Sponsors

Volunteers

S15 Mercury and selenium interactions: Biogeochemistry and human health

Thursday, 28 July, 2011

RS15-P1 — 11:00-12:00 and 17:30-18:30
GENETIC VARIABILITY IN SELENOPROTEINS AND MERCURY BIOMARKER MEASUREMENTS IN THE MDA AND ELEMENT COHORTS
Authors: GOODRICH, Jaclyn M.1, WANG, Yi2, CANTONWINE, David2, GILLESPIE, Brenda3, WERNER, Robert4, SANCHEZ, Brisa N.3, HERNANDEZ-AVILA, Mauricio5, HU, Howard2, TELLEZ-ROJO, Martha M.6, FRANZBLAU, Alfred2
(1) Dept. of Environmental Health Sciences, University of Michigan School of Public Health , gaydojac@umich.edu; (2) Dept. of Environmental Health Sciences, University of Michigan School of Public Health; (3) Dept. of Biostatistics, University of Michigan School of Public Health; (4) Dept. of Physical Medicine and Rehabilitation, University of Michigan; (5) Ministry of Health, Districto Federal, Mexico; (6) Dept. of Statistics, Center for Evaluation Research and Surveys, National Institute of Public Health, Cuermavaca, Morelos, Mexico;

Mercury risk assessment is complicated by variability of toxicokinetic parameters, distribution to established biomarkers of exposure (hair, blood, urine), and interaction with elements such as selenium. This work hypothesizes that polymorphisms in key regulatory and coding regions of selenoprotein genes will influence mercury accumulation as assessed by biomarker measurements and biomarker distribution (e.g. hair to blood ratio) in two epidemiological cohorts. Five selenoprotein polymorphisms (rs4902346, rs2737844, rs713041, rs3877899, rs7579) were genotyped and total mercury levels were measured in biomarker samples (blood, hair, urine) from 350 Mexican mother-child pairs of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort. Likewise, four polymorphisms (rs713041, rs3877899, rs7579, rs1050450) were genotyped, and urine and hair mercury levels were obtained from 450 dental professionals of the Michigan Dental Association (MDA). Analysis of variance tests compared mean biomarker mercury levels in the ELEMENT and MDA cohorts and mean biomarker ratios (hair:blood, blood:urine) in the ELEMENT children across genotype categories for each polymorphism. Statistically different ratios of blood to urine mercury levels were observed among ELEMENT children with two copies of the major allele for a polymorphism in selenoprotein P1 (SEPP1, rs3877899), a protein known to bind mercury via its selenocysteine residues, compared to children with at least one copy of the variant allele (3.53±3.19 vs. 4.62±3.8; p=0.03). While not attaining statistical significance, in the MDA cohort, genotype of the same polymorphism trended towards modification of the relationship between fish consumption and hair mercury as assessed by linear regression. Another polymorphism in the regulatory region of SEPP1 (rs7579) significantly modified the relationship between fish consumption and hair mercury (p<0.01 for interaction) and may also modify the association between dental amalgam and urine mercury (p=0.08). This preliminary work suggests that polymorphisms in selenoproteins may influence the accumulation of mercury in the body and its distribution to various biomarkers. Future work on mercury-selenium interactions in human populations should consider the role of selenoproteins and inter-individual variability in the genes encoding these protective proteins.

RS15-P2 — 11:00-12:00 and 17:30-18:30
PROTECTION BY COMBINATION THERAPY (NAC + ZN + SE) AGAINST DIMETHYLMERCURY INDUCED OXIDATIVE STRESS - A PROTECTIVE APPROACH
Author: MITTAL, DEEPAK1
(1) JIWAJI UNIVERSITY, GWALIOR, deepakmittal05@gmail.com

Environmental pollution by heavy metals is a red-hot issue. It is being studied from many points of view, as it is not only an environmental problem but also a public health matter. Metals have been mined and used since ancient times. Metals are highly persistent and thus extremely harmful to living beings because of their bioconcentration, bioaccumulation and biomagnification in food chain. Mercury is such a toxic non-radioactive, volatile heavy metal which is ubiquitous pollutant that mainly affects various body systems particularly CNS, hepatic, renal, hametopoietic and crosses blood brain barrier. The basis of mercury toxicity is undoubtedly multifactorial. The present investigation was conducted to assess the effects of thiol chelators (NAC & DTT) along with antioxidants (Zn & Se) in liver, kidney, brain and blood. Efforts have been made to minimize the oxidative stress and toxic effects caused by mercury. Male rats of Sprague Dawley strain were administered a single dose of dimethylmercury (10 mg/kg, p.o.). Results revealed a significant rise in AST, ALT, ALP activities, bilirubin, urea and creatinine concentration where as albumin level was decreased in serum. However, a significant rise in LPO with a concomitant decrease in GSH was observed. An appreciable fall was observed in AChE in different regions of brain. These parameters were restored considerably with NAC when compared to DTT. To further enhance the efficacy of NAC, it was supplemented with Zn & Se. Results reveals that NAC+ Zn+ Se proved to be the most efficacious when compared to other treated groups in mobilizing mercury retention and helped in recovery of biochemical variables to a considerable extent. These findings were further substantiated by histopathological observations, ultrastructural changes and molecular aspects by DNA damage study.

RS15-P3 — 11:00-12:00 and 17:30-18:30
PROTECTION BY COMBINATION THERAPY (NAC + ZN + SE) AGAINST DIMETHYLMERCURY INDUCED OXIDATIVE STRESS - A PROTECTIVE APPROACH
Author: MITTAL, DEEPAK1
(1)JIWAJI UNIVERSITY, GWALIOR, deepakmittal05@gmail.com

Environmental pollution by heavy metals is a red-hot issue. It is being studied from many points of view, as it is not only an environmental problem but also a public health matter. Metals have been mined and used since ancient times. Metals are highly persistent and thus extremely harmful to living beings because of their bioconcentration, bioaccumulation and biomagnification in food chain. Mercury is such a toxic non-radioactive, volatile heavy metal which is ubiquitous pollutant that mainly affects various body systems particularly CNS, hepatic, renal, hametopoietic and crosses blood brain barrier. The basis of mercury toxicity is undoubtedly multifactorial. The present investigation was conducted to assess the effects of thiol chelators (NAC & DTT) along with antioxidants (Zn & Se) in liver, kidney, brain and blood. Efforts have been made to minimize the oxidative stress and toxic effects caused by mercury. Male rats of Sprague Dawley strain were administered a single dose of dimethylmercury (10 mg/kg, p.o.). Results revealed a significant rise in AST, ALT, ALP activities, bilirubin, urea and creatinine concentration where as albumin level was decreased in serum. However, a significant rise in LPO with a concomitant decrease in GSH was observed. An appreciable fall was observed in AChE in different regions of brain. These parameters were restored considerably with NAC when compared to DTT. To further enhance the efficacy of NAC, it was supplemented with Zn & Se. Results reveals that NAC+ Zn+ Se proved to be the most efficacious when compared to other treated groups in mobilizing mercury retention and helped in recovery of biochemical variables to a considerable extent. These findings were further substantiated by histopathological observations, ultrastructural changes and molecular aspects by DNA damage study.

RS15-P4 — 11:00-12:00 and 17:30-18:30
SELENIUM HAS A PROTECTIVE EFFECT AGAINST MERCURY TOXICITY IN TROPICAL COASTAL AQUATIC SPECIES
Author: KEHRIG, Helena A.1
(1) IBCCF-UFRJ, kehrig@biof.ufrj.br

Selenium (Se) is nutritionally important as an essential trace-element for all life forms that have nervous systems, but is harmful at slightly higher concentrations. Se reportedly protects mammals against the toxic effects of mercury (Hg). Hg has no known normal metabolic function and its presence in living organisms is potentially hazardous. Hg accumulates in the aquatic food web. It is the chief exposure route for wildlife and humans. The Se:Hg molar ratios approaching or exceeding 1:1 is thought to provide Se-dependent Health Benefits (Se-HB) as protective against Hg toxicity. Evaluation of the health risk posed by Hg exposure from seafood consumption requires concurrent consideration of Se content in the particular species. Se and Hg concentrations, based on a wet weight basis, were evaluated in 531 individuals’ muscle tissue of 179 predatory fish (PF), 60 non-predatory fish (NPF), 24 squids (MC), 153 mussels (MB), 70 shrimps (AC1) and 45 crabs (AC2) from a south-eastern Brazilian coast. These aquatic species are widely distribution in this region and are also often consumed by the human population. All species presented Se in muscle below the maximum allowable selenium concentrations, 2.0 mg/kg, proposed by Lemly (2007). Only five PF individuals presented Hg in muscle above the maximum permissible limit of 0.50 mg/kg wet wt. established for human consumption of aquatic species by WHO. As Hg exposure from fish consumption has been the focus of this study, the molar ratio between Se and Hg has been investigated. Se was in molar excess of Hg in almost all species, indicating that substantial Se was available to counter the Hg that was also presented in them. Only 7 individuals presented the Se:Hg of less than 1. Se:Hg might decline with increasing fish length, possibly reducing Se protection in larger fish. The relationship between Se:Hg and length was poor and significant (r=-0.324; p<0.0001). Se-HB value was calculated as Kaneko and Ralston (2007) to better describe and integrate Se-specific nutritional benefits in relation to potential Hg-exposure risks presented by these species evaluated. As a result of their rich Se and low Hg contents, all aquatic species presented Se-HBV higher than 1, suggesting that they have Se to potentially protect them and their consumers against Hg toxicity. Centropomus undecimalis (common snook) and Paralonchurus brasiliensis (banded croaker) had the most favorable Se-HBV.

RS15-P5 — 11:00-12:00 and 17:30-18:30
RISK AND POLICY IMPLICATIONS OF SELENIUM – MERCURY RATIOS: VARIABILITY WITHIN AND AMONG FISH SPECIES.
Author: BURGER, Joanna1
(1) Rutgers University and CRESP, burger@biology.rutgers.edu

Selenium (Se) plays a protective role against mercury (Hg) toxicity with uncertainty about both mechanisms and the protection conferred by different Se:Hg molar ratios. The general applicability of using molar ratios, rather than concentrations or intakes in risk assessment and risk management is an important policy issue. In this paper we report that the selenium/mercury molar ratios vary considerably among and within fish species. We examined the molar ratios for individual fish (as opposed to mean ratios by species) for saltwater fish from the Aleutians and New Jersey. Cold water fish from the Aleutians are prominent commercial species (e.g., Pacific Cod, Halibut) while the recreational-caught New Jersey fish included a wide range of coastal species. We analyzed species with low mercury levels, as well as species with high levels. Any ratio is very sensitive to the denominator, such that the Se:Hg ratio depended more on Hg concentration than on Se. However some fish with low Hg concentration also had low Se:Hg ratios. There is considerable inter-individual variation in molar ratios, such that the molar ratios of means may not be representative. Mercury levels varied greatly with fish size while selenium was less variable. The data indicate that considerable attention will need to be directed toward variations and variances, as well as the mechanisms of the interaction of selenium and mercury before risk assessment and risk management policies can use this information.

RS15-P6 — 11:00-12:00 and 17:30-18:30
SELENIUM FROM OCEAN FISH PREVENTS METHYLMERCURY TOXICITY
Author: RAYMOND, Laura1
(1) Energy & Environmental Research Center / UND, lraymond@undeerc.org

Supplemental selenium (Se) has been known to counteract mercury (Hg) toxicity since 1967, but the mechanisms of this effect have only recently become clear. Methylmercury (MeHg) is a highly specific irreversible inhibitor of Se-dependent enzymes (Se-enzymes). Supplemental dietary Se replenishes Se lost to MeHg binding, thereby maintaining normal Se-enzyme activities. Our prior animal studies have shown that the normal range of dietary Se (as sodium selenite) is effective in preventing MeHg toxicity. Since ocean fish are among the richest sources of dietary Se, we hypothesized that their Se contents would protect against the adverse effects expected with MeHg exposures from seafood consumption. In this study, 120 weanling male Long Evans rats were fed low Se torula yeast based diets for 5 weeks to deplete their tissue Se reserves. The diets were then modified to contain either low or high MeHg (0.5 or 50 nmol MeHg/g) and either sodium selenite (~0.1, 1.0, or 10 nmol Se/g) or Se from delipidated protein isolates from bigeye tuna, swordfish, or mako shark (3.5, 2.3, and 2.1 nmol/g respectively) added as 10% of the total diet in place of an equivalent amount of torula yeast protein; (2 Hg levels x 6 Se diets = 12 dietary treatments, 10 rats per group). Contributions of additional MeHg in the tuna, swordfish, and shark supplemented diets were 1.6, 2.3, and 3.6 nmol MeHg/g respectively. Rats fed high MeHg, low Se diets showed growth inhibition after 4 weeks, and hind limb crossing after 9 weeks, with brain GPx activity reduction to less than 30% of Se adequate levels. Rats fed all other dietary treatments grew normally and did not show symptoms of MeHg toxicity even though GPx activity in the brains of rats fed Se deficient diets were reduced to less than 70% of Se adequate levels. Isoprostane levels were ~4 fold higher in brains of rats with MeHg impaired GPx activities. The results from this study indicate that Se from the fish diets was effective in maintaining adequate brain GPx levels and in preventing MeHg toxicity even though the fish provided additional MeHg.

Thursday, 28 July, 2011