, a decrease corresponding to approximately 60% of the initial concentration due to Hg volatilization was observed. The production of CH3Hg+ by the cyanobacteria was detected in concentrations near the limit of detection (0.0025%) of the bioaccumulated THg. This is an advantage for biotechnological decontamination applications, as CH3Hg+ is a very toxic specie and can be bioaccumulated and biomagnified. The results demonstrated that cyanobacteria cells are an efficient alternative to retain and/or remove Hg at low concentrations and they constitute a potential tool for a “final cleaning” of contaminated waste water.

Methylmercury alters proliferation, migration, and antioxidant capacity in human HTR8/SV-neo trophoblast cells

Methylmercury, a potent neurotoxin, is able to pass through the placenta, but its effects on the placenta itself have not been elucidated. Using an immortalized human trophoblast cell line, HTR8/SV-neo, we assessed the in vitro toxicity of methylmercury. We found that 1 μg/mL methylmercury decreased viability, proliferation, and migration; and it had effects on antioxidant genes similar to those seen in neural cells. However, methylmercury led to decreased expression of superoxide dismutase 1 and increased expression of surfactant protein D. HTR cells treated 0.01 or 0.1 μg/mL methylmercury had increased migration rates along with decreased expression of an adhesion gene, cadherin 3, suggesting that low doses of methylmercury promote migration in HTR cells. Our results indicate that trophoblast cells react differently to methylmercury relative to neural cell lines, and thus investigation of methylmercury toxicity in placental cells is needed to understand the effects of this heavy metal on the placenta.

Co-exposure of silica nanoparticles and methylmercury induced cardiac toxicity in vitro and in vivo

The released nanoparticles into environment can potentially interact with pre-existing pollution, maybe causing higher toxicity. As such, assessment of their joint toxic effects is necessary. This study was to investigate the co-exposure cardiac toxicity of silica nanoparticles (SiNPs) and methylmercury (MeHg). Factorial design was used to determine the potential joint action type. In vitro study, human cardiomyocytes (AC16) were exposed to SiNPs and MeHg alone or the combination. Higher toxicity was observed on cell viability, cell membrane damage in co-exposure compared with single exposure and control. The co-exposure enhanced the ROS, MDA generation and reduced the activity of SOD and GSH-Px. In addition, the co-exposure induced much higher cellular apoptotic rate in AC16. In vivo study, after SD rats exposed to SiNPs and MeHg and their mixture by intratracheal instillation for 30days, pathological changes (myocardial interstitial edema) of heart were occurred in co-exposure compared with single exposure and control. Moreover obvious ultra-structural changes, including myofibril disorder, myocardial gap expansion, and mitochondrial damage were observed in co-exposure group. The activity of myocardial enzymes, including CK-MB, ANP, BNP and cTnT, were significantly elevated in co-exposure group of rat serum. Meanwhile, the cardiac injury-linked proteins expression showed an increase in SERCA2 and decreased levels of cTnT, ANP and BNP in co-exposure group. Factorial design analysis demonstrated that additive and synergistic interactions were responsible for the co-exposure cardiac toxicity in vitro and vivo. In summary, our results showed severe cardiac toxicity induced by co-exposure of SiNPs and MeHg in both cardiomycytes and heart. It will help to clarify the potential cardiovascular toxicity in regards to combined exposure pollutions.

Putrescine selectively alleviates methylmercury toxicity in C17.2 mouse neural stem cells

Putrescine selectively alleviates methylmercury toxicity in C17.2 mouse neural stem cells

Editor's Highlight: Variation in Methylmercury Metabolism and Elimination Status in Humans Following Fish Consumption.

Evaluating the potential for methylmercury (MeHg) toxicity relies on accurately predicting the mercury (Hg) body burden that results from eating fish. Hg body burden is directly determined by the slow elimination kinetics of MeHg in the human body (kel = 0.014 days-1 or t1/2 =50 days). Existing studies on MeHg half-life in humans demonstrate a wide range values (t1/2 = 30 to >150 days) and has lead to uncertainty in the derivation of a regulatory standard for acceptable daily oral intake. The causes of variation in MeHg toxicokinetics in humans remain little explored. Here we characterize variation in human MeHg metabolism and elimination rate (kel) in 37 adult volunteers who consumed 3 fish meals. We determined MeHg elimination rates via longitudinal Hg analysis in single hairs using laser ablation inductively coupled plasma mass spectrometry. We also measured MeHg metabolism (biotransformation) via speciation of fecal Hg. We find an average kel = 0.0157 days-1 (t1/2 = 44 days) amongst a more than 2-fold variation in kel across the cohort (0.0248-0.0112 days-1; t1/2 = 28-62 days). Although MeHg biotransformation varied widely between individuals, it showed a positive association with elimination rates across the cohort. A more than 2-fold change in kel over a period of 2 years was seen in some individuals. In 2 individuals, who received antibiotic for unrelated health issues, elimination rate was seen to slow significantly. Associations of kel with age, body mass index, gender, and fish eating habits were not observed. We establish that a measure of methylmercury metabolism and eliminaiton status (MerMES) can reduce uncertainty in determining an individual's MeHg toxicokinetics subsequent to eating fish.

Comparison of neurons derived from mouse P19, rat PC12 and human SH-SY5Y cells in the assessment of chemical- and toxin-induced neurotoxicity

BackgroundExposure to chemicals might be toxic to the developing brain. There is a need for simple and robust in vitro cellular models for evaluation of chemical-induced neurotoxicity as a complement to traditional studies on animals. In this study, neuronally differentiated mouse embryonal carcinoma P19 cells (P19 neurons) were compared with human neuroblastoma SH-SY5Y cells and rat adrenal pheochromocytoma PC12 cells for their ability to detect toxicity of methylmercury (MeHg), okadaic acid and acrylamide.MethodsRetinoic acid-treated P19 and SH-SY5Y cells and nerve growth factor-stimulated PC12 cells, allowed to differentiate for 6 days, were exposed to MeHg, okadaic acid and acrylamide for 48 h. Cell survival and neurite outgrowth were assessed with the calcein-AM assay and fluorescence detection of antibodies against the cytoskeletal neuron-specific protein βIII-tubulin, respectively. The effects of glutathione (GSH) and the potent inhibitor of GSH synthesis buthionine sulfoximine (BSO) on the MeHg induced-toxicity were assessed using the PrestoBlue™ cell viability assay and the TMRE mitochondrial membrane potential assay.ResultsDifferentiated P19 cells developed the most extensive neuronal network among the three cell models and were the most sensitive neuronal model to detect neurotoxic effects of the test compounds. MeHg produced a concentration-dependent toxicity in differentiated P19 cells and SH-SY5Y cells, with statistically significant effects at concentrations from 0.1 μM in the P19 neurons and 1 μM in the SH-SY5Y cells. MeHg induced a decrease in the cellular metabolic activity and mitochondrial membrane potential (ΔΨm) in the differentiated P19 cells and SH-SY5Y cells, that were attenuated by GSH. Okadaic acid and acrylamide also showed statistically significant toxicity in the P19 neurons, but not in the SH-SY5Y cells or the P12 cells.ConclusionsP19 neurons are more sensitive to detect cytotoxicity of MeHg, okadaic acid and acrylamide than retinoic acid-differentiated SH-SY5Y cells and nerve growth factor-treated PC12 cells. P19 neurons are at least as sensitive as differentiated SH-SY5Y cells to detect the loss of mitochondrial membrane potential produced by MeHg and the protective effects of extracellular GSH on MeHg toxicity. P19 neurons may be a useful model to study neurotoxic effects of chemicals.

Akr1 attenuates methylmercury toxicity through the palmitoylation of Meh1 as a subunit of the yeast EGO complex.

We previously reported that palmitoyltransferase activity of Akr1 is required for alleviation of methylmercury toxicity in yeast. In this study, we identified a factor that alleviates methylmercury toxicity among the substrate proteins palmitoylated by Akr1, and investigated the role of this factor in methylmercury toxicity. Gene disruption and site-directed mutagenesis were used to examine the relationship of methylmercury toxicity and vacuole function. Palmitoylation was investigated using the acyl-biotinyl exchange method. Vacuoles were stained with the fluorescent probe FM4-64. We found that Meh1 (alias Ego1), a substrate protein of Akr1, participates in the alleviation of methylmercury toxicity. Moreover, almost no palmitoylation of Meh1 when Akr1 was knocked out, and mutant Meh1, which is not palmitoylated, did not show alleviation of methylmercury toxicity. The palmitoylated Meh1 was involved in the alleviation of methylmercury toxicity as a constituent of EGO complex which suppresses autophagy. Methylmercury caused vacuole deformation, and this was greater in the yeasts knocking out the EGO complex subunits. 3-Methyladenine, an autophagy inhibitor, suppresses vacuole deformation and cytotoxicity caused by methylmercury. The elevated methylmercury sensitivity by Meh1 knockout almost completely disappeared in the presence of 3-methyladenine. Akr1 reduces methylmercury toxicity through palmitoylation of Meh1. Furthermore, the EGO complex including Meh1 reduces methylmercury toxicity by suppressing the induction of vacuole deformation caused by methylmercury. These findings propose that Meh1 palmitoylated by Akr1 may act as a constituent of the EGO complex when contributing to the decreased cytotoxicity by negatively controlling the induction of autophagy by methylmercury.

Editor's Highlight: Glutathione S-Transferase Activity Moderates Methylmercury Toxicity During Development in Drosophila.

Glutathione (GSH) pathways play a central role in methylmercury (MeHg) metabolism and elimination, largely due to formation of a more readily transported MeHg-GSH conjugate. Glutathione S-transferases (GSTs) have therefore been proposed to facilitate MeHg elimination by catalyzing MeHg-GSH conjugation. A role for human GSTP1 in MeHg disposition is suggested by the association of two common polymorphisms in the coding region (Ile105Val and Ala114Val) with Hg levels in either blood or hair. In this study, we investigated a functional role for GSTs in modulating MeHg toxicity during development. Using the Drosophila model to execute targeted manipulations of both endogenous GSTs and introduced human GSTP1 variants we correlate gene and protein expression levels with GST activity and also with MeHg body burden and developmental outcomes. RNAi knockdown of endogenous GSTD1, GSTE1, or GSTS1, individually, increased susceptibility to MeHg during pupal development resulting in a reduced rate of adult eclosion. Exogenous expression of human GSTP1 in developing flies resulted in increased MeHg tolerance relative to control flies as seen with elevated eclosion rates when reared on MeHg containing food. Furthermore, the GSTP1105 and GSTP1114 variants showed a reduced enzyme activity relative to wild-type GSTP1 (GSTP1wt). Finally, we observed a trend whereby Hg body burden was inversely related to the levels of GST activity. However, in some instances GSTP1 expression resulted in increased eclosion rates without reducing Hg body burden suggesting that GSTs interact with MeHg via both toxicokinetic and toxicodynamic mechanisms. These findings indicate that GSTs moderate MeHg toxicity during development in our experimental model.

Alluvial Gold Mining Sites as Exposure Pathways for Methyl Mercury Toxicity in Children: A Systematic Review

Extensive studies have showed that alluvial gold mining is a predisposing factor for mercury toxicity through occupational exposure. In our systematic review of related literature, we aim to determine if children of alluvial gold miners were at risk of exposure to methyl mercury toxicity through dietary exposure. This was achieved through applying Cochrane PICO methodology for the research question. We selected only the most relevant articles from the thousands of articles that were generated by the Divine Word University (DWU) electronic data base system for our review. Further screening questions were applied based on the CASP method which filtered remaining 105 to only 9 papers for the review. The results from the nine (N = 9) studies analysed showed convincing results of the association between consumption of fish contaminated with methyl mercury and poor growth and development in children whose parents lived near mining sites. We conclude that since mercury is the predominant element used in the extraction of gold in alluvial mining, it is an exposure pathway for methyl mercury toxicity for children through dietary exposure.

Differences in the responses of three plasma selenium-containing proteins in relation to methylmercury-exposure through consumption of fish/whales

Putative protective effects of selenium (Se) against methylmercury (MeHg) toxicity have been examined but no conclusion has been reached. We recently reported the lack of serious neurological symptoms in a Japanese fish-eating population with high intakes of MeHg and suggested a potential protective role for Se. Here, relationships between levels of Hg and Se in the blood and plasma samples, with a quantitative evaluation of Se-containing proteins, obtained from this population were examined. While levels of the whole-blood Hg (WB-Hg) and plasma Se (P-Se) showed a positive correlation, stratified analysis revealed that they correlated only in samples with higher (greater than the median) levels of MeHg. A food frequency questionnaire showed that consumption of fish/whales correlated with WB-Hg, but not with P-Se, suggesting that the positive correlation between WB-Hg and P-Se might not be the result of co-intake of these elements from seafood. Speciation of plasma Se revealed the differences in the responses of two plasma selenoproteins, glutathione peroxidase (GPx) and selenoprotein P (SePP), in relation to Hg exposure. In the high-Hg group, SePP showed a positive correlation with WB-Hg, but GPx did not. In the low-Hg group, neither SePP nor GPx showed any correlation with WB-Hg. These observations suggest that the increase in P-Se in the high-Hg group might be associated with an increase in SePP, which may, in turn, suggest an increased demand for one or more selenoproteins in various organs, for which SePP supplies the element.

Methylmercury induces the expression of TNF-α selectively in the brain of mice.

Methylmercury selectively damages the central nervous system (CNS). The tumor necrosis factor (TNF) superfamily includes representative cytokines that participate in the inflammatory response as well as cell survival, and apoptosis. In this study, we found that administration of methylmercury selectively induced TNF-α expression in the brain of mice. Although the accumulated mercury concentration in the liver and kidneys was greater than in the brain, TNF-α expression was induced to a greater extent in brain. Thus, it is possible that there may exist a selective mechanism by which methylmercury induces TNF-α expression in the brain. We also found that TNF-α expression was induced by methylmercury in C17.2 cells (mouse neural stem cells) and NF-κB may participate as a transcription factor in that induction. Further, we showed that the addition of TNF-α antagonist (WP9QY) reduced the toxicity of methylmercury to C17.2 cells. In contrast, the addition of recombinant TNF-α to the culture medium decreased the cell viability. We suggest that TNF-α may play a part in the selective damage of the CNS by methylmercury. Furthermore, our results indicate that the higher TNF-α expression induced by methylmercury maybe the cause of cell death, as TNF-α binds to its receptor after being released extracellularly.

Neurotoxicity of Methylmercury in Isolated Astrocytes and Neurons: the Cytoskeleton as a Main Target.

In the present work, we focused on mechanisms of methylmercury (MeHg) toxicity in primary astrocytes and neurons of rats. Cortical astrocytes and neurons exposed to 0.5-5μM MeHg present a link among morphological alterations, glutathione (GSH) depletion, glutamate dyshomeostasis, and cell death. Disrupted neuronal cytoskeleton was assessed by decreased neurite length and neurite/neuron ratio. Astrocytes presented reorganization of actin and glial fibrillary acidic protein (GFAP) networks and reduced cytoplasmic area. Glutamate uptake and Na+K+ATPase activity in MeHg-treated astrocytes were preserved; however, downregulated EAAC1-mediated glutamate uptake was associated with impaired Na+K+ATPase activity in neurons. Oxidative imbalance was found in astrocytes and neurons through increased 2'7'-dichlorofluorescein (DCF) production and misregulated superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GPX) activities. Glutathione (GSH) levels were downregulated in both astrocytes and neurons. MeHg reduced neuronal viability and induced caspase 3-dependent apoptosis together with downregulated PI3K/Akt pathway. In astrocytes, necrotic death was associated with increased TNF-α and JNK/MAPK activities. Cytoskeletal remodeling and cell death were fully prevented in astrocytes and neurons by GSH, but not melatonin or Trolox supplementation. These findings support a role for depleted GSH in the cytotoxicity of MeHg leading to disruption of the cytoskeleton and cell death. Moreover, in neurons, glutamate antagonists also prevented cytoskeletal disruption and neuronal death. We propose that cytoskeleton is an end point in MeHg cytotoxicity. Oxidative imbalance and glutamate mechanisms mediate MeHg cytoskeletal disruption and apoptosis in neurons. Otherwise, redox imbalance and glutamate-independent mechanisms disrupted the cytoskeleton and induced necrosis in MeHg-exposed astrocyte.

An LC–MS-based lipidomics approach for studying the impact of dietary eicosapentaenoic acid on modulating methylmercury toxicity in mice

Methylmercury (MeHg) exposure has been a public health problem for many decades. There is a growing interest in searching for possible dietary nutrients that may affect MeHg toxicity. The study aims to evaluate the impact of eicosapentaenoic acid (EPA) on modulating MeHg toxicity in mice. The study was based on a two-level factorial design, where the factors were presence or absence of EPA and MeHg in the feed. A liquid chromatography-mass spectrometry-based lipidomics approach was used to identify and quantify the main phospholipid species in mouse liver and plasma. The effects of EPA and MeHg on phospholipid species were evaluated by principal component analysis and statistics. Some biochemical and toxicological markers were measured and hepatic histological assay was carried out. EPA treatment significantly elevated the phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) species that contain n-3 PUFA, and reduced the levels of PtdCho and PtdEtn species that contain arachidonic acid (ARA), while MeHg exhibited opposite effects on these specific PtdCho species in liver. MeHg induced higher prostaglandin E2 and lower prostaglandin E3, thus increasing pro-inflammatory factors, while EPA decreased these ARA-derived inflammatory factors. Moreover, MeHg induced chronic inflammatory symptoms in mice, including severe hepatic necrosis, higher aspartate aminotransferase and alanine aminotransferase activities in plasma, higher thiobarbituric acid reactive substances and lower glutathione in liver. These symptoms were all alleviated by EPA treatment. EPA may have protective effect against MeHg-induced toxicity due to the favorable modification of membrane phospholipid composition and inhibition of inflammatory factors.

Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study

BackgroundATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. AimsTo evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Materials and methodsNutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008–2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N=1313) (mean 3.9ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20months of age (N=1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. ResultsSeven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p<0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7ppm) while children with the CT genotype (mean hair Hg 4.0ppm) had intermediate BSID scores. DiscussionGenetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated.

Absence of selenium protection against methylmercury toxicity in harbour seal leucocytes in vitro

Previous studies described high concentrations of mercury (Hg) and selenium (Se) in the blood of harbour seals, Phoca vitulina from the North Sea. In the present study, we evaluated the in vitro potential protective effects of sodium selenite (Na2SeO3) and selenomethionine (SeMet) on cell proliferation of harbour seal lymphocytes exposed to MeHgCl 0.75μM. In vitro exposure of ConA-stimulated T lymphocytes resulted in severe inhibition of DNA synthesis, likely linked to severe loss of mitochondrial membrane potential at 0.75μM. Neither selenite nor SeMet showed a protective effect against MeHg toxicity expressed at the T lymphocyte proliferation level for harbour seals. Selenite and SeMet did not show negative effects regarding lymphocyte proliferation and mitochondrial membrane potential.To conclude, our results clearly demonstrated that MeHg affected in vitro immune cells exposure with no protective effects of selenium at a molar ratio Hg:Se of 1:10 in harbour seals from the North Sea.