Factors in Fish Modifying Methylmercury Toxicity and Metabolism

We report here some results of a long-term (19 month) study with cats fed methylmercury (MeHg) in nutritionally balanced diets based on fish. By using either freshwater pike (low in Se) or canned tuna (high in Se) as the major protein source, basal diets with low levels of MeHg were prepared having different Se content, all Se being of natural origin. The basal diets produced no signs of toxicity or pathological changes over the l9-month period. In cats fed basal diets spiked with medium or high levels of MeHg, evidence for delayed onset of toxic effects from the added MeHg was observed with the tuna diets compared to pike diets. In brain, muscle, and blood, the activity of GSH peroxidase, a selenoenzyme, was decreased by Hg. In liver, substantial accumulation of Hg with Se occured (molar Hg/Se ratio approximately 1.4 to 1.8) but GSH peroxidase activity was unaffected. We suggest that the coaccumulation of Hg and Se in liver measures the extent to which MeHg has been metabolically transformed by metabolism to Hg++, and inactivated by deposition as a Hg/Se complex of low bioavailability. The accumulation of Hg and Se in liver was much greater in cats fed tuna compared to pike, out of proportion to the relatively small differences in Hg and Se content of the tuna and pike basal diets. Some mechanisms are described by which selenium, vitamin E, and other factors might facilitate MeHg breakdown to inorganic Hg during long term low level exposure to MeHg.     

Mercury and selenium interaction in vivo: effects on thioredoxin reductase and glutathione peroxidase

Mercury compounds exert toxic effects via interaction with many vital enzymes involved in antioxidant regulation, such as selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (GPx). Selenium supplementation can reactivate the mercury-inhibited TrxR and recover the cell viability in vitro. To gain an insight on how selenium supplementation affects mercury toxicity in vertebrates, we investigated the effects of selenium on the mercury accumulation and TrxR and GPx activities in a fish model. Juvenile zebra-seabreams were exposed either to methylmercury (MeHg) or inorganic mercury (Hg(2+)) in the presence or absence of sodium selenite (Se) for 28 days followed by 14 days of depuration. Mercury accumulation was found to be 10-fold higher under MeHg exposure than under Hg(2+) exposure. Selenium supplementation caused a half decrease of the accumulation of MeHg but did not influence Hg(2+) accumulation. Exposure to both mercurials led to a decrease of the activity of TrxR (<50% of control) in all organs. Se supplementation coincident with Hg(2+) exposure protected the thioredoxin system in fish liver. However, supplementation of Se during the depuration phase had no effects. The activity of GPx was only affected in the brain of fishes upon the exposure to MeHg and coexposure to MeHg and Se. Selenium supplementation has a limited capacity to prevent mercury effects in brain and kidney. These results demonstrate that Se supplementation plays a protective role in a tissue-specific manner and also highlight the importance of TrxR as a main target for mercurials in vivo.     

Mercury–Selenium Species Ratio in Representative Fish Samples and Their Bioaccessibility by an In Vitro Digestion Method

The potential toxicity of mercury (Hg) content in fish has been widely evaluated by the scientific community, with Methylmercury (MeHg) being the only legislated species (1 mg kg⁻¹, maximum concentration allowed in predatory fish). On the other hand, selenium (Se) is recognized to decrease its toxicity when both elements are simultaneously administrated. In the present paper, the total content of Se and Hg and their species in fish of high consumption, such as tuna, swordfish, and sardine, have been evaluated. The percentage of MeHg is higher than 90% of total Hg content. The results show that, for all of them, the Se/Hg ratio is significantly higher than one, being the maximum ratio for sardine. As only studying the bioaccessible fraction the extent of a toxic effect caused by an element can be predicted, the bioaccessibility of both analytes through an in vitro digestion method has been carried out. The results show that MeHg in all fishes is very low bioaccessible in both gastric and intestinal digestion. Because the MeHg bioaccessible fraction might be correlated to the Se content, the potential toxicity cannot be only related to the total Hg content but also to Se/Hg ratio.     

The Nail as a Noninvasive Indicator of Methylmercury Exposures and Mercury/Selenium Molar Ratios in Brain, Kidney, and Livers of Long-Evans Rats

Animal studies indicate that the toxic effects of methylmercury (MeHg) exposures increase when selenium (Se) status is low. Toxicity is directly proportional to Hg/Se molar ratios in critical tissues such as brain and increase dramatically as molar ratios exceed 1:1. In this study, we examined the nail as a biomonitor of Hg/Se molar ratios in kidney, liver, and brain tissues of weanling male Long-Evans rats fed controlled diets containing varying amounts of Se and MeHg. Linear regression analyses indicate that the natural log transform of the Hg/Se ratio in the nails is strongly related to the Hg/Se molar ratio in kidney, liver, and brain (p?相似文献   

Importance of Molar Ratios in Selenium-Dependent Protection Against Methylmercury Toxicity

The influence of dietary selenium (Se) on mercury (Hg) toxicity was studied in weanling male Long Evans rats. Rats were fed AIN-93G-based low-Se torula yeast diets or diets augmented with sodium selenite to attain adequate- or rich-Se levels (0.1, 1.0 or 15 μmol/kg, respectively) These diets were prepared with no added methylmercury (MeHg) or with moderate- or high-MeHg (0.2, 10 or 60 μmol/kg, respectively). Health and weights were monitored weekly. By the end of the 9-week study, MeHg toxicity had impaired growth of rats fed high-MeHg, low-Se diets by approximately 24% (p < 0.05) compared to the controls. Growth of rats fed high-MeHg, adequate-Se diets was impaired by approximately 8% (p < 0.05) relative to their control group, but rats fed high-MeHg, rich-Se diets did not show any growth impairment. Low-MeHg exposure did not affect rat growth at any dietary Se level. Concentrations of Hg in hair and blood reflected dietary MeHg exposure, but Hg toxicity was more directly related to the Hg to Se ratios. Results support the hypothesis that Hg-dependent sequestration of Se is a primary mechanism of Hg toxicity. Therefore, Hg to Se molar ratios provide a more reliable and comprehensive criteria for evaluating risks associated with MeHg exposure.     

Mercury's neurotoxicity is characterized by its disruption of selenium biochemistry

Background

Methylmercury (CH₃Hg⁺) toxicity is characterized by challenging conundrums: 1) “selenium (Se)-protective” effects, 2) undefined biochemical mechanism/s of toxicity, 3) brain-specific oxidative damage, 4) fetal vulnerability, and 5) its latency effect. The “protective effects of Se” against CH₃Hg⁺ toxicity were first recognized >50?years ago, but awareness of Se's vital functions in the brain has transformed understanding of CH₃Hg⁺ biochemical mechanisms. Mercury's affinity for Se is ~1 million times greater than its affinity for sulfur, revealing it as the primary target of CH₃Hg⁺ toxicity.

Quantification and speciation of mercury and selenium in fish samples of high consumption in Spain and Portugal

Mercury (Hg) and selenium (Se) determinations were carried out to evaluate human exposure to those elements through fish consumption in Spain and Portugal. Atomic fluorescence spectroscopy (AFS) was applied in a cold vapor mode for total mercury quantification and was also hyphenated to gas chromatography (GC) to achieve the speciation of organomercurial species in fish samples. The results obtained show the highest concentration of Hg in swordfish and tuna (0.47+/-0.02 and 0.31+/-0.01 microg g-1, respectively), and a much lower concentration in sardine, mackerel shad, and octopus (0.048+/-0.002, 0.033+/-0.001, and 0.024+/-0.001 microg g-1, respectively). The determination of alkyl mercury compounds revealed that 93-98% of mercury in the fish samples was in the organic form. Methylmercury (MeHg) was the only species found in the three fish species with higher mercury content.Total selenium concentration was high in sardine, swordfish, and tuna (0.43+/-0.02, 0.47+/-0.02, and 0.92+/-0.01 microg g-1, respectively), but low in mackerel shad and octopus (0.26+/-0.01 and 0.13+/-0.01 microg g-1, respectively). Speciation of selenium compounds was done by high-performance liquid chromatography in conjunction with inductively coupled plasma mass spectrometry (LC-ICP-MS). Selenomethionine (SeMet) was the only selenium compound identified in the fish samples with higher selenium content.Among the fish species studied, sardine had the most favourable Se:Hg and SeMet:MeHg molar ratios; therefore, its consumption seems to be preferable.     

Selenoprotein W as molecular target of methylmercury in human neuronal cells is down-regulated by GSH depletion

Methylmercury (MeHg) is well known as a neurotoxic chemical. However, little is mentioned about its neurotoxic mechanism or molecular target in human neuronal cells in particular. We show in this study that exposure of human neuronal cell line, SH-SY5Y, to MeHg dose- and time-dependently impairs viability and mRNA expression of selenoprotein W (SeW) with a significant difference, unlike other selenoenzymes such as, SeP, GPX4, 5DI, and 5'DI. Using real-time RT PCR, the influence of selenium (Se) and glutathione (GSH) on SeW expression was also investigated. While Se depletion caused a weakly reduced SeW mRNA levels, additional Se caused an increase of SeW mRNA levels. Although 2 mM GSH had induced a weak shift on SeW level, the expression of SeW mRNA was down-regulated in SH-SY5Y cells treated with 25 microM BSO, an inhibitor of GSH synthesis. To understand the relationship between a decrease of SeW expression and intracellular GSH and ROS, we measured the concentration of intracellular GSH and ROS in cells treated to 1.4 microM MeHg using fluorescence based assays. A positive correlation was found between SeW mRNA level and intracellular GSH but no significant correlation was observed between intracellular ROS and SeW mRNA level or intracellular GSH contents. Therefore, we suggest that SeW is the novel molecular target of MeHg in human neuronal cells and down-regulation of this selenoenzyme by MeHg is dependent not on generation of ROS but on depletion of GSH.     

Bioaccumulation and Trophic Transfer of Mercury and Selenium in African Sub-Tropical Fluvial Reservoirs Food Webs (Burkina Faso)

The bioaccumulation and biomagnification of mercury (Hg) and selenium (Se) were investigated in sub-tropical freshwater food webs from Burkina Faso, West Africa, a region where very few ecosystem studies on contaminants have been performed. During the 2010 rainy season, samples of water, sediment, fish, zooplankton, and mollusks were collected from three water reservoirs and analysed for total Hg (THg), methylmercury (MeHg), and total Se (TSe). Ratios of δ¹³C and δ¹⁵N were measured to determine food web structures and patterns of contaminant accumulation and transfer to fish. Food chain lengths (FCLs) were calculated using mean δ¹⁵N of all primary consumer taxa collected as the site-specific baseline. We report relatively low concentrations of THg and TSe in most fish. We also found in all studied reservoirs short food chain lengths, ranging from 3.3 to 3.7, with most fish relying on a mixture of pelagic and littoral sources for their diet. Mercury was biomagnified in fish food webs with an enrichment factor ranging from 2.9 to 6.5 for THg and from 2.9 to 6.6 for MeHg. However, there was no evidence of selenium biomagnification in these food webs. An inverse relationship was observed between adjusted δ¹⁵N and log-transformed Se:Hg ratios, indicating that Se has a lesser protective effect in top predators, which are also the most contaminated animals with respect to MeHg. Trophic position, carbon source, and fish total length were the factors best explaining Hg concentration in fish. In a broader comparison of our study sites with literature data for other African lakes, the THg biomagnification rate was positively correlated with FCL. We conclude that these reservoir systems from tropical Western Africa have low Hg biomagnification associated with short food chains. This finding may partly explain low concentrations of Hg commonly reported in fish from this area.     

The importance of selenium and the effects of its deficiency in animal health

Selenium (Se) is an essential trace element in animal nutrition, and exerts multiple actions related to animal production, fertility and disease prevention. Glutathione peroxidase (GSH-PX) enzyme was the first proven selenoenzyme that can prevent oxidative damage of the cellular membrane. Actually more than 30 selenoenzymes have been described and a hierarchy process for expression in the animal has been established. White muscle disease (WMD) was the first recognized condition associated with Se deficiency. WMD causes new born mortality, especially in ruminants, and impaired production condition in growing and adult animals. Selenium is critical to thyroid hormone synthesis and it is also very important for converting T4 (thyroxin inactive form) to T3 (active form). A good immune response requires Se too. Selenium status in soil, plants and animal blood and tissue can be used in the diagnosis of Se deficiency. Diverse forms of Se supplements are available, but many factors affect their activity and efficacy, such as its chemical form and animal's health and production condition. The relationships between foetus Se metabolism and pregnant dam Se status are critical for productivity and need further research.     

东太平洋浅海长尾鲨母体和胚胎间痕量元素的迁移规律

大洋中上层鲨鱼多为金枪鱼渔业的兼捕渔获,因其生长缓慢、繁殖力低等生活史特征,极易被过度捕捞,90%种类资源已近危。而作为长生命周期的顶级捕食者,鲨鱼体内某些过高的痕量元素含量不利于资源恢复。本研究选取10尾东太平洋雌性浅海长尾鲨(Alopias pelagicus)及对应的18尾胚胎,测定其肌肉和肝脏中锌(Zn)、铜(Cu)、铬(Cr)、镍(Ni)、锰(Mn)、硒(Se)、钴(Co)、汞(Hg)、镉(Cd)、铅(Pb)和砷(As) 11种痕量元素,探寻浅海长尾鲨繁殖过程中母体与胚胎间痕量元素的迁移规律。结果表明: 对于必需元素,胚胎两种组织的Cr、Cu、Se和Mn含量均高于母体对应组织,而Ni和Zn含量在胚胎肌肉中较高、肝脏中较低;对于非必需元素,胚胎两种组织的As、Cd和Hg含量均低于母体对应组织。虽然Hg在母体和胚胎组织中含量均较高,但胚胎组织的Se/Hg均大于1,且其在胚胎中的值均大于母体,表明Se在胚胎中具有显著抑制Hg毒性的作用。肝脏作为鲨鱼胚胎发育的主要能量来源,其元素含量在胚胎与母体之间无显著相关性。由此推测,浅海长尾鲨可能存在特定的元素调控机制,以维持胚胎组织中元素含量的稳定。     

Evaluation of a Questionnaire-Based Method for the Estimation of Methylmercury Exposure of Recreational Anglers in the James Bay Territory (Québec,Canada)

The impoundment of reservoirs temporarily increases the methylation of mercury bound to flooded soils and vegetation and the transfer of methylmercury (MeHg) to fish. MeHg levels in various fish species of hydroelectric reservoirs located in the James Bay territory increased by factors of 3 to 7, then gradually declined toward initial concentrations 10 to 20 years after flooding, depending on reservoir characteristics. The potential risk of increased MeHg exposure for recreational anglers who consume fish from these reservoirs had not been assessed previously. A less invasive method than systematic measurement of Hg levels in hair was developed to determine MeHg exposure of recreational anglers. A fish consumption questionnaire-based approach was combined with a toxicokinetic model to estimate the corresponding hair MeHg concentrations. The results were compared with actual analytical determinations of hair Hg levels for the 94 recreational anglers recruited for the study. The values predicted by the model based on self-reporting consumption overestimated actual hair Hg levels by an average factor greater than 6. The mean hair level predicted for the most recent period (September-October) was 23.3?µg.g^?1 compared to 3.6 µg.g^?1 for the measured value. Although the questionnaire protocol may certainly be improved to increase the precision of estimations, direct hair Hg measurement remains the more effective means to assess Hg exposure.     

Effect of selenium depletion and supplementation on the kinetics of type 1 5′-iodothyronine deiodinase and T3/T4 in rats

Presently, the effect of selenium (Se) deficiency and excess of Se (1 ppm) on the activity of selenoenzymes type 1 5′-iodothyronine deiodinase (5′-DI), glutathione peroxidase (GSH-Px), and level of thyroid hormones (T₃ and T₄) was studied in rats. Se levels in the serum and liver, T₃ and T₄ in the serum, GSH-Px levels in the liver, and 5′-DI activity in the liver/aorta/thyroid were estimated after 1, 2, and 3 mo of Se-deficient (0.02 ppm), Se-adequate (0.2 ppm), and Se-excess (1 ppm) diet feeding. All of these parameters decreased significantly in the Se-deficient group as compared to the adequate group. Within the deficient group, as the Se deficiency progressed, all of the parameters except 5′-DI decreased after 2 and 3 mo in comparison to 1-mo data. Thyroidal 5′-DI activity in Se deficiency showed the maximum increase. A significant increase was observed in all of the above parameters in the 1 ppm Se-supplemented diet group when compared with the adequate Se group; also, as the Se deposition increased within the Se-excess diet group, a significant increase was observed in all of the above parameters. However, as observed by others, the intake of excess of Se (i.e., 2 ppm in the diet) did not elevate the activities of selenoenzymes and thyroid hormones; rather, it had adverse effects. The present study concludes that Se supplementation at least up to 1 ppm enhances the selenoenzyme activities, and above this level, it may not be considered as an indicator of selenoenzyme activities.     

The Influence of Long-term Mercury Exposure on Selenium Availability in Tissues: An Evaluation of Data

The precise mechanisms of mercury accumulation and retention are still unclear. Generally, the association of mercury with selenium is used to explain these phenomena. It seems that the presence of coaccumulated endogenous Se can protect cells from the harmful effects of Hg. However, as speculated by some authors, this binding of Se to Hg can also result in a relative deficiency of biologically available Se needed for selenoenzyme syntheses. Deriving from the assumption that Hg deposited in tissues is bound to Se in a 1:1 ratio, the quantity of non-Hg bound Se could be calculated by the difference between the molar contents of the two elements (Se_mol–Hg_mol). In this study we applied such an approach to the data from our previous investigation, where Hg and Se concentrations were determined in autopsy samples of mercury exposed retired Idrija mercury mine workers, Idrija residents living in a Hg contaminated environment and a control group with no known Hg exposure from the environment. Based on these data we tried to estimate the influence of Hg exposure on the physiologically available selenium content in selected tissues, particularly endocrine glands and brain tissues. Comparing the calculated values of (Se_mol– Hg_mol) it was found that for Idrija residents the values were similar to those of the control group and as expected, diminished values were found in some mercury-loaded organs of retired Idrija miners. It could be speculated that in Idrija residents Hg sequestration of selenium is sufficiently compensated by increased Se levels, but that particularly in active miners and in some organs of retired miners, the activity and/or synthesis of selenoenzymes could be disturbed. Part of the study was presented at the 7th International Conference on Mercury as a Global Pollutant, June 27–July 2, 2004 Ljubljana, Slovenia (Falnoga et al. 2000)     

Variation in the biological half-life of methylmercury in humans: Methods,measurements and meaning

BackgroundUnderstanding 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 reviewFirst, 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 conclusionsRecent advances in methods of determining MeHg kinetics in people have made individualized assessment of MeHg elimination rates more accurate and readily obtainable.General significanceCharacterization 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.     

Identification and Determination of Selenoneine, 2-Selenyl-N α , N α , N α -Trimethyl-l-Histidine, as the Major Organic Selenium in Blood Cells in a Fish-Eating Population on Remote Japanese Islands

Selenoneine is the major selenium compound in fish muscles, and fish appears to be an important source of selenium in the fish-eating population. Selenoneine has strong antioxidant activity and a detoxifying function against methylmercury (MeHg) toxicity. Dietary intake, bioaccumulation, and metabolism of selenoneine have not been characterized in humans. A nutritional survey was conducted in remote islands of the Kagoshima Prefecture in Japan. To evaluate the potential risks and benefits of fish consumption for health, we measured concentrations of selenoneine, total selenium, MeHg, inorganic mercury, and polyunsaturated fatty acid (LC-PUFA) in the blood of a fish-eating human population. The erythrocyte, leukocyte, and platelet residues following removal of serum (cellular fraction) contained 0.510 μg Se/g, 0.212 μg selenoneine Se/g, and 0.262 μg Se-containing proteins Se/g, whereas the serum contained 0.174 μg total Se/g. Selenoneine was highly concentrated in the cellular fraction in a manner that was dependent on subjects' frequency of fish consumption. Concentrations of selenoneine were closely correlated with concentrations of MeHg in the cellular fraction. Selenoneine is the major chemical form of selenium in the blood cells of this fish-eating human population and may be an important biomarker for selenium redox status.     

Superoxide dismutase and glutathione peroxidase activities in neutrophils from selenium deficient and copper deficient cattle

Oxygen consumption and the activities of the selenoenzyme glutathione peroxidase, and of the hexose monophosphate shunt were lower than normal in neutrophils from Se deficient cattle. However, these activities and the activity of Cu/zinc superoxide dismutase were unaffected in neutrophils from Cu deficient cattle. These results are discussed with reference to impaired neutrophil microbicidal activity previously demonstrated to result from Se or Cu deficiency in cattle.