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1.
Biol Pharm Bull ; 44(4): 522-527, 2021.
Article En | MEDLINE | ID: mdl-33790104

Methylmercury (MeHg) exposure during pregnancy is a concern because of its potential health risks to fetuses. Intestinal microbiota has important roles in the decomposition and fecal excretion of MeHg. We investigated the effect of nondigestible saccharides on the accumulation and excretion of Hg after MeHg exposure. Female BALB/cByJ mice were fed a basal diet or the same diet supplemented with 5% fructooligosaccharides (FOS) or 2.5% glucomannan. Six weeks after feeding, mice were administered MeHg chloride (4 mg Hg/kg, per os (p.o.)), and urine and feces were collected for 28 d. FOS-fed mice had lower total Hg levels in all tissues (including the brain) compared with that of controls. The glucomannan diet had no effect on tissue Hg levels. No differences in tissue concentrations of inorganic Hg among groups were found. Fecal Hg excretion was markedly higher in FOS-fed mice than that in controls, but urinary Hg excretion was similar. FOS-fed mice had a higher proportion of inorganic Hg in feces than that of controls, with a significant increase in fecal Hg excretion. Analysis of fecal bacterial population showed the relative abundance of Bacteroides in FOS-fed mice to be higher than that in controls. The results suggest that FOS enhanced fecal Hg excretion and decreased tissue Hg levels after MeHg administration, possibly by accelerating MeHg demethylation by intestinal bacteria (the candidate genus Bacteroides). This demethylation also reduces MeHg absorption in the large intestine. In conclusion, daily FOS intake may decrease tissue Hg levels in animals and humans exposed to MeHg.


Brain/metabolism , Dietary Supplements , Mercury/metabolism , Methylmercury Compounds/pharmacokinetics , Oligosaccharides/pharmacology , Animals , Bacteria/genetics , Bacteria/isolation & purification , Feces/chemistry , Feces/microbiology , Female , Gastrointestinal Microbiome/drug effects , Kidney/metabolism , Liver/metabolism , Mannans/pharmacology , Methylmercury Compounds/blood , Mice, Inbred BALB C , RNA, Ribosomal, 16S
2.
Int Arch Occup Environ Health ; 94(3): 419-431, 2021 Apr.
Article En | MEDLINE | ID: mdl-33104857

OBJECTIVE: Depression is a highly-prevalent disorder among US adults and despite advancements in treatment options, prevalence rates are increasing. With the emerging recommendations of dietary interventions such as high fish intake come potential risks, for example, exposure to methylmercury (MeHg). Case reports and animal models have suggested a possible association of high doses of MeHg with psychiatric symptoms; the impact of low-dose exposure on depression remains unknown. METHODS: In this cross-sectional study, survey-weighted logistic regression models were built to assess the relationship between low-dose MeHg blood levels and depression in a sample of n = 3930 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. RESULTS: 9.1% (n = 1335) of the respondents screened positive for depression; all participants had MeHg blood levels below the US Environmental Protection Agency's reference dose. The adjusted multivariate logistic regression model showed no statistically significant association between MeHg blood levels and depression. CONCLUSION: Low-dose MeHg does not seem to be associated with depression in this study. However, dietary recommendations with regards to fish intake should be made cautiously. Further studies are needed, especially considering predicted increasing environmental pollution of our food webs and the potentially higher vulnerability of subpopulations such as pregnant women.


Depression/epidemiology , Environmental Exposure , Environmental Pollutants/blood , Methylmercury Compounds/blood , Adult , Aged , Aged, 80 and over , Animals , Female , Fishes , Food Contamination , Humans , Male , Middle Aged , Nutrition Surveys , Risk , United States , Young Adult
3.
Neurotoxicology ; 81: 1-10, 2020 12.
Article En | MEDLINE | ID: mdl-32735808

Developmental methylmercury (MeHg) exposure can have lasting consequences on neural development and motor function across the lifespan. Recent evidence for MeHg targeting of myogenic pathways has drawn attention to the possibility that developing skeletal muscle plays a role in the motor deficits stemming from early life MeHg exposure. In this study we examined a potential role for muscle in influencing MeHg developmental toxicity in offspring of female mice exposed to MeHg via drinking water. Dams had access to 0, 0.5 or 5.0 ppm MeHg chloride in drinking water from two weeks prior to mating through weaning. Blood, brain and muscle tissue was harvested from dams at weaning and pups at postnatal days (PND) 6, 21 and 60 for analysis of total Hg. Muscle tissue sections were examined with histological stains. Behavioral testing of offspring was conducted at PND 60 and included locomotor activity, inverted screen, grip strength and rotarod tests to assess motor function. Total Hg (tHg) levels in dam muscles at weaning were 1.7-3-fold higher than Hg levels in blood or brain. In PND6 male and female pups, muscle and brain tHg levels were 2 to 4-fold higher than blood tHg. Brain tHg levels decreased more rapidly than muscle tHg levels between PND 6 and 21. Premised on modeling of growth dilution, brain tissue demonstrated an elimination of tHg while muscle tissue exhibited a net uptake of tHg between PND 6 and 21. Despite overall elevated Hg levels in developing muscle, no gross morphological or cytological phenotypes were observed in muscle at PND 60. At the higher MeHg dose, grip strength was reduced in both females and males at PND 60, whereas only male specific deficits were observed in locomotor activity and inverted screen tests with marginally significant deficits on rotarod. These findings highlight a potential role for developing skeletal muscle in mediating the neuromuscular insult of early life MeHg exposure.


Mercury Poisoning, Nervous System/physiopathology , Methylmercury Compounds , Motor Activity , Muscle, Skeletal/growth & development , Prenatal Exposure Delayed Effects , Age Factors , Animals , Body Burden , Brain/metabolism , Disease Models, Animal , Female , Gestational Age , Hand Strength , Locomotion , Male , Maternal Exposure , Mercury Poisoning, Nervous System/etiology , Mercury Poisoning, Nervous System/metabolism , Methylmercury Compounds/blood , Mice, Inbred C57BL , Muscle, Skeletal/metabolism , Pregnancy , Rotarod Performance Test , Sex Factors
4.
J Nutr ; 150(7): 1749-1756, 2020 07 01.
Article En | MEDLINE | ID: mdl-32433731

BACKGROUND: Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. OBJECTIVE: Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. METHODS: From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. RESULTS: In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, ß = 0.205, P = 0.03; TC compared with CC, ß = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, ß = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, ß = 0.109, P = 0.04). CONCLUSIONS: In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.


Fatty Acid Desaturases/metabolism , Fatty Acids, Unsaturated/blood , Fishes , Methylmercury Compounds/blood , Animals , Child Development , Delta-5 Fatty Acid Desaturase , Fatty Acid Desaturases/genetics , Female , Food Contamination , Gene Expression Regulation, Enzymologic , Genotype , Humans , Infant , Infant, Newborn , Male , Methylmercury Compounds/toxicity , Mothers , Seychelles , Water Pollutants, Chemical/blood , Water Pollutants, Chemical/toxicity
5.
Forensic Sci Med Pathol ; 16(3): 504-509, 2020 09.
Article En | MEDLINE | ID: mdl-32323188

We report a rare case of fatal intoxication in a 40-year-old man caused by injection of a fluid containing organic mercury, allegedly in an attack with a syringe fixed to the tip of an umbrella. The man suffered from severe neurological symptoms and progressive multiorgan failure and died 10 months later in refractory status epilepticus. Autopsy revealed severe brain atrophy and non-specific kidney damage. Neuropathological examination showed neuronal loss especially in the occipital lobe, distinct granule cell necrosis in the cerebellum and Wallerian degeneration in the brainstem. Postmortem toxicological analysis revealed extremely increased levels of mercury in liver and kidney tissue as well as methylmercury levels in peripheral blood.


Mercury Poisoning, Nervous System/diagnosis , Adult , Atrophy , Brain/pathology , Humans , Injections , Kidney/chemistry , Liver/chemistry , Male , Mercury/analysis , Methylmercury Compounds/blood
6.
J Expo Sci Environ Epidemiol ; 30(3): 504-514, 2020 05.
Article En | MEDLINE | ID: mdl-32015433

Fish/seafood consumption is a source of mercury; other dietary sources are not well described. This cross-sectional study used National Health and Nutrition Examination Survey (NHANES) 2011-2012 data. Participants self-reported consuming fish/seafood (N = 5427) or not (N = 1770) within the past 30 days. Whole blood total mercury (THg), methylmercury (MeHg), and urinary mercury (UHg) were determined. Diet was assessed using 24 h recall. Adjusted regression models predicted mercury biomarker concentrations with recent food consumption, while controlling for age, sex, education, and race/ethnicity. Geometric mean THg was 0.89 µg/L (95% confidence interval (CI): 0.78, 1.02) (seafood consumers) and 0.31 µg/L (95% CI: 0.28, 0.34) (non-seafood consumers); MeHg and UHg concentrations follow similar patterns. In adjusted regressions among seafood consumers, significant associations were observed between mercury biomarkers with multiple foods, including fish/seafood, wine, rice, vegetables/vegetable oil, liquor, and beans/nuts/soy. Among non-seafood consumers, higher THg was significantly associated with mixed rice dishes, vegetables/vegetable oil, liquor, and approached statistical significance with wine (p < 0.10); higher MeHg was significantly associated with wine and higher UHg was significantly associated with mixed rice dishes. Fish/seafood consumption is the strongest dietary predictor of mercury biomarker concentrations; however, consumption of wine, rice, vegetables/vegetable oil, or liquor may also contribute, especially among non-seafood consumers.


Food Contamination/statistics & numerical data , Nutrition Surveys , Seafood/statistics & numerical data , Adult , Animals , Biomarkers/metabolism , Cross-Sectional Studies , Diet , Female , Food Contamination/analysis , Humans , Male , Mercury/blood , Methylmercury Compounds/blood , Oryza , Vegetables , Wine
7.
J Trace Elem Med Biol ; 57: 60-67, 2020 Jan.
Article En | MEDLINE | ID: mdl-31563817

BACKGROUND: The main exposure route to methylmercury (MeHg) is from eating fish and shellfish containing this compound. Since 2004, women of childbearing age in Spain have been urged not to eat some species (eg, tuna, shark, and swordfish), instead choosing low-MeHg seafood as part of a healthy diet. OBJECTIVE: To describe maternal total blood mercury (THg) and serum selenium (Se) in a cohort of pregnant women living in Spain as it relates to fish intake during the three trimesters and to assess whether or not Spanish women of childbearing age follow the recommendations listed in fish advisories and choose fish species with lower mercury levels. METHODS: We studied 141 female volunteers of childbearing age (16-45 years), interviewing all participants about their overall eating habits and seafood intake. Hg and Se levels were tested using cold-vapor atomic absorption spectrometry (CVAAS) and electrothermal atomic absorption spectrometry (ETAAS), respectively. RESULTS: Average THg levels in pregnant women were 2.89 µg/L (standard deviation [SD], 2.75 µg/L, geometric mean [GM], 2.19 µg/L), and THg GM was positively associated with fish intake. Mean Se levels in pregnant women were 73.06 µg/L (SD, 13.38 µg/L), and Se levels were found to increase with tuna intake. In 16 (12%) pregnant women, THg was higher than the level recommended by the U.S. Environmental Protection Agency (EPA) (6.4 µg/L). A positive association was also found between THg and serum Se. CONCLUSION: Women of childbearing age in Spain had higher THg levels than women in other Western studies. Our study observed that 12% of women had THg levels above the safety limit set by the EPA (6.4 µg/L), and 31% had levels above the relevant benchmark level of 3.5 µg/L suggested by various researchers.


Mercury/blood , Selenium/blood , Adolescent , Adult , Female , Humans , Methylmercury Compounds/blood , Middle Aged , Pregnancy , Spain , Young Adult
8.
Article En | MEDLINE | ID: mdl-31812836

We developed and validated a liquid chromatography-inductively coupled plasma mass spectrometry (LC-ICP-MS) method for simultaneous determination of methylmercury (MeHg) and inorganic mercury (I-Hg) in human blood samples. Thallium was used as an internal standard for determination of MeHg and 196Hg was used as an internal standard for I-Hg determination. The blood samples were extracted using a 7% (v/v) HCl solution containing 1.5% (w/v) l-cysteine. A 10% (w/v) trichloroacetic acid solution was used to precipitate proteins in the extract. Mercury species were measured by LC-ICP-MS. The linear range of the assay was 0.08-60  ng/mL for MeHg and 0.05-2.5 ng/mL for I-Hg. The method was validated with the Certified Reference Materials Blood Mercury (Institut National de Santé Publique Québec, Quebec, Canada) and Seronorm™ Trace Elements Whole Blood (Sero AS, Billingstad, Norway). Additional validation was performed by comparing the results obtained with those from a widely used gas chromatography method with electron-capture detection. The proposed method was applied to the simultaneous determination of MeHg and I-Hg in human blood samples. The LC-ICP-MS method provides precise, accurate, and robust determination of MeHg and I-Hg levels in human blood over a long period and has a simple and quick sample preparation. We expect that this method will contribute to large-scale evaluation of human exposure to mercury compounds in future.


Chromatography, Liquid/methods , Mass Spectrometry/methods , Mercury/blood , Methylmercury Compounds/blood , Adult , Animals , Female , Humans , Limit of Detection , Linear Models , Male , Middle Aged , Reproducibility of Results , Young Adult
9.
Environ Res ; 177: 108627, 2019 Oct.
Article En | MEDLINE | ID: mdl-31421448

In recent years, several studies have addressed the issue of prenatal exposure to methylmercury (MeHg); however, few have actually analysed MeHg blood concentrations. Our study population included mothers and their new-borns from Slovenia (central region; N = 584) and Croatia (coastal region; N = 234). We have measurements of total Hg (THg) and MeHg in maternal hair, maternal peripheral blood, and cord blood. Cord blood Hg concentrations were low to moderate (median THg = 1.84 ng/g and MeHg = 1.69 ng/g). The proportion of THg as MeHg (%MeHg) in maternal and cord blood varied between 4% and 100% (coefficient of variation, CV = 32%) and between 8% and 100% (CV = 20%), respectively. Our data shows that variability of %MeHg was higher at lower blood THg levels. Concentrations of MeHg in maternal blood and cord blood were highly correlated (Rs = 0.943), in the case of inorganic Hg correlation was significant but weaker (Rs = 0.198). MeHg levels in maternal blood and cord blood were positively associated with seafood intake, maternal age, and negatively associated with pre-pregnancy BMI. Additionally, MeHg in maternal blood was positively associated with plasma selenium levels, and cord blood MeHg was negatively associated with parity. The results of multiple linear regression models showed that speciation analysis provides more defined estimation of prenatal exposure in association modelling. Associations between Hg exposure and cognitive performance of children (assessed using Bayley Scales of Infant and Toddler development) adjusted for maternal or child Apolipoprotein E genotypes showed higher model R2 and lower p-values when adjusted for MeHg compared to THg. This study demonstrates that Hg speciation improves the association between exposure and possible negative health effects.


Maternal Exposure , Mercury/blood , Methylmercury Compounds/blood , Croatia , Female , Fetal Blood , Humans , Infant, Newborn , Pregnancy , Slovenia
10.
Int J Circumpolar Health ; 78(1): 1642090, 2019 12.
Article En | MEDLINE | ID: mdl-31339476

The objective of this study was to identify geographic, dietary, and other predictors for childhood exposure to perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), and methylmercury in Greenlandic children. The study includes cross-sectional data from 367 Greenlandic children aged 7 to 12 years examined during 2012-2015. A parent or guardian participated in a structured interview, and a blood sample from the child was analysed for PFASs, PCBs and total mercury. Predictors for the environmental exposures were identified using linear regression. Area of residence was found to have the strongest explanatory power, accounting for 24% to 68% of the variance in the serum concentrations. Information about diet was available for two-thirds of the children, and among these, consumption of traditional Greenlandic food accounted for 2% to 10% of the variance in the biomarker concentrations. Models including all predictors associated with at least one of the environmental chemicals explained 19% to 54% of the total variance. In conclusion, area is a likely proxy for a traditional marine diet, and together area and diet constitute the most important predictors of exposure to methylmercury, PCBs and PFASs among Greenlandic children.


Diet/statistics & numerical data , Environmental Exposure/statistics & numerical data , Child , Diet/adverse effects , Environmental Exposure/adverse effects , Environmental Pollutants/adverse effects , Environmental Pollutants/blood , Female , Fluorocarbons/adverse effects , Fluorocarbons/blood , Geography , Greenland/epidemiology , Humans , Male , Methylmercury Compounds/adverse effects , Methylmercury Compounds/blood , Polychlorinated Biphenyls/adverse effects , Polychlorinated Biphenyls/blood
11.
Sci Total Environ ; 676: 268-277, 2019 Aug 01.
Article En | MEDLINE | ID: mdl-31048158

Using the blood of grey seal pups, the blood and milk of female grey seals inhabiting the Hel Marine Station of Gdansk University's Institute of Oceanography (HMS), we monitored the transfer of total mercury (THg), methylmercury (MeHg), and selenium (Se) with blood during foetal life and nursing. Changes in the concentration of mercury and selenium were characterised in the pups' blood during their first three months of life when they transition from suckling, to a post-weaning fast, to eating fish. In the blood of pregnant females, there was a significant decrease in THg and MeHg concentrations throughout the gestation, indicating the transfer of these toxins through the placenta into the foetus. At no other stage of the pup's development was there such a high level of THg and MeHg as on the day of birth, despite the incorporation of mercury into the lanugo during foetal growth. This suggests that the maternal transfer of mercury during gestation may be the time of greatest mercury exposure for a young seal pup. The consumption of milk caused a rapid increase in weight and a lowering of the mercury level in the blood in the subsequent days of the pups' life. The postweaning fast was the period of the lowest mercury concentration. The switch to a diet consisting of fish caused a systematic increase in the concentration of mercury in the blood of the pups. Milk was the significant source of selenium for pups and the selenium concentration in females' blood was reduced during lactation. The nursing period seemed to have the greatest impact on the mercury and selenium blood levels in examined seals. Natural development of the grey seal pup created an opportunity to decrease the levels of toxic substances obtained through the maternal transfer during foetal growth.


Environmental Monitoring , Methylmercury Compounds/blood , Seals, Earless/blood , Selenium/blood , Water Pollutants, Chemical/blood , Animals , Baltic States , Female , Mercury/metabolism , Milk/metabolism
12.
Environ Int ; 124: 278-283, 2019 03.
Article En | MEDLINE | ID: mdl-30660840

BACKGROUND: Fish contains methylmercury (MeHg) which can cause oxidative stress and neurodevelopmental toxicity at sufficiently high doses. Fish also contains polyunsaturated fatty acids (PUFA) which have both antioxidant (n-3) and oxidant (n-6) properties. Mitochondrial DNA (mtDNA) is sensitive to oxidative stress but has not been previously studied in relation to MeHg exposure or PUFA status. OBJECTIVE: To investigate the associations between MeHg exposure and PUFA status during pregnancy with relative mitochondrial DNA copy number (RmtDNAcn) in mothers and their newborns. METHODS: In total, 1488 mother-child pairs from the Seychelles Child Development Study Nutrition Cohort 2 were included in this study. Total Hg was measured in maternal blood collected at 28 weeks' gestation, maternal hair at delivery, and in fetal cord blood. PUFA (n-3 and n-6) were measured only in maternal blood. RmtDNAcn was measured by qPCR in both maternal and cord blood. RESULTS: Increasing maternal blood Hg (ß = 0.001, 95%CI: 0.000, 0.002) and n-3 PUFA concentrations (ß = 0.183, 95%CI: 0.048, 0.317) were associated with higher maternal RmtDNAcn. Increasing maternal n-6 PUFA (ß = -0.103, 95%CI: -0.145, -0.062) and n-6/n-3 ratio (ß = -0.011, 95%CI: -0.017, -0.004) were associated with lower maternal RmtDNAcn. Increasing fetal cord blood Hg was associated with lower fetal RmtDNAcn (ß = -0.002, 95%CI: -0.004, -0.000). Neither maternal blood Hg nor PUFA status was associated with fetal RmtDNAcn. CONCLUSIONS: Our findings suggest that MeHg and PUFA may influence mitochondrial homeostasis although the magnitude of these associations are small. Future studies should confirm the findings and explore the underlying mechanisms.


Child Development , DNA, Mitochondrial/drug effects , Fatty Acids, Omega-3/blood , Methylmercury Compounds/blood , Adult , Animals , Cohort Studies , Female , Fetal Blood , Fishes , Humans , Infant, Newborn , Male , Mothers , Nutritional Status , Pregnancy , Seafood/analysis , Seychelles
13.
Environ Sci Pollut Res Int ; 26(3): 2445-2454, 2019 Jan.
Article En | MEDLINE | ID: mdl-30471058

Mercury and lead are deposited in the West Carpathians as long-range transported air pollution. The Alpine accentor (Prunella collaris) was recognized as a cost-effective biomonitor, and used to investigate the bioavailability of contaminants in large alpine areas. The outer tail feathers and blood of the alpine accentors were used for assessment of atmospheric mercury and lead contamination, respectively. Mean mercury levels in feathers of accentors averaged at 1.15 µg/g (SE = 0.105, n = 40). There were no temporal variations in mercury concentrations. Mean blood lead levels were at 5.2 µg/dL (SE = 0.5, n = 27), showing a slight decreasing trend from July to October. Juveniles were not more susceptible to lead accumulation than adults. Bone lead concentrations that increase with age reflect a bioaccumulation effect. A statistically significant negative correlation was found between the length of erythrocytes and the concentration of lead, which may show the first symptoms of microcytosis. In comparison to aquatic ecosystems, the biogeochemical factors that influence methylmercury availability in alpine habitats are not yet completely known and require further investigation. Our findings show that birds in alpine terrestrial ecosystems may contain surprisingly high levels of methylmercury. The mercury levels in the feathers of accentors probably indicate that alpine autotrophs make sufficient amounts of mercury available to the terrestrial food web. The blood lead levels of accentors likely approach the threshold level for further hematological effects. We found a clear tendency in erythrocytes to change their shape from ellipsoid to smaller and rounder with increasing amounts of lead in their blood. The shape of bird erythrocytes appears to be a very sensitive indicator of critical levels of lead in the alpine environment.


Birds/blood , Lead/analysis , Methylmercury Compounds/analysis , Air Pollution , Animals , Ecosystem , Environmental Monitoring , Feathers/chemistry , Food Chain , Lead/blood , Methylmercury Compounds/blood
14.
J Appl Toxicol ; 39(2): 221-230, 2019 02.
Article En | MEDLINE | ID: mdl-30175511

Methylmercury (MeHg) is known to cause neurobehavioral impairment in human and experimental animals. We previously reported that MeHg (5 mg Hg/kg) induced severe neurobehavioral dysfunction in 4-week-old KK-Ay mice, although it is difficult to evaluate quantitatively the neurobehavioral impairment in MeHg-treated KK-Ay mice because of their obesity. The aim of this study was to evaluate MeHg-induced neurobehavioral dysfunction in KK-Ay mice using the dynamic weight-bearing test, which analyzes the animal's weight distribution between the four limbs. Male 12-week-old KK-Ay mice were treated with MeHg (5 mg Hg/kg) three times per week for 5 weeks. Body weight loss began after approximately 2 weeks of MeHg treatment, and decreased significantly at 4 weeks. Seven of the nine MeHg-treated mice exhibited overt neurological symptoms such as ataxia and gait disturbance. The weight-bearing load was lower for the forelimb than for the hindlimb at baseline and until 1 week after MeHg treatment was initiated. In weeks 2-4, the dynamic weight-bearing loads on the forelimb and hindlimb were similar. The load on the forelimb exceeded the load on the hindlimb after 5 weeks of treatment. This finding indicates that the dynamic weight-bearing test is useful for semi-quantitative evaluation of neurobehavioral impairment in MeHg-treated rodents, and is less stressful for the animals. Infiltration of CD204-positive macrophages was observed in the sciatic nerve of MeHg-treated mice, suggesting that CD204 can serve as a useful marker of tissue injury in peripheral nerves and a possible target in regenerating peripheral nerves and controlling neuropathies.


Behavior, Animal/drug effects , Mercury Poisoning, Nervous System/physiopathology , Methylmercury Compounds/toxicity , Motor Activity/drug effects , Weight-Bearing/physiology , Animals , Brain/drug effects , Brain/metabolism , Male , Mercury Poisoning, Nervous System/blood , Mercury Poisoning, Nervous System/urine , Methylmercury Compounds/blood , Methylmercury Compounds/urine , Mice , Mice, Inbred Strains , Sciatic Nerve/drug effects , Sciatic Nerve/metabolism
15.
Comput Math Methods Med ; 2018: 2509413, 2018.
Article En | MEDLINE | ID: mdl-30046350

Methylmercury is widely known to be a toxic substance in the human, especially a nervous system. However, it is difficult to accurately measure the amount of methylmercury in blood, and the form of methylmercury is variously presented. The purpose of study was to compare the total mercury and methylmercury measurements techniques and detection levels between analytical institutions in two countries using the same elderly human blood samples. Total mercury using gold amalgamation direct mercury analysis method (both) and methylmercury using the dithizone extraction and gas chromatography-electron capture detector (GC-ECD) method (N Lab in Japan) and the cold vapor atomic fluorescence spectrophotometer (CVAFS) method (D Lab in Korea) were measured in 47 subjects who agreed to participate in this study. Total mercury concentrations in both analytical laboratories were observed at similar levels (9.4 versus 9.5 ug/kg, p=0.898) and the distribution was highly correlated. However, the concentration of methylmercury showed some difference between two laboratories (9.1 versus 8.6 ug/kg, p<0.001). Due to different recovery rates by different analytical methods, it is assumed that the methyl/total mercury ratio in N lab in Japan was higher than D lab in Korea (96.8 versus 90.4%, p<0.001). The GC-ECD was more sensitive method than CVAFS in methylmercury analytic techniques.


Methylmercury Compounds/blood , Aged , Female , Hematologic Tests , Humans , Japan , Male , Reference Values , Republic of Korea
16.
Ecotoxicol Environ Saf ; 162: 603-615, 2018 Oct 30.
Article En | MEDLINE | ID: mdl-30031321

Ubiquitous low-dose methylmercury (MeHg) exposure through an increased fish consumption represents a global public health problem, especially among pregnant women. A plethora of micronutrients presented in fish affects MeHg uptake/distribution, but limited data is available. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. Therefore, the present study aimed to examine the effects of both MeHg and retinyl palmitate administered on pregnant and lactating rats in metabolic and redox parameters from dams and their offspring. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/kg/day) and retinyl palmitate (7500 µg RAE/kg/day) via gavage, either individually or in combination from the gestational day 0 to weaning. For dams (150 days old) and their offspring (31 days old), glycogen accumulation (hepatic and cardiac) and retinoid contents (plasma and liver) were analyzed. Hg deposition in liver tissue was quantified. Redox parameters (liver, kidney, and heart) were evaluated for both animals. Cytogenetic damage was analyzed with micronucleus test. Our results showed no general toxic or metabolic alterations in dams and their offspring by MeHg-VitA co-administration during pregnancy and lactation. However, increased lipoperoxidation in maternal liver and a disrupted pro-oxidant response in the heart of male pups was encountered, with apparently no particular effects in the antioxidant response in female offspring. GST activity in dam kidney was altered leading to possible redox disruption of this tissue with no alterations in offspring. Finally, the genomic damage was exacerbated in both male and female pups. In conclusion, low-dose MeHg exposure and retinyl palmitate supplementation during gestation and lactation produced a potentiated pro-oxidant effect, which was tissue-specific. Although this is a pre-clinical approach, we recommend precaution for pregnant women regarding food consumption, and we encourage more epidemiological studies to assess possible modulations effects of MeHg-VitA co-administration at safe or inadvertently used doses in humans, which may be related to specific pathologies in mothers and their children.


Antioxidants/pharmacology , Lactation , Methylmercury Compounds/toxicity , Vitamin A/analogs & derivatives , Animals , Animals, Newborn , Catalase/metabolism , Dietary Supplements , Diterpenes , Female , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Liver/drug effects , Liver/metabolism , Male , Methylmercury Compounds/blood , Oxidation-Reduction/drug effects , Pregnancy , Prenatal Exposure Delayed Effects , Rats , Rats, Wistar , Retinyl Esters , Superoxide Dismutase/metabolism , Vitamin A/blood , Vitamin A/metabolism , Vitamin A/pharmacology
17.
Sci Rep ; 8(1): 8865, 2018 06 11.
Article En | MEDLINE | ID: mdl-29891979

Seabirds are widely used as bioindicators of mercury (Hg) contamination in marine ecosystems and the investigation of their foraging strategies is of key importance to better understand methylmercury (MeHg) exposure pathways and environmental sources within the different ecosystems. Here we report stable isotopic composition for both Hg mass-dependent (e.g. δ202Hg) and mass-independent (e.g. Δ199Hg) fractionation (proxies of Hg sources and transformations), carbon (δ13C, proxy of foraging habitat) and nitrogen (δ15N, proxy of trophic position) in blood of four species of sympatric penguins breeding at the subantarctic Crozet Islands (Southern Indian Ocean). Penguins have species-specific foraging strategies, from coastal to oceanic waters and from benthic to pelagic dives, and feed on different prey. A progressive increase to heavier Hg isotopic composition (δ202Hg and Δ199Hg, respectively) was observed from benthic (1.45 ± 0.12 and 1.41 ± 0.06‰) to epipelagic (1.93 ± 0.18 and 1.77 ± 0.13‰) penguins, indicating a benthic-pelagic gradient of MeHg sources close to Crozet Islands. The relative variations of MeHg concentration, δ202Hg and Δ199Hg with pelagic penguins feeding in Polar Front circumpolar waters (1.66 ± 0.11 and 1.54 ± 0.06‰) support that different MeHg sources occur at large scales in Southern Ocean deep waters.


Environmental Monitoring , Mercury/metabolism , Methylmercury Compounds/metabolism , Spheniscidae/metabolism , Water Pollutants, Chemical/analysis , Animals , Carbon Isotopes/blood , Ecosystem , Environmental Biomarkers , Feeding Behavior , Food Chain , Indian Ocean , Mercury/blood , Methylmercury Compounds/blood , Nitrogen Isotopes/blood , Species Specificity
18.
Environ Int ; 117: 125-131, 2018 08.
Article En | MEDLINE | ID: mdl-29738916

BACKGROUND: Although biologically plausible, epidemiological evidence linking exposure to methylmercury with increased risk of ischemic stroke is limited. The effects of methylmercury may be modified by selenium, which is an anti-oxidant that often co-exists with mercury in fish. OBJECTIVES: To examine the association between serum mercury levels with the incidence of ischemic stroke and to explore the possible effect modifications by serum selenium levels and demographic and geographic factors. METHODS: A case-cohort study was designed nested in the REasons for Geographic and Racial Differences in Stroke cohort, including 662 adjudicated incident cases of ischemic stroke and 2494 participants in a randomly selected sub-cohort. Serum mercury was measured using samples collected at recruitment. Multivariable-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were estimated using the Barlow-weighting method for the Cox proportional hazards regression model. RESULTS: No statistically significant association was observed between serum mercury concentration and the incidence of ischemic stroke (the highest vs. lowest quintile of mercury levels: HR = 0.82; 95% CI = 0.55-1.22; P for linear trend = 0.42). Sex (P for interaction = 0.06), but not serum selenium levels, modified the association; a more evident trend toward lower incidence of ischemic stroke with higher mercury levels was observed among women. CONCLUSION: This study does not support an association between mercury and the incidence of ischemic stroke within a population with low-to-moderate level of exposure. Further studies are needed to explore the possibility of mercury-induced ischemic stroke toxicity in other populations at higher exposure levels.


Brain Ischemia , Methylmercury Compounds/blood , Stroke , Brain Ischemia/blood , Brain Ischemia/epidemiology , Cohort Studies , Female , Humans , Male , Selenium/blood , Stroke/blood , Stroke/epidemiology
19.
Int J Circumpolar Health ; 77(1): 1474706, 2018 12.
Article En | MEDLINE | ID: mdl-29785879

To describe exposure to methylmercury among Cree, focusing on women of childbearing age, we used data from 2 studies. Multiple regression was employed to examine associations between blood and hair mercury concentrations and consumption of locally harvested fish. Approximately 9.9% of non-pregnant women aged 15-44 y and 3.9% of pregnant women required follow-up according to Health Canada's blood mercury guidance value of 40 nmol/L. 8% of hair mercury observations in the non-pregnant women and 2.5% among pregnant women exceeded the equivalent threshold of 10 nmol/g. The geometric mean blood mercury concentration was 12.7 nmol/L in 1,429 persons aged 8 and over, and 17.7 nmol/L in adults aged 18 and older. The proportion of hair mercury concentrations greater than 12.5 nmol/g decreased in all age-sex groups when comparing the 2002-2009 data to published values for 1993-1994. Among women of childbearing age, local fish consumption was associated with increased blood and hair mercury concentrations. While over 90% of women of childbearing age in this population have acceptable levels of mercury, ongoing intake of mercury suggests that their consumption of fish with known high mercury content be minimised. Reducing consumption of fish known to be high in mercury content needs to be balanced with promoting ongoing connection to Cree culture and land-based activities that are also important determinants of health.


Diet/statistics & numerical data , Fishes , Hair/chemistry , Indians, North American/statistics & numerical data , Mercury/analysis , Methylmercury Compounds/analysis , Prenatal Exposure Delayed Effects/etiology , Adolescent , Adult , Animals , Child , Child, Preschool , Diet/adverse effects , Female , Humans , Male , Mercury/blood , Methylmercury Compounds/blood , Pregnancy , Prenatal Exposure Delayed Effects/epidemiology , Quebec/epidemiology , Young Adult
20.
J Expo Sci Environ Epidemiol ; 28(5): 494-504, 2018 09.
Article En | MEDLINE | ID: mdl-29670220

BACKGROUND: Maternal blood total mercury (THg) is a biomarker for prenatal methylmercury (MeHg) exposure. Few studies have quantified both blood THg and MeHg during pregnancy, and few studies have reported longitudinal trends. OBJECTIVES: We analyzed blood THg and MeHg in a cohort of pregnant mothers in Charleston, South Carolina (n = 83), and investigated whether blood THg or MeHg changed between early and late gestation. METHODS: THg and MeHg were analyzed in blood samples from early (12 ± 1.7 weeks) and late (35 ± 2.2 weeks) gestation. RESULTS: Blood %MeHg (of THg) averaged 63% (range: 10-114%) and 61% (range: 12-117%) during early and late gestation, respectively. In unadjusted analyses, blood MeHg decreased from early to late pregnancy (paired t-test, p = 0.04), while THg did not change (paired t-test, p = 0.34). When blood MeHg was normalized by the hematocrit, this decrease was no longer statistically significant (paired t-test, p = 0.09). CONCLUSIONS: In unadjusted analyses, blood MeHg, but not THg, decreased significantly between early and late gestation; this decrease was due in part to hemodilution. Percent MeHg (of THg) varied by up to one order of magnitude. Results highlight the importance of Hg speciation in maternal blood samples to assess prenatal MeHg exposure.


Biomarkers/blood , Environmental Exposure/analysis , Mercury/blood , Methylmercury Compounds/blood , Adolescent , Adult , Cohort Studies , Female , Gestational Age , Hospitals, University , Humans , Middle Aged , Mothers , Nutrition Surveys , Pregnancy , Pregnant Women , Seafood , South Carolina , Young Adult
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