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It is known that, as the vast majority of the anthropogenically emitted mercury can be found in aquatic ecosystems, where several methylating bacteria are present, fish consumption represents the most critical intake source of the most toxic form of mercury, the methylmercury (MeHg). The aim of this work is to predict MeHg levels in the fish muscles which, being the edible portion, are part of the human diet. A physiologically based toxicokinetics model was developed to evaluate the kinetics of MeHg in red mullets. Fishes were described by means of a multi-compartment model including stomach, gut, blood, muscles and an additional compartment virtually encompassing all the remaining organs. Absorption, distribution and excretion were modelled considering different MeHg routes of administration and excretion: intake by ingestion of contaminated food, intake and elimination through inhalation-exhalation and excretion through feces. The model has been firstly validated on Terapon jarbua fish (using the weighted least squares method for parameter estimation) to be subsequently readapted to predict methylmercury concentrations in the muscle of red mullets (using an approximate Bayesian computation approach). This simple multicompartmental model could be considered part, a link in the chain, of a wider more complex project aiming at tracking the fate of MeHg from polluted seawater to the human end consumer. The present study could be useful to surveillance organizations in order to carry out a more comprehensive and informed risk assessment analysis and to take appropriate preventive measures by evaluating possible new MeHg concentration thresholds to minimize public health hazards., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A previous study by our group indicated that methylmercury (MeHg) is biotransformed to bismethylmercury sulfide [(MeHg) 2 S)] by interaction with reactive sulfur species (RSS) produced in the body. In the present study, we explored the transformation of MeHg to (MeHg) 2 S in the gut and the subsequent fate of (MeHg) 2 S in vitro and in vivo. An ex vivo experiment suggested the possibility of the extracellular transformation of MeHg to (MeHg) 2 S in the distal colon, and accordingly, the MeHg sulfur adduct was detected in the intestinal contents and feces of mice administered MeHg, suggesting that (MeHg) 2 S is formed through reactions between MeHg and RSS in the gut. In a cell-free system, we found that (MeHg) 2 S undergoes degradation in a time-dependent manner, resulting in the formation of mercury sulfide and dimethylmercury (DMeHg), as determined by X-ray diffraction and gas chromatography/mass spectrometry, respectively. We also identified DMeHg in the expiration after the intraperitoneal administration of (MeHg) 2 S to mice. Thus, our present study identified a new fate of MeHg through (MeHg) 2 S as an intermediate, which leads to conversion of volatile DMeHg in the body., (© 2021. The Author(s).)

We compared the toxicokinetics of methylmercury (MeHg) in KK-Ay type 2 diabetic mice and C57BL/6J mice to evaluate how metabolic changes associated with diabetes affect MeHg toxicokinetics. A single dose of MeHg (0.2, 1, or 5 mg mercury/kg) was administered orally to 12-week-old KK-Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain, kidneys, liver, and pancreas) were measured after 4, 7, 11, and 14 days. The volume of distribution/bioavailability and the elimination rate constant per day were higher in KK-Ay mice, while the terminal elimination half-life was lower in almost all samples of KK-Ay mice. The area under the curve was lower in all blood and almost all tissue samples from KK-Ay mice. Total clearance/bioavailability was lower in all blood and tissue samples of KK-Ay mice at all MeHg doses. These results indicate that MeHg is more rapidly absorbed by, and eliminated from, the blood cells, brain, liver, kidney, and pancreas of KK-Ay mice under the experimental conditions. Different patterns of tissue-to-plasma and tissue-to-whole blood partition coefficients suggest that notable differences in MeHg transfer between plasma and blood cells affect its distribution in tissues of the two mouse strains. These findings are useful to understand the selective distribution of MeHg to target organs and the sensitivity to MeHg in pathological states., (© 2020 John Wiley & Sons, Ltd.)

Methylmercury (MeHg) toxicity is a major environmental concern. In the aquatic reservoir, MeHg bioaccumulates along the food chain until it is consumed by riverine populations. There has been much interest in the neurotoxicity of MeHg due to recent environmental disasters. Studies have also addressed the implications of long-term MeHg exposure for humans. The central nervous system is particularly susceptible to the deleterious effects of MeHg, as evidenced by clinical symptoms and histopathological changes in poisoned humans. In vitro and in vivo studies have been crucial in deciphering the molecular mechanisms underlying MeHg-induced neurotoxicity. A collection of cellular and molecular alterations including cytokine release, oxidative stress, mitochondrial dysfunction, Ca 2+ and glutamate dyshomeostasis, and cell death mechanisms are important consequences of brain cells exposure to MeHg. The purpose of this review is to organize an overview of the mercury cycle and MeHg poisoning events and to summarize data from cellular, animal, and human studies focusing on MeHg effects in neurons and glial cells. This review proposes an up-to-date compendium that will serve as a starting point for further studies and a consultation reference of published studies.

Several studies have demonstrated that heavy metals disrupt energy homeostasis. Leptin inhibits food intake and decreases body weight through activation of its receptor in the hypothalamus. The impact of heavy metals on leptin signaling in the hypothalamus is unclear. Here, we show that the environmental pollutant, methylmercury (MeHg), favors an anorexigenic profile in wild-type males. C57BL/6J mice were exposed to MeHg via drinking water (5 ppm) up to 30 days. Our data shows that MeHg exposure was associated with changes in leptin induced activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in the hypothalamus. In males, the activation of JAK2/STAT3 signaling pathway was sustained by an increase in SOCS3 protein levels. In females, MeHg-activated STAT3 was inhibited by a concomitant increase in PTP1B. Taken together, our data suggest that MeHg enhanced leptin effects in males, favoring an anorexigenic profile in males, which notably, have been shown to be more sensitive to the neurological effects of this organometal than females. A better understanding of MeHg-induced molecular mechanism alterations in the hypothalamus advances the understanding of its neurotoxicity and provides molecular sites for novel therapies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.

Laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) is capable of metal imaging by acquiring local spatial information. However, the preparation of an appropriate standard for quantitative analysis is difficult because the matrices between the standard and the sample should match, and homogeneity of metal concentration in the standard is required. Hence, the aim of this study was to establish a highly quantitative mercury imaging method that utilizes LA-ICP-MS and an appropriate mercury standard consisting of rat tissue. Our standard showed homogeneous mercury concentration and good linearity between concentration and signal intensity, and met the qualifications for quantitative imaging by LA-ICP-MS. Mercury concentration in MeHg-exposed rat kidneys obtained by LA-ICP-MS measurement of the standard (7.84 ± 0.57 µg/g) was comparable to that obtained by cold vapor atomic absorption spectrophotometry (AAS, 7.27 ± 0.46 µg/g). The results indicate that LA-ICP-MS enabled quantitative imaging with the appropriate standard.

Methylmercury (MeHg) is a neurotoxic pollutant widely present in the environment. Initial symptoms of MeHg may include loss of body weight. However, the mechanisms by which MeHg induces body weight changes have yet to be fully elucidated. Body weight is regulated by multiple mechanisms. Whereas multiple peripheral peptides lead to food intake cessation, ghrelin is the only recognized peripheral hormone that stimulates food intake. It exerts its action on Neuropeptide Y/Agouti-related peptide neurons in the hypothalamus. To test if MeHg affects ghrelin signaling C57BL/6J mice (males and females) were exposed to 5 ppm MeHg via drinking water during a month. On days 15 and 30 of MeHg exposure ghrelin was administered intraperitoneally and changes in body weight and food intake were recorded. In addition, changes in ghrelin-induced signaling pathways in hypothalamus were also analyzed. Here, we show that in males, MeHg enhanced ghrelin-induced body weight gain by activating the AMP-activated Kinase (AMPK)/Uncoupled protein 2 (UCP2) signaling pathway. In contrast, in females, MeHg inhibited ghrelin-induced mTOR signaling activation and decreased Npy mRNA expression, thus mitigating the ghrelin-induced weight gain. Combined, our novel results demonstrate, for the first time, that MeHg disrupts the physiological functions of ghrelin differently in males and females., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cardiovascular disease (CVD) is the major cause of morbidity, mortality, and health care costs in the United States, and possibly around the world. Among the various risk factors of CVD, environmental and dietary exposures to mercury (Hg), a highly toxic metal traditionally regarded as a neurotoxin, has been recently suggested as a potential contributor towards human atherosclerotic development. In this study, we investigated the toxicity, type of cell death, dose-dependent uptake, and efflux of inorganic HgII (as HgCl 2 ) and methylmercury or MeHg (as CH 3 HgCl) in EA.hy926 endothelial cells, as these two forms of Hg are often reported to be present in human blood among the general populations (~20-30% as HgII and ~70-80% as MeHg). Our results showed that HgII is more toxic than MeHg to the endothelial cells, owing to the higher uptake into the cytoplasm and perhaps importantly lower efflux of HgII by the cells, thus the "net" accumulation by the endothelial cells is higher for HgII than MeHg when exposed to the same Hg levels in the media. Furthermore, both HgII and MeHg were found to induce apoptotic and necrotic cell death. This study has important implications for the contributions of these two common Hg species to the development of atherosclerosis, an important process leading to CVD.

Chronic kidney disease (CKD) affects over 15 % of the adults in the United States. Pregnant women with CKD present an additional challenge in that they are at increased risk for adverse events such as preterm birth. Exposure to environmental toxicants, such as methylmercury, may exacerbate maternal disease and increase the risk of adverse fetal outcomes. We hypothesized that fetuses of mothers with CKD are more susceptible to accumulation of methylmercury than fetuses of healthy mothers. The current data show that when mothers are in a state of renal insufficiency, uptake of mercury in fetal kidneys is enhanced significantly. Accumulation of Hg in fetal kidneys may be related to the flow of amniotic fluid, maternal handling of Hg, and/or underdeveloped mechanisms for cellular export and urinary excretion. The results of this study indicate that renal insufficiency in mothers leads to significant alterations in the way toxicants such as mercury are handled by maternal and fetal organs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Few published studies have examined whether the elevated concentrations of the nonessential toxic metal mercury (Hg) often observed in shark muscle also occur in the shark brain or whether Hg accumulation affects shark neurophysiology. Therefore, this study examined accumulation and distribution of Hg in the shark brain, as well as effects of Hg on oxidative stress in the shark central nervous system, with particular focus on the Atlantic sharpnose shark (Rhizoprionodon terraenovae). Sharks were collected along the southeastern U.S. coast throughout most of this species' U.S. geographical range. Total Hg (THg) concentrations were measured in and compared between shark muscle and brain, whereas known biomarkers of Hg-induced neurological effects, including glutathione depletion, lipid peroxidation, and concentrations of a protein marker of glial cell damage (S100b), were measured in shark cerebrospinal fluid. Brain THg concentrations were correlated with muscle THg levels but were significantly lower and did not exceed most published thresholds for neurological effects, suggesting limited potential for detrimental responses. Biomarker concentrations supported this premise, because these data were not correlated with brain THg levels. Hg speciation also was examined. Unlike muscle, methylmercury (MeHg) did not comprise a high percentage of THg in the brain, suggesting that differential uptake or loss of organic and inorganic Hg and/or demethylation of MeHg may occur in this organ. Although Hg accumulation in the shark brain generally fell below toxicity thresholds, higher THg levels were measured in the shark forebrain compared with the midbrain and hindbrain. Therefore, there is potential for selective effects on certain aspects of shark neurophysiology if brain Hg accumulation is increased.

Large-bodied predatory sportfish from Missouri reservoirs can contain elevated methylmercury concentrations that are of concern to the health of consumers. The concentration of total mercury (tHg) in the muscle (which > 95% is in the methylated-Hg form) of harvestable-sized largemouth bass (Micropterus salmoides; LMB) was examined to determine which factors contributed to the variability of tHg concentration in sportfish populations among Missouri reservoirs. Mean tHg concentrations in LMB from each reservoir were compared to physical and chemical characteristics of the reservoir and to biological attributes of each LMB population. Low concentrations of tHg (70-170 ng/g wet weight) in LMB from large reservoirs (surface area ≥ 35,680 acres) were likely related to the dilution of chemical Hg forms with water volume and depth. The highest tHg concentrations in LMB (268-542 ng/g) were from reservoirs with low particulate inorganic material (< 1.5 mg/L) and chlorophyll a concentrations (< 14.6 μg/L), and from LMB populations with a low proportion of large fish (proportional size distribution of LMB > 12 inches was < 33%). These relationships suggest that resource competition among LMB likely contributed to tHg bioaccumulation in reservoirs < 930 acres. Small reservoirs located in northern Missouri also may have greater methylation potential due to warmer water temperatures and anoxic conditions, but more data are needed to confirm these interactions. Fish consumption advisories for reservoirs with large surface area and volume could be reduced from one fish meal per month to one per week. To improve Missouri fisheries and protect consumers, management strategies to limit methylation and improve fish growth should be considered to reduce methylmercury bioaccumulation in small- and medium-sized reservoirs.

Despite the bioaccessibility of nutrients and contaminants present in individual seafood products has been thoroughly studied, information is extremely limited in what concerns complete seafood-based meals, where interactions between ingredients may occur. Hence, this study aimed to evaluate the effect of different ingredients and cooking processes in mercury (Hg) and cadmium (Cd) bioaccessibility in complete meals of tuna (Thunnus spp.) and edible crab (Cancer pagurus), respectively. The addition of ingredients/side dishes decreased Hg levels in cooked tuna meals, but increased Hg bioaccessibility (up to 31% of bioaccessible Hg in complete meals, against 13.5% in stewed tuna alone). Cd levels in edible crab meals were significantly decreased by the addition of ingredients (~36% and ~65% decrease in boiled crab and paté, respectively), but its' bioaccessibility was not significantly affected (>94% in all cases). Results showed that the weekly consumption of 2 complete tuna meals does not exceed MeHg tolerable weekly intake (TWI), whereas Cd's TWI is largely surpassed with the consumption of 50 g/week of edible crab meals. This highlights the importance of determining contaminant levels and bioaccessibility in a whole seafood-based meal context, as such approach enables a more realistic assessment of the risks that seafood can pose to consumers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Methylmercury (MeHg) is a toxic chemical compound naturally produced mainly in the aquatic environment through the methylation of inorganic mercury catalyzed by aquatic microorganisms. MeHg is biomagnified in the aquatic food chain and, consequently, piscivorous fish at the top of the food chain possess huge amounts of MeHg (at the ppm level). Some populations that have fish as main protein's source can be exposed to exceedingly high levels of MeHg and develop signs of toxicity. MeHg is toxic to several organs, but the central nervous system (CNS) represents a preferential target, especially during development (prenatal and early postnatal periods). Though the biochemical events involved in MeHg-(neuro)toxicity are not yet entirely comprehended, a vast literature indicates that its pro-oxidative properties explain, at least partially, several of its neurotoxic effects. As result of its electrophilicity, MeHg interacts with (and oxidize) nucleophilic groups, such as thiols and selenols, present in proteins or low-molecular weight molecules. It is noteworthy that such interactions modify the redox state of these groups and, therefore, lead to oxidative stress and impaired function of several molecules, culminating in neurotoxicity. Among these molecules, glutathione (GSH; a major thiol antioxidant) and thiol- or selenol-containing enzymes belonging to the GSH antioxidant system represent key molecular targets involved in MeHg-neurotoxicity. In this review, we firstly present a general overview concerning the neurotoxicity of MeHg. Then, we present fundamental aspects of the GSH-antioxidant system, as well as the effects of MeHg on this system., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Methylmercury (MeHg) is a ubiquitous environmental pollutant, with the nervous system as its main target; however, the neurotoxic mechanisms of MeHg have not been fully elucidated, and no effective therapeutic and preventive drugs are available to mitigate its toxicity. Recent evidence suggests a reduction in the toxicity of MeHg by natural plant extracts., Scope of Review: The aim of this review is to provide an overview of effective natural plant extracts and their putative biochemical mechanisms for blocking gut absorption, enhancing excretion and minimizing toxic effects of MeHg., Major Conclusions: Natural plant extracts may act as potential therapeutics in response to MeHg exposure. The roles plant components play in the reduction of MeHg toxicity may be multifaceted including: (1) attenuating neurobehavioral deficits; (2) facilitating demethylation of MeHg to inorganic mercury; (3) reducing MeHg absorption from the gastrointestinal tract; (4) redistributing MeHg to less sensitive target organs and tissues; (5) promoting enterohepatic circulation of MeHg to increase its biliary and intestinal excretion; (6) restoring intracellular redox status., General Significance: The possible protective effects of natural plant components contribute to the understanding of mechanisms of MeHg toxicity and to the development of novel therapeutic strategies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Methylmercury is a neurotoxicant that is found in fish and rice. MeHg's toxicity is mediated by blockage of -SH and -SeH groups of proteins. However, the identification of MeHg's targets is elusive. Here we focus on the chemistry of MeHg in the abiotic and biotic environment. The toxicological chemistry of MeHg is complex in metazoans, but at the atomic level it can be explained by exchange reactions of MeHg bound to -S(e)H with another free -S(e)H group (R 1 S(e)-HgMe + R 2 -S(e)H ↔ R 1 S(e)H + R 2 -S(e)-HgMe). This reaction was first studied by professor Rabenstein and here it is referred as the "Rabenstein's Reaction". The absorption, distribution, and excretion of MeHg in the environment and in the body of animals will be dictated by Rabenstein's reactions. The affinity of MeHg by thiol and selenol groups and the exchange of MeHg by Rabenstein's Reaction (which is a diffusion controlled reaction) dictates MeHg's neurotoxicity. However, it is important to emphasize that the MeHg exchange reaction velocity with different types of thiol- and selenol-containing proteins will also depend on protein-specific structural and thermodynamical factors. New experimental approaches and detailed studies about the Rabenstein's reaction between MeHg with low molecular mass thiol (LMM-SH) molecules (cysteine, GSH, acetyl-CoA, lipoate, homocysteine) with abundant high molecular mass thiol (HMM-SH) molecules (albumin, hemoglobin) and HMM-SeH (GPxs, Selenoprotein P, TrxR1-3) are needed. The study of MeHg migration from -S(e)-Hg- bonds to free -S(e)H groups (Rabenstein's Reaction) in pure chemical systems and neural cells (with special emphasis to the LMM-SH and HMM-S(e)H molecules cited above) will be critical to developing realistic constants to be used in silico models that will predict the distribution of MeHg in humans., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Neuronal and sensory toxicity of mercury (Hg) compounds has been largely investigated in humans/mammals with a focus on public health, while research in fish is less prolific and dispersed by different species. Well-established premises for mammals have been governing fish research, but some contradictory findings suggest that knowledge translation between these animal groups needs prudence [e.g. the relative higher neurotoxicity of methylmercury (MeHg) vs. inorganic Hg (iHg)]. Biochemical/physiological differences between the groups (e.g. higher brain regeneration in fish) may determine distinct patterns. This review undertakes the challenge of identifying sensitive cellular targets, Hg-driven biochemical/physiological vulnerabilities in fish, while discriminating specificities for Hg forms., Scope of Review: A functional neuroanatomical perspective was conceived, comprising: (i) Hg occurrence in the aquatic environment; (ii) toxicokinetics on central nervous system (CNS)/sensory organs; (iii) effects on neurotransmission; (iv) biochemical/physiological effects on CNS/sensory organs; (v) morpho-structural changes on CNS/sensory organs; (vi) behavioral effects. The literature was also analyzed to generate a multidimensional conceptualization translated into a Rubik's Cube where key factors/processes were proposed., Major Conclusions: Hg neurosensory toxicity was unequivocally demonstrated. Some correspondence with toxicity mechanisms described for mammals (mainly at biochemical level) was identified. Although the research has been dispersed by numerous fish species, 29 key factors/processes were pinpointed., General Significance: Future trends were identified and translated into 25 factors/processes to be addressed. Unveiling the neurosensory toxicity of Hg in fish has a major motivation of protecting ichtyopopulations and ecosystems, but can also provide fundamental knowledge to the field of human neurodevelopment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Understanding methylmercury (MeHg) toxicity requires a complete understanding of its fundamental toxicokinetic and toxicodynamic characteristics in the human body. The biological half-life (t 1/2 ) of MeHg is a kinetic property that directly influences the body burden of Hg that results from repeated exposures such as can occur with fish and seafood consumption. The t 1/2 of MeHg in humans is approximately 50 days, equivalent to an elimination rate (k el ) of 0.014 day -1 . However, numerous studies report a wide range of half-life values (t 1/2  < 30 to >120 days), demonstrating that significant variation in the biological process of MeHg elimination exists. This variation is a source of considerable uncertainty in deriving a meaningful reference dose for MeHg applicable to all individuals in a population., Scope of Review: First, we summarize fundamentals of MeHg toxicokinetics, emphasizing the central role that biological half-life plays in MeHg dosimetry. We next present important considerations for how kinetic analyses are performed. We provide an example of how MeHg half-life variation directly influences the body burden and, in certain contexts, can result in MeHg levels exceeding the US EPA Reference Dose. We then survey existing studies that report MeHg half-life determinations in people., Major Conclusions: Recent advances in methods of determining MeHg kinetics in people have made individualized assessment of MeHg elimination rates more accurate and readily obtainable., General Significance: Characterization of MeHg half-life, particularly in vulnerable individuals, such as pregnant women and children, will diminish the remaining toxicokinetic uncertainty surrounding MeHg exposures and will better inform the risk assessment process., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Coastal marine atmospheric fog has recently been implicated as a potential source of ocean-derived monomethylmercury (MMHg) to coastal terrestrial ecosystems through the process of sea-to-land advection of foggy air masses followed by wet deposition. This study examined whether pumas (Puma concolor) in coastal central California, USA, and their associated food web, have elevated concentrations of MMHg, which could be indicative of their habitat being in a region that is regularly inundated with marine fog. We found that adult puma fur and fur-normalized whiskers in our marine fog-influenced study region had a mean (±SE) total Hg (THg) (a convenient surrogate for MMHg) concentration of 1544 ± 151 ng g -1 (N = 94), which was three times higher (P < 0.01) than mean THg in comparable samples from inland areas of California (492 ± 119 ng g -1 , N = 18). Pumas in California eat primarily black-tailed and/or mule deer (Odocoileus hemionus), and THg in deer fur from the two regions was also significantly different (coastal 28.1 ± 2.9, N = 55, vs. inland 15.5 ± 1.5 ng g -1 , N = 40). We suggest that atmospheric deposition of MMHg through fog may be contributing to this pattern, as we also observed significantly higher MMHg concentrations in lace lichen (Ramalina menziesii), a deer food and a bioindicator of atmospheric deposition, at sites with the highest fog frequencies. At these ocean-facing sites, deer samples had significantly higher THg concentrations compared to those from more inland bay-facing sites. Our results suggest that fog-borne MMHg, while likely a small fraction of Hg in all atmospheric deposition, may contribute, disproportionately, to the bioaccumulation of Hg to levels that approach toxicological thresholds in at least one apex predator. As global mercury levels increase, coastal food webs may be at risk to the toxicological effects of increased methylmercury burdens.

Mercury (Hg) is readily bioaccumulated in seafood, a common ingredient in indigenous cuisines throughout the world. This study investigates Hg speciation in cooked seafood after gastric and intestinal digestion. The results showed that the removal of Hg by washing was negligible. Additionally, the results of our calculations regarding the mass balance of Hg concentration indicated that cooking reduced Hg mainly by means of volatilization and that Hg 2+ was more readily reduced than MeHg. Moreover, cooking lowered the bioaccessibility of Hg in seafood: the reduced percent of bioaccessible Hg 2+ after cooking ranged from 2 to 35% (on average, 16%). The corresponding numbers were slightly lower compared with those for MeHg (on average, 19%). Furthermore, there might be a chemical transformation of Hg during in vitro gastrointestinal digestion. The results of in vivo tests in laboratory mice suggested that methylation of Hg mainly took place in the gastric tract, whereas demethylation of Hg occurred primarily during intestinal digestion. These findings indicate that the bioaccessibility of Hg 2+ and MeHg was not only related to their initial concentrations in the food samples, but also that further studies on the mechanisms of Hg demethylation and methylation during gastrointestinal digestion are essential for more realistic risk assessments., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Consumption of fish/seafood is clearly linked to higher mercury levels in human tissue samples. However, correlations between methylmercury (MeHg) intakes calculated from dietary surveys and mercury body burdens are usually weak and can vary across populations. Different factors may affect MeHg absorption, distribution, metabolism and excretion, including co-exposures to phytochemicals and antibiotics, which were shown to affect mercury body burdens in rodents. Based on the observation that rat pups developmentally exposed to MeHg and a Rhododendron tomentosum extract (Labrador Tea) presented significantly higher blood mercury levels at weaning compared to pups exposed to MeHg alone, the modulation of MeHg toxicokinetics by Labrador Tea was further investigated in adult rats., Results: Total mercury levels were quantified in the blood, liver, kidney and feces of adult male rats exposed to MeHg (1.2 mg/kg bodyweight/day, for 3 weeks) administered either alone or in combination with Labrador Tea (100 mg/kg bodyweight/day) or with an antibiotics cocktail (to inhibit MeHg demethylation by gut bacteria). While the reduced fecal excretion and higher blood mercury levels expected from antibiotics-treated rats were observed, mercury levels in samples from Labrador Tea-treated rats were not significantly different from those measured in samples from rats exposed to MeHg alone.

Stroke is one of the main causes of human disability worldwide. Ischemic stroke is mostly characterized by metabolic collapse and fast tissue damage, followed by secondary damage in adjacent regions not previously affected. Heavy metals intoxication can be associated with stroke incidence, because of their damaging action in the vascular system. Mercury, in particular, possesses a high tropism by metabolically active regions, such as the brain. In the present study we sought to evaluate whether methylmercury (MeHg) intoxication can aggravate the tissue damage caused by an ischemic stroke induced by microinjections of endothelin-1 (ET-1) into the motor cortex of adult rats. Following MeHg intoxication by gavage (0.04 mg/kg/day) during 60 days, the animals were injected with ET-1 (1 μl, 40 pmol/μl) or vehicle (1 μl). After 7 days, all animals were submitted to behavioral tests and then their brains were processed to biochemical and immunohistochemical analyses. We observed that long-term MeHg intoxication promoted a significant Hg deposits in the motor cortex, with concomitant increase of microglial response, followed by reduction of the neuronal population following ischemia and MeHg intoxication, as well as disturbance in the antioxidant defense mechanisms by misbalance of oxidative biochemistry with increase of both lipid peroxidation and nitrite levels, associated to behavioral deficits. MeHg exposure and cortical ischemia demonstrated that both injuries are able of causing significant neurobehavioural impairments in motor coordination and learning accompanied of an exacerbated microglial activation, oxidative stress and neuronal loss in the motor cortex, indicating that MeHg as a source of metabolic disturbance can act as an important increasing factor of ischemic events in the brain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The capacity of two LAB strains to inhibit inorganic [Hg(II)] and organic (methyl-Hg; MeHg) mercury translocation through monolayers of co-cultures of NCM460 and HT29-MTX colonic cells was evaluated. Lactobacillus casei BL23 and Lactobacillus acidophilus ATCC4356 reduced the permeability of Hg(II) and MeHg from aqueous solutions through NCM460/HT29-MTX monolayers (20-94% reduction). However, assays using the bioaccessible (soluble) Hg fraction obtained by in vitro gastrointestinal digestion of Hg-contaminated swordfish only showed a reduction (42%) with the BL23 strain. In vivo experiments carried out in mice receiving an acute dose of Hg(II) or MeHg (0.5 mg/kg body weight/day) with or without lactobacilli resulted in significant decreases of the bioavailability of MeHg with both strains and increased excretion of Hg in feces after treatment with the lactobacilli. However, Hg(II) bioavailability or excretion was not affected. Hg accumulation in liver and kidney remained similar in LAB-treated or non-treated animals. This is the first study of the impact of LAB on Hg(II) and MeHg toxicokinetics and shows that some LAB strains have potential to diminish MeHg bioavailability. Furthermore, it has established the basis for new studies on the protective effect of LAB under conditions resembling subchronic and chronic Hg exposures., (Copyright © 2019. Published by Elsevier Ltd.)

The bioaccumulation and the main source of total Hg (THg) and methylmercury (MMHg) in the deposit-feeding polychaete Neanthes japonica collected in Jinzhou Bay, China, were investigated. Compared with the historical data, THg bioaccumulation in polychaetes collected in sediment of Jinzhou Bay was distinctly higher due to higher sediment THg concentration, but MMHg bioaccumulation was significantly lower. THg accumulation in polychaetes mainly derived from its accumulation in sediment. However, MMHg bioaccumulation in polychaetes did not correlate with Hg concentration in sediment. Besides sediment ingestion, MMHg accumulation in polychaetes may partially source from the process of in vivo transformation. The in vivo Hg methylation may take place in polychaetes, according to the excellent correlation between MMHg concentration and THg and inorganic Hg concentration in polychaetes. The biochemical characters in polychaete body, the oxidation-reduction environment and the microbial activity in polychaete gut may be beneficial to in vivo Hg methylation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The distributions of primary amino acids, MeHg and IHg in body tissues of two commonly farm-raised fish species (common carp: Cyprinus carpio; grass carp: Ctenopharyngodon idellus) in Guizhou Province, SW China, were investigated to understand the effects of primary amino acids on MeHg and IHg metabolism in farm-raised fish. The primary amino acids were classified into four groups: (1) essential and polar amino acids; (2) essential and non-polar amino acids; (3) non-essential and polar amino acids; and (4) non-essential and non-polar amino acids. For both fish species, groups (1, 2 and 3) were enriched in muscle and kidney, whereas group (4) was enriched in scale. The two fish species showed low MeHg concentrations (grass carp: 0.5-3.9 ng/g; common carp:1.0-7.4 ng/g) and low MeHg proportions (grass carp: 2-45%; common carp: 6-37%) in their tissues, which are mainly due to the simple food web structures and the fast growth of the farm-raised fish. Positive correlations (r = 0.342 to 0.472; p < 0.01; n = 78) were observed between MeHg and several primary amino acids (cysteine, threonine, phenylalanine, leucine, valine, glutamate serine and tyrosine) in fish tissues, which may be driven by the formation of MeHg-Cys complexes within fish body. However, no significant correlations were observed between IHg and any primary amino acids, indicating the metabolic processes of IHg and MeHg are different. This study advances our understanding that cysteine and its related/derived amino acids may be an important driving force for MeHg distribution and translocation in fish., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Seafood consumption is widely considered as the primary route for human exposure to the neurotoxin methylmercury (MeHg) that is produced by certain anaerobic microorganisms and can bioaccumulate to high concentration levels in natural aquatic food webs. In this study, a novel methylmercury-binding peptide with seven amino acids was displayed on the cell surfaces of Escherichia coli strain W-1, which was isolated from fish feces and fused with ice nucleation protein. These cells exhibited high affinity and selectivity toward methylmercury. They efficiently removed more than 96% of 12 μM methylmercury, and accumulation of methylmercury in the engineered strain was four times higher than that in the wild type. Transmission electron microscopy confirmed methylmercury accumulation on cell membranes. Carassius auratus was fed by engineered bacteria, which showed a decrease in methylmercury concentration in muscles of about 36.3 ± 0.7%; whereas an increase in methylmercury concentration was observed in the feces (36.7 ± 0.8%) in comparison to the control group. The engineered strain in the gut captured methylmercury and prevented it's absorption by muscles, while some bacteria with methylmercury were excreted in the feces. The surface-engineered E. coli effectively protected fish from methylmercury contamination., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Methylmercury (MeHg) can accumulate in rice and this has been demonstrated to be an important human MeHg exposure pathway. How to reduce MeHg concentrations in rice grains has therefore become a very important public health issue. Previous studies have investigated the role of plant biochars on Hg bioavailability in soils but knowledge of the influence of sewage sludge biochars (SSB) on MeHg formation and bioaccumulation in different soils is lacking. In the present study, SSB was applied to two Hg-contaminated soils, one acid and the other calcareous, in an attempt to stabilize MeHg in the soil and further mitigate MeHg accumulation in rice grains. The results indicate that the presence of SSB may promote Hg methylation in an acid soil. Moreover, MeHg concentrations increased gradually during rice growth, perhaps due to the release of root exudates. SSB can inhibit both MeHg and total Hg (THg) accumulation in different rice tissues. Both MeHg and THg decreased in the rice grains by up to 73.4 and 81.9%, respectively. However, the inhibitory effect was less pronounced in a calcareous soil. This study further demonstrates that biochar application can inhibit MeHg accumulation in soils despite the promotion of MeHg formation in soil by SSB application. However, an effect of biochar on MeHg accumulation was observed only in the acid soil. These results are useful in managing applications of biochars to Hg-contaminated paddy fields., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Humans are exposed simultaneously to a variety of neurotoxic agents, including manganese (Mn) and methylmercury (MeHg). Therefore, the study of combined exposures to toxicants is timely. This work aimed to study changes in cholinergic system focusing on acetylcholinesterase (ace-2), monoaminergic system focusing on vesicular monoamine transporter (VMAT, cat-1) expression, to address changes in antioxidant enzymatic systems, namely, the expression of superoxide dismutase (sod-3 and sod-4) and catalase (ctl-3), as well as worm reproduction and locomotion. C. elegans in the L1 larval stage were exposed to Mn, MeHg or both. All analyses were done 24 h after the end of exposure, except for behavior and reproduction tests that were assessed in L4 larval stage worms. The values obtained for lethal dose 50% (LD 50 ) were 17.78 mM for Mn and 30.63 μM for MeHg. It was observed that body bends, pharyngeal pumping and brood size decreased in worms exposed to metals when undergoing combined exposures. Relative mRNA content of ace-2, cat-1, sod-3, sod-4 and ctl-3 was increased at the highest concentration of the interaction (50 mM Mn + 50 μM MeHg). Cholinergic degeneration was observed in all groups co-exposed to both metals. Notably, combined exposure to metals was more toxic to the worms than when exposed to a single metal., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Newly constructed reservoirs were recognized as hotspot of mercury (Hg) methylation, and then methylmercury (MeHg) accumulation in food chains. The risk of elevated MeHg concentrations in fish is one of the most important concerns in newly constructed reservoirs. The Three Gorges Reservoir (TGR) is one of the largest reservoirs in the world. However, the distribution and bioaccumulation characteristics of Hg species within the food chains and its potential ecological risk in the TGR remain poorly understood. In this study, 264 fish individuals covering 18 species were collected from the TGR. Total mercury (THg) and MeHg concentrations in different organs (gill, heart, liver, muscle and swim bladder) of fish species were analyzed; the values of δ 13 C and δ 15 N in fish muscle were determined as well to reveal the biomagnification properties of Hg in food chains. Our results showed that concentrations of THg (0.5-272 ng g -1 , w.w.) and MeHg (0.1-199 ng g -1 , w.w.) in fish muscle from the TGR ubiquitously fall below the safe fish consumption limit on Hg recommended by WHO (500 ng g -1 , w.w.) and the US-EPA Water Quality Criterion for MeHg (300 ng g -1 , w.w.). The short food web jointly with the limited trophic magnification factor in the TGR explained the relatively low Hg concentrations in predators. Among the five fish organs, muscle represented the highest Hg concentrations, followed by heart, liver, swim bladder, and gill, suggesting that muscle has the highest ability to accumulate Hg compared to the other organs. More importantly, no discernible "reservoir effect" was observed in the TGR within the initial few years after impoundment due to its special eco-environment including: 1) neutral and slightly alkaline pH and low dissolved organic carbon of water, 2) less vegetation coverage in inundated areas, 3) simple food web., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Methylmercury (MeHg) taken up through fish consumption can be transferred from the mother to the fetus during pregnancy. In the present study, pregnant rat mothers were contaminated with environmentally relevant doses of 36 and 76 ng MeHg/g of food using diets containing naturally mercury-containing fish. Young female rats fed with fish-containing food after weaning showed decreased locomotion in Y maze for accumulated concentrations in brain as low as 75 ng Hg/g dry weight (15 ng Hg/g wet weight). Young female rats fed the control diet after weaning yet borne by mothers fed the diet containing 76 ng MeHg/g, presented a 58% reduced activity in the open-field labyrinth, meaning that the maternal exposure to fish-containing food exerted an effect in utero that lasted several weeks after birth. Newborns were protected against Hg exposure by the placental barrier since in newborns from mothers fed the diet containing 76 ng MeHg/g of food, the concentrations of Hg in brain, kidney, liver and skeletal muscles represented 12, 3, 21 and 18% of those of their mother's tissues, respectively. These results suggest the existence, at least in rats, of a threshold level in terms of MeHg exposure above which the placental barrier collapses., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The aim of this study was to determine the distribution of total mercury (THg), methylmercury (CH 3 Hg + ), and inorganic mercury (Hg inorg ) in the tissues and organs of fish depending on species, tissue, and organ, and their bioaccumulation in tissues and biomagnification throughout the trophic web. The study included four species of fish (herring, sprat, cod, and eel) from the southern Baltic Sea. The concentrations of the different forms of mercury were determined in tissues and internal organs. Intra-specific differences in levels of THg, CH 3 Hg + , and Hg inorg in the tissues and organs were determined. Muscle contained the highest proportions of THg and CH 3 Hg + in comparison to that in the internal organs. Differences in concentrations of THg, CH 3 Hg + , and Hg inorg in the tissues and organs of fish were related to their preferred prey. The bioaccumulation of CH 3 Hg+ in the tissues and organs of predatory fish at the highest trophic levels was greater than in the liver and digestive tract of fish species at lower trophic levels, in which Hg inorg predominated. The high concentrations of CH 3 Hg + in eel and cod and the low levels in herring and sprat were linked with their food and the transfer of this element among species. The results suggested that the type of food, feeding habits, and trophic position were important parameters that influenced the transfer and biomagnification of mercury in fish.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We present an alternative approach for establishing in situ bioaccumulation assessment of methyl-Hg (MeHg), total-Hg, Cd, Pb and Zn in bivalve Anomalocardia brasiliana from four bays of Rio de Janeiro presenting varying degrees of eutrophication, acid volatile sulfides (2-55 μmol g -1 ), simultaneously extracted metals (SEM) and total metals (TM) in sediments. Using metal concentrations of composite samples from three size classes of bivalve and their incorporation rates (IR = metal concentration / total length), which depend on exposure time, we calculated asymptotic IR and respective consequent metal concentrations. Both IR and the metal concentration presented inverse relationships with total length (excepting MeHg) and bay contamination. Lead and zinc concentrations were above Brazilian legal criteria in the most anoxic and contaminated bay, suggesting significant metal bioavailability (SEM/TM between 8% and 63%)., (Copyright © 2018. Published by Elsevier Ltd.)

Methylmercury can readily cross the human placental barrier and the blood-brain barrier and cause damage to the vulnerable developing brains of the fetus and infants. Most of the previous studies on the maternal transfer of methylmercury to the next generation have focused on the prenatal period. In this study, human physiologically based pharmacokinetic (PBPK) models of methylmercury were established for breastfeeding mothers and suckling infants based on the existing model prototypes of previous studies. Relevant parameters of the models were modified, and the validation was conducted based on measured data in North China. The models could effectively describe the human lactational transfer of methylmercury, including the time-dependent methylmercury levels in different tissues and organs of the breastfeeding mothers and suckling infants. The results indicated that 77.2% and 14.9% of methylmercury were excreted via hair and breast milk, respectively, from breastfeeding mothers during the first year after delivery. Meanwhile, 79.2% was excreted from the suckling infants during the first year after delivery via hair. Lactational transfer of methylmercury was considered an important pathway of methylmercury exposure for the breastfeeding infants, which accounted for approximately 80% of the accumulated adverse impacts at the early stages of human development., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Mercury in foods, in inorganic form [Hg(II)] or as methylmercury (CH 3 Hg), can have adverse effects. Its elimination from foods is not technologically viable. To reduce human exposure, possible alternatives might be based on reducing its intestinal absorption. This study evaluates the ability of 23 dietary components to reduce the amount of mercury that is absorbed and reaches the bloodstream (bioavailability). We determined their effect on uptake of mercury in Caco-2 cells, a model of intestinal epithelium, exposed to Hg(II) and CH 3 Hg standards and to swordfish bioaccessible fractions. Cysteine, homocysteine, glutathione, quercetin, albumin and tannic reduce bioavailability of both mercury species. Fe(II), lipoic acid, pectin, epigallocatechin and thiamine are also effective for Hg(II). Some of these strategies also reduce Hg bioavailability in swordfish (glutathione, cysteine, homocysteine). Moreover, extracts and supplements rich in these compounds are also effective. This knowledge may help to define dietary strategies to reduce in vivo mercury bioavailability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to estimate the disease burden of methylmercury for children born in Germany in the year 2014. Humans are mainly exposed to methylmercury when they eat fish or seafood. Prenatal methylmercury exposure is associated with IQ loss. To quantify this disease burden, we used Monte Carlo simulation to estimate the incidence of mild and severe mental retardation in children born to mothers who consume fish based on empirical data. Subsequently, we calculated the disease burden with the disability-adjusted life years (DALY)-method. DALYs combine mortality and morbidity in one measure and quantify the gap between an ideal situation, where the entire population experiences the standard life expectancy without disease and disability, and the actual situation. Thus, one DALY corresponds to the loss of one year of life in good health. The methylmercury-induced burden of disease for the German birth cohort 2014 was an average of 14,186 DALY (95% CI 12,915-15,440 DALY). A large majority of the DALYs was attributed to morbidity as compared to mortality. Of the total disease burden, 98% were attributed to mild mental retardation, which only leads to morbidity. The remaining disease burden was a result of severe mental retardation with equal proportions of premature death and morbidity.

Cellular uptake and export are important steps in the biotransformation of mercury (Hg) by microorganisms. However, the mechanisms of transport across biological membranes remain unclear. Membrane-bound transporters are known to be relevant, but passive permeation may also be involved. Inorganic Hg II and methylmercury ([CH 3 Hg II ] + ) are commonly complexed with thiolate ligands. Here, we have performed extensive molecular dynamics simulations of the passive permeation of Hg II and [CH 3 Hg II ] + complexes with thiolate ligands through a model bacterial cytoplasmic membrane. We find that the differences in free energy between the individual complexes in bulk water and at their most favorable position within the membrane are ∼2 kcal mol -1 . We provide a detailed description of the molecular interactions that drive the membrane crossing process. Favorable interactions with carbonyl and tail groups of phospholipids stabilize Hg-containing solutes in the tail-head interface region of the membrane. The calculated permeability coefficients for the neutral compounds CH 3 S-Hg II -SCH 3 and CH 3 Hg II -SCH 3 are on the order of 10 -5 cm s -1 . We conclude that small, nonionized Hg-containing species can permeate readily through cytoplasmic membranes.

Sulfur (S) is an essential element for plant growth and its biogeochemical cycling is strongly linked to the species of heavy metals in soil. In this work, the effects of S (sulfate and elemental sulfur) treatment on the accumulation, distribution and chemical forms of Hg in rice growing in Hg contaminated soil were investigated. It was found that S could promote the formation of iron plaque on the root surface and decrease total mercury (T-Hg) and methylmercury (MeHg) accumulation in rice grains, straw, and roots. Hg in the root was dominated in the form of RS-Hg-SR. Sulfate treatment increased the percentage of RS-Hg-SR to T-Hg in the rice root and changed the Hg species in soil. The dominant Hg species (70%) in soil was organic substance bound fractions. Sulfur treatment decreased Hg motility in the rhizosphere soils by promoting the conversion of RS-Hg-SR to HgS. This study is significant since it suggests that low dose sulfur treatment in Hg-containing water irrigated soil can decrease both T-Hg and MeHg accumulation in rice via inactivating Hg in the soil and promoting the formation of iron plaque in rice root, which may reduce health risk for people consuming those crops., (Copyright © 2017. Published by Elsevier Ltd.)

The Korean National Environmental Health Survey (KoNEHS 2009-2011) tracks levels of environmental pollutants in biological samples from the adult Korean population (age 19-88). Recent survey results for blood mercury (Hg) suggest some exceedance above existing blood Hg reference levels. Because total blood Hg represents both organic and inorganic forms, and methylmercury (MeHg) has been specifically linked to several adverse health outcomes, a need exists to quantify MeHg intake for this population. Gender, age, and frequency of fish consumption were first identified as important predictors of KoNEHS blood Hg levels using generalized linear models. Stratified distributions of total blood Hg were then used to estimate distributions of blood MeHg using fractions of MeHg to total Hg from the literature. Next, a published physiologically based pharmacokinetic (PBPK) model was used to predict distributions of blood MeHg as a function of MeHg intake; ratios of MeHg intake to model-predicted blood MeHg were then combined with KoNEHS-based blood MeHg values to produce MeHg intake estimates. These intake estimates were ultimately compared with the Reference Dose (RfD) for MeHg (0.1 µg/kg/day) and reported as margin of exposure (MOE) estimates for specific KoNEHS subgroups. The derived MOEs across all subgroups, based on estimated geometric mean intake, ranged from 1.6 to 4.1. These results suggest MeHg exposures approaching the RfD for several subgroups of the Korean population, and not just for specific subgroups (eg, those who eat fish very frequently)., (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Total mercury (THg) and methylmercury (MeHg) were recorded in the commercial demersal fish Lethrinus nebulosus, caught from six locations in Qatar EEZ (Exclusive Economic Zone). Concentrations of THg decreased in the order: liver˃muscle˃gonad. THg concentrations in fish tissue ranged from 0.016ppm in gonad to 0.855ppm (mgkg -1 w/w) in liver tissues, while concentrations in muscle tissue ranged from 0.24 to 0.49ppm (mgkg -1 w/w) among sampling sites. MeHg concentrations were used to validate food web transfer rate calculations. Intake rates were calculated to assess the potential health impact of the fish consumption. There is no major threat to human health from the presence of Hg in L. nebulosus, based upon reasonable consumption patterns, limited to no more than three meals of L. nebulosus per week., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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., (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Methylmercury (CH 3 Hg + ) is an environmental toxicant that may lead to significant pathologies in exposed individuals. The current study assessed the disposition and toxicological effects of 2.5 or 7.5mgkg -1 CH 3 Hg + , conjugated to cysteine (Cys; Cys-S-CH 3 Hg) and administered orally to pregnant and non-pregnant Wistar and TR - rats. Rats were euthanized on gestational day 20 and the content of mercury in each fetus, amniotic sac, and placenta was determined. The brain, liver, and kidneys were removed from each fetus for estimation of mercury content. From the dams, a sample of blood, kidneys, liver, and brain were removed at the time of euthanasia. The findings from this study indicate that pregnancy leads to significant changes in the handling of mercuric ions, particularly in the liver. Furthermore, there are significant differences in the handling of non-nephrotoxic and nephrotoxic doses of Cys-S-CH 3 Hg by maternal and fetal organs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The neurotoxicity of methylmercury (MeHg) is well characterised, and the ameliorating effects of selenium have been described. However, little is known about the molecular mechanisms behind this contaminant-nutrient interaction. We investigated the influence of selenium (as selenomethionine, SeMet) and MeHg on mercury accumulation and protein expression in the brain of adult zebrafish ( Danio rerio ). Fish were fed diets containing elevated levels of MeHg and/or SeMet in a 2 × 2 full factorial design for eight weeks. Mercury concentrations were highest in the brain tissue of MeHg-exposed fish compared to the controls, whereas lower levels of mercury were found in the brain of zebrafish fed both MeHg and SeMet compared with the fish fed MeHg alone. The expression levels of proteins associated with gap junction signalling, oxidative phosphorylation, and mitochondrial dysfunction were significantly ( p < 0.05) altered in the brain of zebrafish after exposure to MeHg and SeMet alone or in combination. Analysis of upstream regulators indicated that these changes were linked to the mammalian target of rapamycin (mTOR) pathways, which were activated by MeHg and inhibited by SeMet, possibly through a reactive oxygen species mediated differential activation of RICTOR, the rapamycin-insensitive binding partner of mTOR.

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na + - K + ATP-ase pump (Cd, MeHg), biological Ca +2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The current study aims to shed light on the neurotoxicity of MeHg in fish (white seabream - Diplodus sargus) by the combined assessment of: (i) MeHg toxicokinetics in the brain, (ii) brain morphometry (volume and number of neurons plus glial cells in specific brain regions) and (iii) fish swimming behavior (endpoints associated with the motor performance and the fear/anxiety-like status). Fish were surveyed for all the components after 7 (E7) and 14 (E14) days of dietary exposure to MeHg (8.7μgg -1 ), as well as after a post-exposure period of 28days (PE28). MeHg was accumulated in the brain of D. sargus after a short time (E7) and reached a maximum at the end of the exposure period (E14), suggesting an efficient transport of this toxicant into fish brain. Divalent inorganic Hg was also detected in fish brain along the experiment (indicating demethylation reactions), although levels were 100-200 times lower than MeHg, which pinpoints the organic counterpart as the great liable for the recorded effects. In this regard, a decreased number of cells in medial pallium and optic tectum, as well as an increased hypothalamic volume, occurred at E7. Such morphometric alterations were followed by an impairment of fish motor condition as evidenced by a decrease in the total swimming time, while the fear/anxiety-like status was not altered. Moreover, at E14 fish swam a greater distance, although no morphometric alterations were found in any of the brain areas, probably due to compensatory mechanisms. Additionally, although MeHg decreased almost two-fold in the brain during post-exposure, the levels were still high and led to a loss of cells in the optic tectum at PE28. This is an interesting result that highlights the optic tectum as particularly vulnerable to MeHg exposure in fish. Despite the morphometric alterations reported in the optic tectum at PE28, no significant changes were found in fish behavior. Globally, the effects of MeHg followed a multiphasic profile, where homeostatic mechanisms prevented circumstantially morphometric alterations in the brain and behavioral shifts. Although it has become clear the complexity of matching brain morphometric changes and behavioral shifts, motor-related alterations induced by MeHg seem to depend on a combination of disruptions in different brain regions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Methylmercury contamination of the environment is an important issue globally, and birds are useful bioindicators for mercury monitoring programs. The available data on mercury contamination of birds in western North America were synthesized. Original data from multiple databases were obtained and a literature review was conducted to obtain additional mercury concentrations. In total, 29219 original bird mercury concentrations from 225 species were compiled, and an additional 1712 mean mercury concentrations, representing 19998 individuals and 176 species, from 200 publications were obtained. To make mercury data comparable across bird tissues, published equations of tissue mercury correlations were used to convert all mercury concentrations into blood-equivalent mercury concentrations. Blood-equivalent mercury concentrations differed among species, foraging guilds, habitat types, locations, and ecoregions. Piscivores and carnivores exhibited the greatest mercury concentrations, whereas herbivores and granivores exhibited the lowest mercury concentrations. Bird mercury concentrations were greatest in ocean and salt marsh habitats and lowest in terrestrial habitats. Bird mercury concentrations were above toxicity benchmarks in many areas throughout western North America, and multiple hotspots were identified. Additionally, published toxicity benchmarks established in multiple tissues were summarized and translated into a common blood-equivalent mercury concentration. Overall, 66% of birds sampled in western North American exceeded a blood-equivalent mercury concentration of 0.2 μg/g wet weight (ww; above background levels), which is the lowest-observed effect level, 28% exceeded 1.0 μg/g ww (moderate risk), 8% exceeded 3.0 μg/g ww (high risk), and 4% exceeded 4.0 μg/g ww (severe risk). Mercury monitoring programs should sample bird tissues, such as adult blood and eggs, that are most-easily translated into tissues with well-developed toxicity benchmarks and that are directly relevant to bird reproduction. Results indicate that mercury contamination of birds is prevalent in many areas throughout western North America, and large-scale ecological attributes are important factors influencing bird mercury concentrations., (Published by Elsevier B.V.)

Methylmercury (MeHg) is a global contaminant of concern and human exposures are largely realized via seafood consumption. While it is assumed that 95-100% of the ingested MeHg from seafood reaches systemic circulation, recent in vitro studies have yielded results to suggest otherwise. Of the published studies to have characterized the bioaccessibility or bioavailability of MeHg from seafood, only a handful of seafood species have been characterized, there exists tremendous variability in data within and across species, few species of relevance to North America have been studied, and none of the in vitro studies have adapted results to an epidemiology study. The objective of the current study was two-fold: (a) to characterize in vitro MeHg bioaccessibility and bioavailability from ten commonly consumed types of seafood in North America; and (b) to apply the bioaccessibility and bioavailability data from the in vitro study to an existing human MeHg exposure assessment study. Raw seafood samples (cod, crab, halibut, salmon, scallop, shrimp, tilapia, and three tuna types: canned light, canned white, fresh) were purchased in Montreal and their MeHg concentrations generally overlapped with values reported elsewhere. The bioaccessibility of MeHg from these samples ranged from 50.1±19.2 (canned white tuna) to 100% (shrimp and scallop) of the amount measured in the raw undigested sample. The bioavailability of MeHg from these samples ranged from 29.3±10.4 (crab) to 67.4±9.7% (salmon) of the value measured in the raw undigested sample. There were significant correlations between the initial MeHg concentration in seafood with the percent of that Hg that was bioaccessible (r=-0.476) and bioavailable (r=-0.294). When the in vitro data were applied to an existing MeHg exposure assessment study, the estimated amount of MeHg absorbed into systemic circulation decreased by 25% and 42% when considering bioaccessibility and bioavailability, respectively. When the in vitro data were integrated into a regression model relating dietary MeHg intake from seafood with hair and blood Hg biomarkers, there were no differences in key model parameters when comparing the default model (that assumes 100% bioavailability) with models adjusted for the in vitro bioaccessibility and bioavailability data. In conclusion this work adds to a growing number of studies that together suggest that MeHg bioavailability from seafood may be less than 100%, but also documents the challenges when integrating such in vitro data into human exposure and risk assessments., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The ability of modified dietary fiber (MDF) generated from cassava pulp to modulate the bioaccessibility and intestinal absorption of heavy metals may be helpful to mitigate health risk associated with select foods including select fish high in methyl mercury. Using a coupled in vitro digestion/Caco-2 human intestinal cell model, the reduction of fish mercury bioaccessibility and intestinal uptake by MDF was investiaged. MDF was prepared from cassava pulp, a byproduct of tapioca production. The highest yield (79.68%) of MDF was obtained by enzymatic digestion with 0.1% α-amylase (w/v), 0.1% amyloglucosidase (v/v) and 1% neutrase (v/v). MDF and fish tissue were subjected to in vitro digestion and results suggest that MDF may reduce mercury bioaccessibility from fish to 34% to 85% compared to control in a dose-dependent manner. Additionally, accumulation of mercury from digesta containing fish and MDF was only modestly impacted by the presence of MDF. In conclusion, MDF prepared from cassava pulp may be useful as an ingredient to reduce mercury bioavailability from food such as fish specifically by inhibiting mercury transfer to the bioaccessibile fraction during digestion., (© 2016 Institute of Food Technologists®)

In the present study, the concentration of trace elements, total mercury (Hg) and selenium (Se) and mercury forms (MeHg, Hginorg and HgSe) in the vulnerable coastal dolphins Pontoporia blainvillei and Sotalia guianensis were appraised and compared, using metallothioneins (MT) and glutathione (GSH) as biomarkers for trace element exposure. The trace element concentrations varied between muscle and liver tissues, with liver of all dolphin specimens showing higher Hg and Se concentrations than those found in muscle. Hg, MeHg and Hginorg molar concentrations showed a clear increase with Se molar concentrations in the liver of both dolphins, and Se concentrations were higher than those of Hg on a molar basis. Se plays a relevant role in the detoxification of MeHg in the hepatic tissue of both dolphins, forming Hg-Se amorphous crystals in liver. In contrast, MT were involved in the detoxification process of Hginorg in liver. GSH levels in P. blainvillei and S. guianensis muscle tissue suggest that these dolphins have different diving capacities. Muscle Hg concentrations were associated to this tripeptide, which protects dolphin cells against Hg stress., (Copyright © 2016 Elsevier Ltd. All rights reserved.)