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      Selenium Health Benefit Values: Updated Criteria for Mercury Risk Assessments

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          Abstract

          Selenium (Se)-dependent enzymes (selenoenzymes) protect brain tissues against oxidative damage and perform other vital functions, but their synthesis requires a steady supply of Se. High methylmercury (CH 3Hg) exposures can severely diminish Se transport across the placenta and irreversibly inhibit fetal brain selenoenzymes. However, supplemental dietary Se preserves their activities and thus prevents pathological consequences. The modified Se health benefit value (HBV Se) is a risk assessment criterion based on the molar concentrations of CH 3Hg and Se present in a fish or seafood. It was developed to reflect the contrasting effects of maternal CH 3Hg and Se intakes on fetal brain selenoenzyme activities. However, the original equation was prone to divide-by-zero-type errors whereby the calculated values increased exponentially in samples with low CH 3Hg contents. The equation was refined to provide an improved index to better reflect the risks of CH 3Hg exposures and the benefits provided by dietary Se. The HBV Se provides a biochemically based perspective that confirms and supports the FDA/EPA advice for pregnant and breast-feeding women regarding seafoods that should be avoided vs. those that are beneficial to consume. Since Se can be highly variable between watersheds, further evaluation of freshwater fish is needed to identify locations where fish with negative HBV Se may arise and be consumed by vulnerable subpopulation groups.

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          Most cited references39

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          Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study.

          Seafood is the predominant source of omega-3 fatty acids, which are essential for optimum neural development. However, in the USA, women are advised to limit their seafood intake during pregnancy to 340 g per week. We used the Avon Longitudinal Study of Parents and Children (ALSPAC) to assess the possible benefits and hazards to a child's development of different levels of maternal seafood intake during pregnancy. 11,875 pregnant women completed a food frequency questionnaire assessing seafood consumption at 32 weeks' gestation. Multivariable logistic regression models including 28 potential confounders assessing social disadvantage, perinatal, and dietary items were used to compare developmental, behavioural, and cognitive outcomes of the children from age 6 months to 8 years in women consuming none, some (1-340 g per week), and >340 g per week. After adjustment, maternal seafood intake during pregnancy of less than 340 g per week was associated with increased risk of their children being in the lowest quartile for verbal intelligence quotient (IQ) (no seafood consumption, odds ratio [OR] 1.48, 95% CI 1.16-1.90; some, 1.09, 0.92-1.29; overall trend, p=0.004), compared with mothers who consumed more than 340 g per week. Low maternal seafood intake was also associated with increased risk of suboptimum outcomes for prosocial behaviour, fine motor, communication, and social development scores. For each outcome measure, the lower the intake of seafood during pregnancy, the higher the risk of suboptimum developmental outcome. Maternal seafood consumption of less than 340 g per week in pregnancy did not protect children from adverse outcomes; rather, we recorded beneficial effects on child development with maternal seafood intakes of more than 340 g per week, suggesting that advice to limit seafood consumption could actually be detrimental. These results show that risks from the loss of nutrients were greater than the risks of harm from exposure to trace contaminants in 340 g seafood eaten weekly.
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            SELENIUM AS AN INTEGRAL PART OF FACTOR 3 AGAINST DIETARY NECROTIC LIVER DEGENERATION

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              Inhibition of the human thioredoxin system. A molecular mechanism of mercury toxicity.

              Mercury toxicity mediated by different forms of mercury is a major health problem; however, the molecular mechanisms underlying toxicity remain elusive. We analyzed the effects of mercuric chloride (HgCl(2)) and monomethylmercury (MeHg) on the proteins of the mammalian thioredoxin system, thioredoxin reductase (TrxR) and thioredoxin (Trx), and of the glutaredoxin system, glutathione reductase (GR) and glutaredoxin (Grx). HgCl(2) and MeHg inhibited recombinant rat TrxR with IC(50) values of 7.2 and 19.7 nm, respectively. Fully reduced human Trx1 bound mercury and lost all five free thiols and activity after incubation with HgCl(2) or MeHg, but only HgCl(2) generated dimers. Mass spectra analysis demonstrated binding of 2.5 mol of Hg(2+) and 5 mol of MeHg(+)/mol of Trx1 with the very strong Hg(2+) complexes involving active site and structural disulfides. Inhibition of both TrxR and Trx activity was observed in HeLa and HEK 293 cells treated with HgCl(2) or MeHg. GR was inhibited by HgCl(2) and MeHg in vitro, but no decrease in GR activity was detected in cell extracts treated with mercurials. Human Grx1 showed similar reactivity as Trx1 with both mercurial compounds, with the loss of all free thiols and Grx dimerization in the presence of HgCl(2), but no inhibition of Grx activity was observed in lysates of HeLa cells exposed to mercury. Overall, mercury inhibition was selective toward the thioredoxin system. In particular, the remarkable potency of the mercury compounds to bind to the selenol-thiol in the active site of TrxR should be a major molecular mechanism of mercury toxicity.
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                Author and article information

                Contributors
                nick.ralston@und.edu
                Journal
                Biol Trace Elem Res
                Biol Trace Elem Res
                Biological Trace Element Research
                Springer US (New York )
                0163-4984
                1559-0720
                13 October 2015
                13 October 2015
                2016
                : 171
                : 262-269
                Affiliations
                University of North Dakota, Grand Forks, ND 58202 USA
                Article
                516
                10.1007/s12011-015-0516-z
                4856720
                26463749
                f34cb6ee-c7b1-410c-9ee1-0609bab2dd39
                © Springer Science+Business Media New York 2015
                History
                : 7 October 2014
                : 14 September 2015
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media New York 2016

                Biochemistry
                selenium,selenoenzymes,methylmercury,brain,seafood,fish
                Biochemistry
                selenium, selenoenzymes, methylmercury, brain, seafood, fish

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