Selenium and mercury levels in rat liver slices co-treated with diphenyl diselenide and methylmercury.

Organoseleno-compounds have been investigated for its beneficial effects against methylmercury toxicity. In this way, diphenyl diselenide (PhSe)2 was demonstrated to decrease Hg accumulation in mice, protect against MeHg-induced mitochondrial dysfunction, and protect against the overall toxicity of this metal. In the present study we aimed to investigate if co-treatment with (PhSe)2 and MeHg could decrease accumulation of Hg in liver slices of rats. Rat liver slices were co-treated with (PhSe)2 (0.5; 5 µM) and/or MeHg (25 µM) for 30 min at 37 °C and Se and Hg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in the slices homogenate, P1 fraction, mitochondria and incubation medium. Co-treatment with (PhSe)2 and MeHg did not significantly alter Se levels in any of the samples when compared with compounds alone. In addition, co-treatment with (PhSe)2 and MeHg did not decrease Hg levels in any of the samples tested, although, co-incubation significantly increased Hg levels in homogenate. We suggest here that (PhSe)2 could exert its previously demonstrated protective effects not by reducing MeHg levels, but forming a complex with MeHg avoiding it to bind to critical molecules in cell.

Methylmercury Increases and Eicosapentaenoic Acid Decreases the Relative Amounts of Arachidonic Acid-Containing Phospholipids in Mouse Brain.

The membrane phospholipid composition in mammalian brain can be modified either by nutrients such as dietary fatty acids, or by certain toxic substances such as methylmercury (MeHg), leading to various biological and toxic effects. The present study evaluated the effects of eicosapentaenoic acid (EPA) and MeHg on the composition of the two most abundant membrane phospholipid classes, i.e., phosphatidylcholines (PtdCho) and phosphatidylethanolamines (PtdEtn), in mouse brain by using a two-level factorial design. The intact membrane PtdCho and PtdEtn species were analyzed by liquid chromatography-mass spectrometry. The effects of EPA and MeHg on the PtdCho and PtdEtn composition were evaluated by principal component analysis and ANOVA. The results showed that EPA and MeHg had different effects on the composition of membrane PtdCho and PtdEtn species in brain, where EPA showed strongest impact. EPA led to large reductions in the levels of arachidonic acid (ARA)-containing PtdCho and PtdEtn species in brain, while MeHg tended to elevate the levels of ARA-containing PtdCho and PtdEtn species. EPA also significantly increased the levels of PtdCho and PtdEtn species with n-3 fatty acids. Our results indicate that EPA may to some degree counteract the alterations of the PtdCho and PtdEtn pattern induced by MeHg, and thus alleviate the MeHg neurotoxicity in mouse brain through the inhibition of ARA-derived pro-inflammatory factors. These results may assist in the understanding of the interaction between MeHg, EPA and phospholipids, as well as the risk and benefits of a fish diet.

Neuroprotective Effect of Portulaca oleraceae Ethanolic Extract Ameliorates Methylmercury Induced Cognitive Dysfunction and Oxidative Stress in Cerebellum and Cortex of Rat Brain.

Methylmercury (MeHg) is highly toxic, and its principal target tissue in human is the nervous system, which has made MeHg intoxication a public health concern for many decades. Portulaca oleraceae (purslane), a member of the Portulacaceae family, is widespread as a weed and has been ranked the eighth most common plant in the world. In this study, we sought for potential beneficial effects of Portulaca oleracea ethanolic extract (POEE) against the neurotoxicity induced by MeHg in cerebellum and cortex of rats. Male Wistar rats were administered with MeHg orally at a dose of 5 mg/kg b.w. for 21 days. Experimental rats were given MeHg and also administered with POEE (4 mg/kg, orally) 1 h prior to the administration of MeHg for 21 days. After MeHg exposure, we determine the mercury concentration by atomic absorption spectroscopy (AAS); mercury content was observed high in MeHg-induced group. POEE reduced the mercury content. We also observed that the activities of catalase, superoxide dismutase, glutathione peroxidase, and the level of glutathione were reduced. The levels of glutathione reductase and thiobarbituric acid reactive substance were found to be increased. The above biochemical changes were found to be reversed with POEE. Behavioral changes like decrease tail flick response, longer immobility time, and decreased motor activity were noted down during MeHg exposure. POEE pretreatment offered protection from these behavioral changes. MeHg intoxication also caused histopathological changes in cerebellum and cortex, which was found to be normalized by treatment with POEE. The present results indicate that POEE has protective effect against MeHg-induced neurotoxicity.

Methylmercury-induced oxidative stress in rainbow trout (Oncorhynchus mykiss) liver: ameliorating effect of vitamin C.

The present study was undertaken to evaluate methylmercury-induced alterations in hepatic enzymes and oxidative stress markers in liver tissue of rainbow trout (Oncorhynchus mykiss) by using a perfusion method, and to explore possible protective effect of vitamin C against these alterations. Forty-eight fish were divided into six groups containing control, test, and amelioration groups. The liver of fish in the test groups were exposed to different doses of methylmercury, i.e., 0.6, 1.2, and 2.4 µg L(-1), respectively, for 120 min. In the amelioration group, liver was treated with vitamin C (17.2 µg L(-1)) along with high dose (2.4 µg L(-1)) of methylmercury. The results of the present study showed that exposure with 0.6, 1.2, and 2.4 µg L(-1) of methylmercury significantly increased (p < 0.05) hepatic enzyme activities (alanine transaminase (ALT), aspartate transaminase (AST), and Lactate dehydrogenase (LDH)) and malondialdehyde (MDA) level, as a marker of lipid peroxidation. On the other hand, the concentration of reduced glutathione (GSH) and total antioxidant capacity of the liver decreased (p < 0.05) in the methylmercury-exposed groups when compared to the control group. Pearson's correlation analysis revealed a positive correlation between MDA concentration and ALT, AST, and LDH activities in the methylmercury groups, suggesting that the enhanced lipid peroxidation may be linked to hepatic damage caused by methylmercury. Treatment with vitamin C in methylmercury-exposed group led to a significant decrease (p < 0.05) in MDA concentration and hepatic enzyme activities and significant increase (p < 0.05) in levels of GSH and total antioxidant capacity. The values of measured parameters in the methylmercury + vitamin C group were comparable to those of the control group. The results of the present study demonstrated that methylmercury exposure induces oxidative stress in the liver of rainbow trout and treatment with vitamin C can protect fish liver against this oxidative insult.

Exposición al metilmercurio en la población general; toxicocinética; diferencias según el sexo, factores nutricionales y genéticos / Methylmercury exposure in the general population; toxicokinetics; differences by gender, nutritional and genetic factors

El mercurio es un tóxico ambiental que causa numerosos efectos adversos en la salud humana y en los ecosistemas naturales. Los factores que determinan la aparición de efectos adversos y su severidad son entre otros: la forma química del mercurio (elemental, inorgánico, orgánico), la dosis, la edad, la duración de la exposición, la vía de exposición y los factores ambientales, nutricionales y genéticos. En el ciclo acuático del mercurio, una vez que se ha depositado, se transforma en metilmercurio por la acción de determinadas bacterias sulfato reductoras y se bioacumula en los organismos acuáticos incorporándose a la cadena trófica de alimentos. El contenido de metilmercurio es mayor en las especies depredadoras de mayor tamaño y que viven más años como el emperador, pez espada, tiburón, atún o marlín. El metilmercurio se halla unido a las proteínas del pescado por lo que no se elimina mediante la limpieza ni el cocinado del mismo. El feto en desarrollo y los niños pequeños son los más vulnerables a los efectos neurotóxicos del metilmercurio procedente de la ingesta de pescado contaminado. El metilmercurio se absorbe en el tracto gastrointestinal y atraviesa la barrera hematoencefálica y la placenta. Algunos componentes de la dieta como los ácidos grasos poliinsaturados, el selenio, la fibra, los compuestos tiol, algunos fitoquímicos y otros nutrientes pueden modificar la bioaccesibilidad del mercurio y su toxicidad. Además de los factores ambientales, los factores genéticos pueden influir en la toxicidad del mercurio y explicar parte de la vulnerabilidad individual (AU)

Mercury is an environmental toxicant that causes numerous adverse effects on human health and natural ecosystems. The factors that determine the existance of adverse effects, as well as their severity are, among others: the chemical form of mercury (elemental, inorganic, organic), dosis, age, period of exposure, pathways of exposure and environmental, nutritional and genetic factors. In the aquatic cycle of mercury, once it has been deposited, it is transformed into methylmercury due to the action of certain sulphate-reducing bacteria, which bioaccumulates in the aquatic organisms and moves into the food chain. The methylmercury content of large, long-lived fish such as swordfish, shark, tuna or marlin, is higher. Methylmercury binds to protein in fish and is therefore not eliminated by cleaning or cooking the fish. Fetuses and small children are more vulnerable to the neurotoxic effects of methylmercury from the consumption of contaminated fish. Methylmercury is absorbed in the gastrointestinal tract and crosses the blood-brain barrier and the placenta. The intake of certain dietary components such as polyunsaturated fatty acids, selenium, fiber, thiol compounds, certain phytochemicals and other nutrients can modify methylmercury bioaccesibility and its toxicity. Apart from environmental factors, genetic factors can influence mercury toxicity and explain part of the individual vulnerability (AU)

Selenium prevents downregulation of antioxidant selenoprotein genes by methylmercury.

Selenium (Se) is an essential nutrient required by Se-dependent proteins, termed selenoproteins. The selenoprotein family is small but diverse and includes key proteins in antioxidant, redox signaling, thyroid hormone metabolism, and protein folding pathways. Methylmercury (MeHg) is a toxic environmental contaminant that affects seafood safety. Selenium can reduce MeHg toxicity, but it is unclear how selenoproteins are affected in this interaction. In this study we explored how Se and MeHg interact to affect the mRNA expression of selenoprotein genes in whole zebrafish (Danio rerio) embryos. Embryos were obtained from adult zebrafish fed MeHg with or without elevated Se in a 2×2 factorial design. The embryo mRNA levels of 30 selenoprotein genes were then measured. These genes cover most of the selenoprotein families, including members of the glutathione peroxidase (GPX), thioredoxin reductase, iodothyronine deiodinase, and methionine sulfoxide reductase families, along with selenophosphate synthetase 2 and selenoproteins H, J-P, T, W, sep15, fep15, and fam213aa. GPX enzyme activity and larval locomotor activity were also measured. We found that around one-quarter of the selenoprotein genes were downregulated by elevated MeHg. These downregulated genes were dominated by selenoproteins from antioxidant pathways that are also susceptible to Se-deficiency-induced downregulation. MeHg also decreased GPX activity and induced larval hypoactivity. Elevated Se partially prevented MeHg-induced disruption of selenoprotein gene mRNA levels, GPX activity, and larval locomotor activity. Overall, the MeHg-induced downregulation and subsequent rescue by elevated Se levels of selenogenes regulated by Se status suggest that Se deficiency is a contributing factor to MeHg toxicity.

Prenatal exposure to methylmercury and LCPUFA in relation to birth weight.

BACKGROUND: Epidemiologic studies have been inconclusive regarding the impact of coexposure to long chain polyunsaturated fatty acids (LCPUFA) and methylmercury (MeHg) from fish consumption during pregnancy on measures of fetal development. OBJECTIVES: We evaluated the association between birth weight and prenatal maternal LCPUFA status and MeHg exposure in the Republic of Seychelles. METHODS: We measured LCPUFA in maternal whole blood collected at 28 weeks of gestation and following delivery and MeHg in maternal hair obtained at delivery. There were 230 births with complete data on birth weight and covariates. Multiple linear regression models controlled for infant sex, gestational age, maternal age, smoking during pregnancy, intrapartum weight gain, prepregnancy body mass index, maternal socioeconomic status, parity, gestational diabetes, and alcohol use during pregnancy. RESULTS: The average birth weight was 3252 g (range 1654-4450) and the average gestational age was 39 weeks (range 34-41). Prenatal MeHg exposure and maternal LCPUFA status were not associated with birth weight. Infant sex and length of gestation were the only predictors, with male sex and increased gestational age consistently associated with greater birth weight. CONCLUSIONS: These findings do not support a relationship between prenatal exposure to LCPUFA and/or MeHg from fish consumption and birth weight.

Cerebral gene expression and neurobehavioural responses in mice pups exposed to methylmercury and docosahexaenoic acid through the maternal diet.

Methylmercury (MeHg) is an environmental neurotoxicant with adverse effects particularly noted in the developing brain. The main source of MeHg exposure is seafood. However, fish is also an important source of n-3 fatty acids such as docosahexaenoic acid (DHA) which has neuroprotective effects, and which plays an important role during the prenatal development of the central nervous system. The aim of the present study was to examine the effects of DHA and MeHg individually, and in combination, on development using accumulation, behavioural and transcriptomic endpoints in a mammalian model. Analyses were performed on 15 day old mice which had been exposed to varying levels of DHA (8 or 24 mg/kg) and/or MeHg (4 mg/kg) throughout development via the maternal diet. Supplementation of the maternal diet with DHA reduced MeHg accumulation in the brain. An accelerated development of grasping reflex was seen in mice offspring in the 'MeHg+high DHA' group when compared to 'MeHg' and 'control'. Exposure to MeHg and DHA had an impact on cerebral gene expression as assessed by microarray and qPCR analysis. The results from the present study show the potential of DHA for alleviating toxicity caused by MeHg. This information may contribute towards refining risk/benefit assessment of seafood consumption and may enhance understanding of discrepancies between epidemiological studies of MeHg neurodevelopmental toxicity.

Mangiferin attenuates methylmercury induced cytotoxicity against IMR-32, human neuroblastoma cells by the inhibition of oxidative stress and free radical scavenging potential.

Mangiferin (MGN), a C-glucosylxanthone was investigated for its ability to protect against methylmercury (MeHg) induced neurotoxicity by employing IMR-32 (human neuroblastoma) cell line. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and clonogenic cell survival assays confirmed the efficacy of MGN supplementation in attenuating MeHg-induced cytotoxicity. Pre-treatment with MGN significantly (p<0.01) inhibited MeHg-induced DNA damage (micronuclei, olive tail moment and % tail DNA) thereby demonstrating MGN's antigenotoxic potential. Also, pre-treatment with MGN significantly reduced MeHg-induced oxidative stress, intra-cellular Ca(2+) influx and inhibited depolarization of mitochondrial membrane. MGN pre-treated cells demonstrated a significant (p<0.05) increase in the GSH and GST levels followed by a significant (p<0.05) decrease in malondialdehyde (MDA) formation. In addition, inhibition of MeHg induced apoptotic cell death by MGN was demonstrated by microscopic, Annexin-V FITC and DNA fragmentation assays and further confirmed by western blot analysis. The present findings indicated the protective effect of MGN against MeHg induced toxicity, which may be attributed to its anti-genotoxic, anti-apoptotic and anti-lipid peroxidative potential plausibly because of its free radical scavenging ability, which reduced the oxidative stress and in turn facilitated the down-regulation of mitochondrial apoptotic signalling pathways.

Methyl mercury inhibits short-circuit current and Cl- influx across isolated epipodite of European lobster (Homarus gammarus).

The effect of methyl mercuric chloride (MeHg) on short-circuit current (I(SC)) was studied in the isolated perfused epipodite preparation from the branchial chamber of European lobster (Homarus gammarus) acclimated to dilute seawater. When applied at the apical surface, 0.2, 1.0 and 3.0 microM MeHg depressed I(SC) by a 26%, 81% and 98%, respectively. The half-maximal inhibitory concentration (IC(50)) of apically applied MeHg was 0.6 microM. Basolaterally added MeHg (3.0 microM) had no effect on I(SC), whereas addition of the specific Na(+),K(+)-ATPase inhibitor ouabain (1.5 mM) reduced I(SC) by approximately 90%. Ouabain effects were reversible, and I(SC) fully recovered upon removal of ouabain. The MeHg-induced block of I(SC) was partially reversed by the reducing agent, 1,4-dithiothreitol, suggesting that the formation of S-Hg-S bridges is important in the inhibitory mechanism. A significant reduction of I(SC) and conductance occurred when low Na(+) and Cl(-) salines were substituted. Furthermore, in the low Na(+) saline, J(Cl)(A-->B) fluxes were reduced by about 50%. In the highly conductive epipodite epithelium, coupling of Na(+) and Cl(-) fluxes was suggested. The effects of MeHg on I(SC) in the lobster epipodite are attributed to inhibition of an apical Cl(-) influx.

Mercury toxicity and the mitigating role of selenium.

Mercury is a well-known environmental toxicant, particularly in its most common organic form, methylmercury. Consumption of fish and shellfish that contain methylmercury is a dominant source of mercury exposure in humans and piscivorous wildlife. Considerable efforts have focused on assessment of mercury and its attendant risks in the environment and food sources, including the studies reported in this issue. However, studies of mercury intoxication have frequently failed to consider the protective effects of the essential trace element, selenium. Mercury binds to selenium with extraordinarily high affinity, and high maternal exposures inhibit selenium-dependent enzyme activities in fetal brains. However, increased maternal dietary selenium intakes preserve these enzyme activities, thereby preventing the pathological effects that would otherwise arise in their absence. Recent evidence indicates that assessments of mercury exposure and tissue levels need to consider selenium intakes and tissue distributions in order to provide meaningful risk evaluations.

Salicylic acid triggers genotoxic adaptation to methyl mercuric chloride and ethyl methane sulfonate, but not to maleic hydrazide in root meristem cells of Allium cepa L.

Salicylic acid (SA), 0.01 mM, a signalling phytohormone, was tested for induction of adaptive response against genotoxicity of methyl mercuric chloride (MMCl), 0.013 mM; ethylmethane sulfonate (EMS), 2.5 mM, or maleic hydrazide (MH), 5 mM, in root meristem cells of Allium cepa. Induction of adaptive response to EMS by hydrogen peroxide (H2O2), 1 mM, and yet another secondary signal molecule was tested for comparison. Assessed by the incidence of mitoses with spindle and/or chromosome aberration and micronucleus, the findings provided evidence that SA-conditioning triggered adaptive response against the genotoxic-challenges of MMCl and EMS, but failed to do so against MH. H2O2, which is known to induce adaptive response to MMCl and MH, failed to induce the same against EMS in the present study. The findings pointed to the possible role of signal transduction in the SA-induced adaptive response to genotoxic stress that perhaps ruled out an involvement of H2O2.

Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2.

Methylmercury (MeHg) readily crosses cell membrane barriers to reach its target tissue, the brain. Although it is generally assumed that this rapid transport is due to simple diffusion, recent studies have demonstrated that MeHg is transported as a hydrophilic complex, and possibly as an L-cysteine complex on the ubiquitous L-type large neutral amino acid transporters (LATs). To test this hypothesis, studies were carried out in Xenopus laevis oocytes expressing two of the major L-type carriers in humans, LAT1-4F2 heavy chain (4F2hc) and LAT2-4F2hc. Oocytes expressing LAT1-4F2hc or LAT2-4F2hc demonstrated enhanced uptake of [(14)C]MeHg when administered as the L-cysteine or D,L-homocysteine complexes, but not when administered as the D-cysteine, N -acetyl-L-cysteine, penicillamine or GSH complexes. Kinetic analysis of transport indicated that the apparent affinities ( K (m)) of MeHg-L-cysteine uptake by LAT1 and LAT2 (98+/-8 and 64+/-8 microM respectively) were comparable with those for methionine (99+/-9 and 161+/-11 microM), whereas the V (max) values were higher for MeHg-L-cysteine, indicating that it may be a better substrate than the endogenous amino acid. Uptake and efflux of [(3)H]methionine and [(14)C]MeHg-L-cysteine were trans -stimulated by leucine and phenylalanine, but not by glutamate, indicating that MeHg-L-cysteine is both a cis - and trans -substrate. In addition, [(3)H]methionine efflux was trans -stimulated by leucine and phenylalanine even in the presence of an inwardly directed methionine gradient, demonstrating concentrative transport by both LAT1 and LAT2. The present results describe a major molecular mechanism by which MeHg is transported across cell membranes and indicate that metal complexes may form a novel class of substrates for amino acid carriers. These transport proteins may therefore participate in metal ion homoeostasis and toxicity.

Differences in the growth inhibition of cultured K-562 cells by selenium, mercury or cadmium in two tissue culture media (RPMI-1640, Ham's F-10).

Effects of some metals on the growth of cultured human erythroleukemia K-562 cells were investigated when grown in two different types of media based upon RPMI-1640 or Ham's F-10. The study on proliferation, using RPMI-1640 supplemented with sodium selenite, selenomethionine, mercuric chloride, methylmercuric chloride and cadmium nitrate showed no inhibition of growth at concentrations of 2.5, 25, 25, 2.5 and 25 microM, while at 75, 250, 50, 5 and 50 microM toxicity was apparent. Selenite at 5-50 microM and selenomethionine at 50-100 microM inhibited the growth. In Ham's F-10 supplemented with the same compounds no inhibition was found at concentrations of 5, 10, 25, 1 and 50 microM, while at 50, 100, 50, 5 and 75 microM toxic effects were noted. Selenite 10 microM and selenomethionine 25-50 microM inhibited the proliferation. Measurements of trace element levels in pellets of K-562 cells grown in RPMI-1640 or Ham's F-10 unveiled higher cell contents of cadmium and selenium in cells grown in RPMI-1640, being consistent with higher concentrations of these elements in that medium. Manganese and mercury concentrations were higher in cells grown in Ham's F-10 correlating with a higher medium concentration of these elements. The growth responses and cellular uptake differed between the metals and the selenocompounds and although extrapolating the results to humans is difficult the selenium exposures were in approximately the same order of magnitude as in human exposures. The compounds could be ranked according to decreasing toxicity as: methylmercuric chloride > mercuric chloride, cadmium nitrate, sodium selenite > selenomethionine.

Lack of effect of methylmercury exposure from birth to adulthood on information processing speed in the monkey.

Although it is established that developmental methylmercury exposure produces severe motor and sensory impairment, the effect on cognitive function is less clear. To explore this issue, monkeys with robust methylmercury-induced deficits in visual, auditory, and somatosensory function were tested on a series of tasks assessing central processing speed, which is highly correlated with intelligence in humans. Five monkeys (Macaca fascicularis) were dosed from birth to 7 years of age with 50 micrograms/kg/day of mercury as methylmercuric chloride. Blood mercury levels were stable at 0.8-1.1 micrograms/g until cessation of dosing. When they were 20 years old, these monkeys and four age- and rearing-matched controls were tested on a series of simple and complex reaction time tasks. The monkey sat in a primate chair with a stainless steel bar centered at waist height. Four push buttons equidistant from the steel bar were mounted on a vertical Plexiglas panel in front of the monkey. The monkey was required to make contact with the bar, then release the bar and push the appropriate button in response to a change in stimulus conditions. For the first task (simple reaction time), the monkey was required to respond on a button when it changed from unlit to red. The monkey then performed a sequence of complex reaction time tasks: two-button, four-button, and several tasks of increasing complexity using four buttons and multiple colors. For each task, the latency to release the bar after the stimulus change (central processing speed) and to move the hand from the bar to the button (motor speed) were determined. Lastly, the monkey was required to make the quickest possible motor response on the simple reaction time task. There were no differences between groups on any aspect of the experiment. These data provide further evidence for absence of cognitive impairment in monkeys exposed developmentally to methylmercury.

The relationship between gamma-glutamyl transpeptidase and Hg levels in Se/Hg antagonism in mouse liver and kidney.

The gamma-glutamyl transpeptidase (gamma-GT) activity and Hg concentrations were studied in Se/Hg antagonism in mouse liver and kidney after treatment with methyl mercury (MM) (MM group) and MM + sodium selenite (SE) (SM group). In acute treatment (dietary doses: MM = 250 p.p.m.; SE = 90 p.p.m.; length of treatment 11 days), hepatic gamma-GT activity increased in both protected and unprotected animals with respect to controls and reached a peak after 3 days with respect to controls, its value being relatively greater in the MM group. On the contrary, renal gamma-GT decreased with time with respect to controls and was higher in the SM group at 3 and 7 days. Liver and kidney accumulation of Hg increased and decreased respectively with time, and was higher in SM groups in most cases. In chronic treatment (dietary doses: MM = 12.5 p.p.m.; SE = 9 p.p.m.; length of treatment 12 months) hepatic gamma-GT activity in the MM group was higher than in the SM group at 1.5 and 7 months, whereas the renal activity was lower at 7 months and unchanged at 1.5 and 12 months. In comparison with the acute treatment, the trend of Hg accumulation was similar in liver and different in kidney; Hg concentrations of the SM group were always greater than those of the MM group. Glutathione (GSH) in liver and non-protein SH groups (NPSH) in kidney were also measured in acutely treated animals. On the first day GSH was about 50% of the control value in both the MM and SM groups; it subsequently remained constant in the MM group, but increased to a peak at 7 days, without reaching the control value, in the SM group. Unlike the liver, renal NPSH increased in both groups on the first day, and then decreased with time without reaching the control value, SM group values always exceeding those of MM group. The modulation of gamma-GT activity in liver and kidney caused by SE suggests that the enzyme plays a role in Hg accumulation.

Selenium-mercury interaction during intestinal absorption of 75Se compounds in chicks.

The effects of inorganic (HgCl2) and organic (CH3HgCl) mercury on the intestinal absorption of Se compounds [Na2(75)SeO3, Na2(75)SeO4, L-[75Se]methionine ([75Se]Met)] were determined in 3-wk-old White Leghorn cockerels by the in vivo ligated duodenal loop procedure. The intraduodenal dose contained 0.05 microCi 75Se, 0.01 mM Se, 150 mM NaCl and 0-1.0 mM Hg. In the presence of 1 mM inorganic Hg in the intraduodenal dose, the absorption of the inorganic 75Se compounds was only about 65% of that in the control group, whereas only a slight inhibitory effect on [75Se]Met absorption was observed. Methylmercury had no effect on [75Se]selenite absorption. Precipitation of the 75Se-selenite in the intestinal lumen partly explained the direct interaction between inorganic Hg and Se compounds. Absorption of [75Se]Met and [75Se]selenite was also determined in chicks fed after hatching a purified diet supplemented with varying amounts of Hg (0-500 mg/kg) and Se (0-4 mg/kg). Dietary Hg significantly reduced the transfer of [75Se]selenite to body by enhancing the accumulation of the isotope in the intestinal tissue. Dietary Hg did not affect the absorption of [75Se]Met, but altered the whole-body distribution of this Se compound. Because interaction between Se and Hg was observed mainly between the inorganic compounds and with use of a manyfold excess of Hg over Se, the data suggest that intestinal interaction between these metals is not of great nutritional importance.

The stimulation and inhibition of the exhalation of volatile selenium.

Administration of methylmercury (1.5-24 mumol kg-1; s.c.) to female rats simultaneously with Na2 75SO3 (0.25 or 24 mumol kg-1; s.c.) causes a dose-dependent increase in the exhalation of dimethylselenide. At the low selenite dose level, exhalation of 75Se over a 24 hr period is about fourfold greater after treatment with 24 mumol kg-1 methylmercury than that (approximately 0.75% of the dose) in the controls, but excretion by other routes (urine, faeces) and the liver and kidney contents of 75Se are not affected significantly. At the higher selenite dose level (24 mumol kg-1) exhalation of 75Se is correlated with the log dose of methylmercury. The faecal and urinary excretion remains essentially unaffected, and in rats treated with 24 mumol kg-1 methylmercury the 75Se contents of the liver, kidneys and blood are reduced by 78%, 86% and 18% respectively. The effects of the alkylmercurial are not specific since, at this selenite dose level, ethylmercury increases the exhalation and decreases the liver and kidney contents of 75Se approximately to the same extent as an equimolar dose of methylmercury. In methylmercury-treated and control animals dosed with 24 mumol kg-1 Na 75SeO3 the exhalation of 75Se is inhibited to the same extent by periodate-oxidized adenosine (PAD; 15 mumol kg-1, i.p.) in the first 6 hr. Later inhibition is less pronounced in methylmercury-treated rats. Under these conditions PAD has little effect on the renal content, but increases the hepatic content of 75Se. It seems, therefore, that the methylation of selenite occurs mainly in the liver and in both control and methylmercury-treated animals, S-adenosylmethionine is the major methyl donor. It is possible that methylmercury does not affect directly the methylation enzyme system but, by competition for protein sulphydryl groups, increases the availability of the intermediary selenide anion.

Genetic variation in the susceptibility to mercury and other metal compounds in Drosophila melanogaster.

The tolerance of Drosophila melanogaster to heavy metal compounds was investigated with special emphasis on methylmercury. A pronounced variation in tolerance to CH3HgOH, HgCl2, (C2H5)3PbCl, (CH3)3SnCl, and CdCl2 was recorded between 12 wild-type strains. After ranking the tolerance of the strains with respect to the five compounds rank correlations for experiments within and between compounds were calculated. The results showed a high degree of correlation within compounds but no unequivocal indication of a correlation between compounds, indicating that different mechanisms of genetic control for tolerance were operating for the five compounds. Rank correlations for experiments with 12 different mercury, lead, tin, and cadmium compounds and the same 12 wild-type strains only indicated one significant correlated response, between tripropyltin and tributyltin. A selection experiment for tolerance to methylmercury was performed with a foundation population, synthesized from four wild-type strains, showing a high initial tolerance. One control and two levels of treatment doses were used. A distinct selection response was obtained and a high tolerance was reached particularly for the high-dose selection line after 12 generations, when the experiment ended. Genetic analysis of the tolerance indicated a dominant and polygenic inheritance. Investigation of the uptake and excretion of CH3Hg203OH showed that the level of tolerance to methylmercury was correlated with the uptake of the mercury but apparently not with the rate of excretion. Cystein increased the susceptibility to methylmercury. Inorganic mercury and trimethyl lead exhibited a synergistic toxic effect, evidently as the result of an in vitro transmethylation of mercury. A high somatic susceptibility to methylmercury also applied to the induction of nondisjunction and sex-linked recessive lethals.

Methylmercury stimulates the exhalation of volatile selenium and potentiates the toxicity of selenite.

The aim of the present experiments was to investigate whether a single dose of 24 mumol/kg methylmercuric chloride (MeHgCl) in rats can influence the effect of an equimolar dose of sodium selenite (Na2SeO3) on body weight or the exhalation of dimethylselenide, a volatile metabolic product of selenium. Due to the difference in their single-dose toxicities, only selenite depressed body weight gain, when given alone. The experiments indicated that methylmercury, irrespective of whether it was given 1-2 h before, or at the same time as sodium selenite, potentiated the effect of the latter on body weight. Methylmercury also increased the exhalation of volatile selenium, but this effect decreased when the administration of selenite was delayed.