Megumi Yamamoto

Stimulation of elemental mercury oxidation in the presence of chloride ion in aquatic environments

The effect of chloride ion (Cl−) on the oxidation of elemental mercury (Hg0) in aqueous solution was studied. Oxidation of Hg0 to mercuric ion was found to be stimulated in the presence of sodium chloride in a dose- and time-dependent manner. The oxidation was also stimulated in the presence of potassium chloride, magnesium chloride or hydrochloric acid, suggesting the participation of Cl− in Hg0 oxidation. Oxidation rate of Hg0 in natural sea water was significantly higher than that in distilled water or natural fresh water. These results indicate that the Hg0 oxidation actually occur in natural aquatic environments, and Cl− would play an important role in the cycling of mercury there.

Selenomethionine Protects against Neuronal Degeneration by Methylmercury in the Developing Rat Cerebrum

Although many experimental studies have shown that selenium protects against methylmercury (MeHg) toxicity at different end points, the direct interactive effects of selenium and MeHg on neurons in the brain remain unknown. Our goal is to confirm the protective effects of selenium against neuronal degeneration induced by MeHg in the developing postnatal rat brain using a postnatal rat model that is suitable for extrapolating the effects of MeHg to the fetal brain of humans. As an exposure source of selenium, we used selenomethionine (SeMet), a food-originated selenium. Wistar rats of postnatal days 14 were orally administered with vehicle (control), MeHg (8 mg Hg/kg/day), SeMet (2 mg Se/kg/day), or MeHg plus SeMet coexposure for 10 consecutive days. Neuronal degeneration and reactive astrocytosis were observed in the cerebral cortex of the MeHg-group but the symptoms were prevented by coexposure to SeMet. These findings serve as a proof that dietary selenium can directly protect neurons against MeHg toxicity in the mammalian brain, especially in the developing cerebrum.

Impaired Lipid and Glucose Homeostasis in Hexabromocyclododecane-Exposed Mice Fed a High-Fat Diet

Background: Hexabromocyclododecane (HBCD) is an additive flame retardant used in the textile industry and in polystyrene foam manufacturing. Because of its lipophilicity and persistency, HBCD accumulates in adipose tissue and thus has the potential of causing metabolic disorders through disruption of lipid and glucose homeostasis. However, the association between HBCD and obesity remains unclear. Objectives: We investigated whether exposure to HBCD contributes to initiation and progression of obesity and related metabolic dysfunction in mice fed a normal diet (ND) or a high-fat diet (HFD). Methods: Male C57BL/6J mice were fed a HFD (62.2 kcal% fat) or a ND and treated orally with HBCD (0, 1.75, 35, or 700 μg/kg body weight) weekly from 6 to 20 weeks of age. We examined body weight, liver weight, blood biochemistry, histopathological changes, and gene expression profiles in the liver and adipose tissue. Results: In HFD-fed mice, body and liver weight were markedly increased in mice treated with the high (700 μg/kg) and medium (35 μg/kg) doses of HBCD compared with vehicle. This effect was more prominent in the high-dose group. These increases were paralleled by increases in random blood glucose and insulin levels and enhancement of microvesicular steatosis and macrophage accumulation in adipose tissue. HBCD-treated HFD-fed mice also had increased mRNA levels of Pparg (peroxisome proliferator-activated receptor-γ) in the liver and decreased mRNA levels of Glut4 (glucose transporter 4) in adipose tissue compared with vehicle-treated HFD-fed mice. Conclusions: Our findings suggest that HBCD may contribute to enhancement of diet-induced body weight gain and metabolic dysfunction through disruption of lipid and glucose homeostasis, resulting in accelerated progression of obesity. Citation: Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. 2014. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health Perspect 122:277–283; http://dx.doi.org/10.1289/ehp.1307421

Bioaccumulation of mercury in a vestimentiferan worm living in Kagoshima Bay, Japan

The present study reports on the mercury concentrations of the vestimentiferan worm, Lamellibrachia satsuma, (Annelida: Pogonophora) found near hydrothermal vents at a depth of 80-100 m in the northern parts of Kagoshima Bay. The vestimentiferan worms had total mercury concentrations of 238 ng/g in the anterior muscle of the body and 164 ng/g in the posterior trophosome. Methylmercury constituted only 7.6% of total mercury detected anteriorly and 16.3% posteriorly. The mean total mercury concentration in filtrated ambient seawater of the worm habitat was 1.1 ng/l. The worm should accumulate mercury in seawater by a one-step into the anterior and posterior parts as 2.2 x 10(%) and 1.5 x 10(5) times those of the filtered ambient seawater, respectively. The bioaccumulation factor of mercury by the worms with only their respiration would be actually larger than that by other marine animals through food webs. The high bioaccumulation factor of mercury in the worms suggest the following two possibilities: (i) the biological half-life of organomercury in the worm could be exceptionally long; or (ii) the lifetime of vestimentiferan worms examined in the present study could be extremely long. Various metals in one specimen of the worm were analyzed by using ICP-MS, and then gold as well as silver were detected in the worm. Gold was detected for the first time from marine animals.

Possible mechanism of elemental mercury oxidation in the presence of SH compounds in aqueous solution

Abstract The oxidation of elemental mercury (Hg 0 ) in the presence of sulfhydryl (SH) compounds in aqueous solution was studied. The order of potency for stimulation of Hg 0 oxidation was glutathione > L-cysteine > D-penicillamine. The consumption rate of each SH residue in the reaction mixture in the presence of Hg 0 showed the same order. Ethylenediaminetetraacetic acid was also found to accelerate Hg 0 oxidation. These results indicated that the oxidation of Hg 0 was stimulated in the presence of compounds with an affinity for the mercuric ion (Hg 2+ ). The accelerated conversion of Hg 0 to ionized Hg 2+ would be the result of a shift in equilibrium between Hg 0 and Hg 2+ caused by the the formation of a stable RS − −Hg 2+ conjugate.

Increased methylmercury toxicity related to obesity in diabetic KK-Ay mice

We examined the toxic effects of methylmercury (MeHg) in KK‐Ay type 2 diabetic mice to clarify how metabolic changes associated with type 2 diabetes mellitus affect MeHg toxicity. MeHg (5 mg Hg kg –1day–1 p.o.) was given to 4‐week‐old male KK‐Ay and C57BL/6J (BL/6) mice three times per week for 6 weeks. Average body weights (BW) of vehicle‐treated BL/6 and KK‐Ay mice were 16.3 and 16.4 g respectively on the first day, and 24.8 and 42.3 g respectively on the last day of the experiment. MeHg‐treated KK‐Ay mice began to lose weight about 5 weeks after MeHg administration. Six of seven MeHg‐treated KK‐Ay mice showed hind‐limb clasping in the final stage of the experiment. The mean blood mercury level of MeHg‐treated KK‐Ay mice reached a maximum of 9.8 µg ml–1, whereas that of the MeHg‐treated BL/6 mice was 2.8 µg ml–1 after 10 days of treatment. The average total mercury concentrations in the cerebrum and epididymal fat pad were 7.4 and 0.57 µg g–1, respectively, for BL/6 mice and 27 and 1.6 µg g–1, respectively, for KK‐Ay mice. In MeHg‐treated KK‐Ay mice with neurological symptoms, CD204‐positive macrophages were observed in the brain, kidney and spleen, indicating CD204 could be a marker for injured tissues. BW loss and significant pathological changes were not observed in other groups of mice. These results indicate that body fat gain in type 2 diabetes mellitus and low mercury accumulation in adipose tissue increased MeHg concentrations in organs and enhanced toxicity in KK‐Ay mice at the same dose of MeHg per BW. Copyright

Implications of mercury concentrations in umbilical cord tissue in relation to maternal hair segments as biomarkers for prenatal exposure to methylmercury

In this study, we investigated how mercury (Hg) concentrations in umbilical cord tissue are correlated with those in biomarkers for prenatal exposure to methylmercury (MeHg). Total Hg (T-Hg) concentrations were measured in 54 mother-child paired samples of maternal blood, umbilical cord tissue, cord blood, and maternal hair segments (1-cm incremental segments from the scalp) collected at parturition. MeHg concentrations were also measured in the cord tissue. Median T-Hg and MeHg concentrations in cord tissue on a dry-weight basis (d.w.) were 62.2ng/g and 56.7ng/g, respectively. Proportions of MeHg to T-Hg were approximately 95%. Both T-Hg and MeHg in cord tissue (d.w.) showed better correlations with T-Hg in cord blood than did T-Hg in cord tissue on a wet-weight basis (w.w.). Median T-Hg concentrations in maternal blood, cord blood, and maternal hair (0-1cm from the scalp) were 3.79ng/g, 7.26ng/g, and 1.35 μg/g, respectively. Median T-Hg concentration in cord blood was 1.92 times higher than that in maternal blood. T-Hg in cord tissue (d.w.) showed a strong correlation with that in cord blood (r=0.912, p<0.01). Among the hair segments, T-Hg in cord tissue (d.w.) showed the strongest correlation (r=0.854, p<0.01) with that in maternal hair at 0-1cm from the scalp, reflecting growth for approximately 1 month before parturition. Based on the present results, T-Hg and MeHg concentrations in cord tissue may be useful biomarkers for prenatal MeHg exposure of the fetus, especially reflecting the maternal MeHg body burden during late gestation. The conversion factors for T-Hg and MeHg concentrations in cord tissue (d.w.) to T-Hg concentrations in maternal hair (0-1cm from the scalp) were calculated to be 22.37 and 24.09, respectively. This information will be useful for evaluating maternal MeHg exposure levels in retrospective studies using preserved umbilical cord tissue.

Stimulation of elemental mercury oxidation by SH compounds

Anthropogenic mercury pollution has been a serious environmental problem. The presence of mercury in the environment has received a great deal of attention due to its highly toxic nature and translocation through the food chain. Elemental mercury released into the Amazon River basin due to gold mining activities is roughly estimated at 130 tons per year. In fact, high levels of total mercury, mostly in the form of methylmercury, in fish collected from around the gold mining areas and high levels of methylmercury in the hair of humans living in fishing villages downstream of these areas have recently been documented. These results suggest that the reaction which converts the discharged elemental mercury into mercuric mercury is present in nature before the methylation of the generated mercuric mercury. Methylation and reduction of mercuric mercury and decomposition of organomercury have been extensively studied. However, little information is available concerning the conversion of elemental mercury in aquatic ecosystems. The purpose of this study was to clarify the mechanism of oxidation of elemental mercury to mercuric mercury in the aquatic environment. 11 refs., 4 figs.

Proteomic Analysis of Cerebellum in Common Marmoset Exposed to Methylmercury

The cerebellum is known as the major target regions of methylmercury (MeHg) toxicity, but the mechanisms are still not fully understood. We studied the effects of MeHg exposure in the cerebellum of common marmoset (Callithrix jacchus) using a shotgun proteomic approach with liquid chromatography coupled to mass spectrometry. A total of 1000 common proteins were identified in all samples, and 102 proteins were significantly differentially expressed in the cerebellum of common marmoset with orally dosed MeHg (1.5 mg MeHg/kg body weight for 2 weeks) compared with those of the control group. Functional enrichment analysis and pathway predictions showed that the differentially expressed proteins were involved in carbohydrate derivative metabolic process, ion transport including synaptic transmission, cell development, and calcium signaling pathway. Cellular component enrichment analysis showed that they were mainly distributed in plasma membrane, excitatory synapse, and synaptic membrane. These results indicate that synaptic transmission and calcium signaling pathways are the core functions affected by MeHg. We found a total of 21 novel proteins affected by MeHg in synaptic transmission and calcium signaling pathways. DLG4: (PSD95) and MIR-19A/MIR-19B were found to be potential key targets leading to the multiple effects of MeHg neurotoxicity. These results show the global effects of MeHg on cellular functions and pathways leading to neurological deficits in common marmoset.

Suppression of methylmercury-induced IL-6 and MCP-1 expressions by N-acetylcysteine in U-87MG human astrocytoma cells

AIMS The aim of this study was to clarify the involvement of oxidative stress in methylmercury (MeHg)-induced pro-inflammatory cytokine expressions and the suppressive effects of N-acetylcysteine (NAC) in MeHg-induced cytokine expression. MATERIALS AND METHODS Using U-87-MG human astrocytoma cell line, interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 expressions induced by 4 μM MeHg were measured at mRNA and protein levels. Hydrogen peroxide (H2O2) and superoxide anion (O2(-)) were quantified by flow-cytometry analysis. To examine the suppressive effects of NAC on the cytokine expressions among different timing of NAC treatment, cells were treated with 0.5 or 5mM NAC before, simultaneously, or after MeHg administration. KEY FINDINGS MeHg exposure at 4 μM, a non-cytotoxic concentration, significantly induced MCP-1 and IL-6 expressions at both mRNA and protein levels. A significant increase of H2O2 production but not O2(-) was observed. MeHg-induced expression of MCP-1 and IL-6 mRNA was reduced by 10-20% in the presence of 5mM NAC (co-treatment experiment) compared to cells treated with MeHg only. Pre-treatment of cells with 0.5 or 5mM NAC at 0.5 or 1h and its subsequent washout before MeHg addition suppressed MCP-1 and IL-6 cytokine expressions. Post-treatment of cells with NAC after MeHg addition also suppressed the cytokine induction, but the magnitude of suppression was evidently lower than in co-treated cells even though the H2O2 generation was almost completely suppressed by NAC. SIGNIFICANCE NAC may effectively suppress the MeHg-induced cytokine production through both, inhibition of reactive oxygen species as well as extracellular chelation of MeHg in astrocytes.