Does the addition of ingredients affect mercury and cadmium bioaccessibility in seafood-based meals?

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.

Primary amino acids affect the distribution of methylmercury rather than inorganic mercury among tissues of two farmed-raised fish species.

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.

Methylmercury's chemistry: From the environment to the mammalian brain.

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 (R1S(e)-HgMe + R2-S(e)H ↔ R1S(e)H + R2-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.

Glutathione antioxidant system and methylmercury-induced neurotoxicity: An intriguing interplay.

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.

Reducing methylmercury accumulation in fish using Escherichia coli with surface-displayed methylmercury-binding peptides.

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.

In vitro evaluation of dietary compounds to reduce mercury bioavailability.

Mercury in foods, in inorganic form [Hg(II)] or as methylmercury (CH3Hg), 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 CH3Hg 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.

Oral exposure of pregnant rats to toxic doses of methylmercury alters fetal accumulation.

Methylmercury (CH3Hg+) 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 CH3Hg+, conjugated to cysteine (Cys; Cys-S-CH3Hg) 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-CH3Hg by maternal and fetal organs.

Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

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.

Mercury species, selenium, metallothioneins and glutathione in two dolphins from the southeastern Brazilian coast: Mercury detoxification and physiological differences in diving capacity.

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.

Superoxide anion radical (O2(-)) degrades methylmercury to inorganic mercury in human astrocytoma cell line (CCF-STTG1).

Methylmercury (MeHg) is a global pollutant that is affecting the health of millions of people worldwide. However, the mechanism of MeHg toxicity still remains somewhat elusive and there is no treatment. It has been known for some time that MeHg can be progressively converted to inorganic mercury (iHg) in various tissues including the brain. Recent work has suggested that cleavage of the carbon-metal bond in MeHg in a biological environment is facilitated by reactive oxygen species (ROS). However, the oxyradical species that actually mediates this process has not been identified. Here, we provide evidence that superoxide anion radical (O2(-)) can convert MeHg to iHg. The calculated second-order rate constant for the degradation of 1µM MeHg by O2(-) generated by xanthine/xanthine oxidase was calculated to be 2×10(5)M(-1)s(-1). We were also able to show that this bioconversion can proceed in intact CCF-STTG1 human astrocytoma cells exposed to paraquat (PQ), a O2(-) generating viologen. Notably, exposure of cells to increasing amounts of PQ led to a dose dependent increase in both MeHg and iHg. Indeed, a 24h exposure to 500µM PQ induced a ∼13-fold and ∼18-fold increase in intracellular MeHg and iHg respectively. These effects were inhibited by superoxide dismutase mimetic MnTBAP. In addition, we also observed that a 24h exposure to a biologically relevant concentration of MeHg (1µM) did not induce cell death, oxidative stress, or even changes in cellular O2(-) and H2O2. However, co-exposure to PQ enhanced MeHg toxicity which was associated with a robust increase in cell death and oxidative stress. Collectively our results show that O2(-) can bioconvert MeHg to iHg in vitro and in intact cells exposed to conditions that simulate high intracellular O2(-) production. In addition, we show for the first time that O2(-) mediated degradation of MeHg to iHg enhances the toxicity of MeHg by facilitating an accumulation of both MeHg and iHg in the intracellular environment.

Methionine stimulates motor impairment and cerebellar mercury deposition in methylmercury-exposed mice.

Methylmercury (MeHg) is a highly toxic environmental contaminant that produces neurological and developmental impairments in animals and humans. Although its neurotoxic properties have been widely reported, the molecular mechanisms by which MeHg enters the cells and exerts toxicity are not yet completely understood. Taking into account that MeHg is found mostly bound to sulfhydryl-containing molecules such as cysteine in the environment and based on the fact that the MeHg-cysteine complex (MeHg-S-Cys) can be transported via the L-type neutral amino acid carrier transport (LAT) system, the potential beneficial effects of L-methionine (L-Met, a well known LAT substrate) against MeHg (administrated as MeHg-S-Cys)-induced neurotoxicity in mice were investigated. Mice were exposed to MeHg (daily subcutaneous injections of MeHg-S-Cys, 10 mg Hg/kg) and/or L-Met (daily intraperitoneal injections, 250 mg/kg) for 10 consecutive days. After treatments, the measured hallmarks of toxicity were mostly based on behavioral parameters related to motor performance, as well as biochemical parameters related to the cerebellar antioxidant glutathione (GSH) system. MeHg significantly decreased motor activity (open-field test) and impaired motor performance (rota-rod task) compared with controls, as well as producing disturbances in the cerebellar antioxidant GSH system. Interestingly, L-Met administration did not protect against MeHg-induced behavioral and cerebellar changes, but rather increased motor impairments in animals exposed to MeHg. In agreement with this observation, cerebellar levels of mercury (Hg) were higher in animals exposed to MeHg plus L-Met compared to those only exposed to MeHg. However, this event was not observed in kidney and liver. These results are the first to demonstrate that L-Met enhances cerebellar deposition of Hg in mice exposed to MeHg and that this higher deposition may be responsible for the greater motor impairment observed in mice simultaneously exposed to MeHg and L-Met.

Involvement of AAT transporters in methylmercury toxicity in Caenorhabditis elegans.

Methylmercury (MeHg) is a potent neurotoxin that enters mammalian cells as a conjugate with L-cysteine through L-type large neutral amino acid transporter, LAT1, by a molecular mimicry mechanism by structurally resembling L-methionine. Caenorhabditis elegans (C. elegans) has been increasingly used to study the neurotoxic effects of MeHg, but little is known about uptake and transport of MeHg in the worm. This study examined whether MeHg uptake through LAT1 is evolutionarily conserved in nematodes. MeHg toxicity in C. elegans was blocked by pre-treatment of worms with l-methionine, suggesting a role for amino acid transporters in MeHg transport. Knockdown of aat-1, aat-2, and aat-3, worm homologues to LAT1, increased the survival of C. elegans following MeHg treatment and significantly attenuated MeHg content following exposure. These results indicate that MeHg is transported in the worm by a conserved mechanism dependent on functioning amino acid transporters.

Selenoneine, a novel selenium-containing compound, mediates detoxification mechanisms against methylmercury accumulation and toxicity in zebrafish embryo.

The selenium (Se)-containing antioxidant selenoneine (2-selenyl-N α,N α,N α-trimethyl-L-histidine) has recently been discovered to be the predominant form of organic Se in tuna blood. Although dietary intake of fish Se has been suggested to reduce methylmercury (MeHg) toxicity, the molecular mechanism of MeHg detoxification by Se has not yet been determined. Here, we report evidence that selenoneine accelerates the excretion and demethylation of MeHg, mediated by a selenoneine-specific transporter, organic cations/carnitine transporter-1 (OCTN1). Selenoneine was incorporated into human embryonic kidney HEK293 cells transiently overexpressing OCTN1 and zebrafish blood cells by OCTN1. The K m for selenoneine uptake was 13.0 µM in OCTN1-overexpressing HEK293 cells and 9.5 µM in zebrafish blood cells, indicating high affinity of OCTN1 for selenoneine in human and zebrafish cells. When such OCTN1-expressing cells and embryos were exposed to MeHg-cysteine (MeHgCys), MeHg accumulation was decreased and the excretion and demethylation of MeHg were enhanced by selenoneine. In addition, exosomal secretion vesicles were detected in the culture water of embryos that had been microinjected with MeHgCys, suggesting that these may be responsible for MeHg excretion and demethylation. In contrast, OCTN1-deficient embryos accumulated MeHg, and MeHg excretion and demethylation were decreased. Furthermore, Hg accumulation was decreased in OCTN1-overexpressing HEK293 cells, but not in mock vector-transfected cells, indicating that selenoneine and OCTN1 can regulate MeHg detoxification in human cells. Thus, the selenoneine-mediated OCTN1 system regulates secretory lysosomal vesicle formation and MeHg demethylation.

Mercury elimination by a top predator, Esox lucius.

Top-level piscivores are highly sought after for consumption in freshwater fisheries, yet these species contain the highest levels of the neurotoxin monomethylmercury (MMHg) and therefore present the greatest concern for MMHg exposure to humans. The slow elimination of MMHg is one factor that contributes to high levels of this contaminant in fish; however, little quantitative information exists on elimination rates by top predators in nature. We determined rates of MMHg elimination in northern pike (Esox lucius) by transferring fish that had naturally accumulated isotope-enriched MMHg (spike MMHg) through a whole-lake Hg loading study to a different lake. Over a period of ~7 y, pike were periodically recaptured and a small amount of muscle tissue was extracted using a nonlethal biopsy. Spike total mercury (THg) persisted in muscle tissue throughout the entire study despite discontinuing exposure upon transfer to the new lake. Spike THg burdens increased for the first ~460 d, followed by a decline to 65% of original burden levels over the next 200 d, and subsequently reached a plateau near original burden levels for the remainder of the study. We estimated the half-life of muscle THg to be 3.3 y (1193 d), roughly 1.2- to 2.7-fold slower than predicted by current elimination models. We advocate for further long-term field studies that examine kinetics of MMHg in fish to better inform predictive models estimating the recovery of MMHg-contaminated fisheries.

Comparison of in vivo with in vitro pharmacokinetics of mercury between methylmercury chloride and methylmercury cysteine using rats and Caco2 cells.

The in vivo and in vitro pharmacokinetics of mercury (Hg) were compared between methylmercury chloride (MeHg·Cl) and methylmercury cysteine (MeHg-Cys) using rats and Caco2 cells because humans can be exposed to MeHg compounds through dietary fish. The in vivo pharmacokinetics of Hg immediately after the digestion of MeHg compounds are still obscure. In Caco2 cells, membrane uptake and subcellular distribution of MeHg compounds were examined. When rats received it intravenously, MeHg·Cl showed 20-fold greater plasma and 2-fold greater blood concentrations of Hg than MeHg-Cys, indicating that their pharmacokinetic properties are different. One hour later, however, Hg concentrations in plasma and blood became virtually identical between MeHg·Cl and MeHg-Cys, although blood Hg concentrations were >100-fold greater than those in plasma. When administered into the closed rat's jejunum loop, MeHg·Cl and MeHg-Cys were rapidly and efficiently taken up by intestinal membranes, and Hg was retained in intestinal membranes for a relatively long time. When administered orally, no difference was observed in plasma and blood Hg concentrations between MeHg·Cl and MeHg-Cys: plasma and blood Hg concentrations increased gradually and reached steady levels at 8 h after administration. In Caco2 cells, uptake of MeHg-Cys was significantly suppressed by L-leucine, although this was not seen with MeHg·Cl. In Caco2 cells, 81 % of Hg was recovered from cytosol fractions and 13 % of Hg from nuclear fractions (including debris) after a 2-h incubation with MeHg-Cys. In conclusion, the mechanism of membrane uptake and volume of distribution in the initial distribution phase were clearly different between MeHg·Cl and MeHg-Cys. However, such pharmacokinetic differences between them disappeared 1 h after intravenous and after oral routes of administration, possibly due to the metabolism in the body.

Effect of inorganic and organic ligands on the bioavailability of methylmercury as determined by using a mer-lux bioreporter.

A mer-lux bioreporter was constructed to assess the bioavailability of methylmercury [CH(3)Hg(II)] in Escherichia coli. The bioreporter was shown to be sensitive, with a detection limit of 2.5 nM CH(3)Hg(II), and was used to investigate the effects of chlorides, humic acids, and thiols on the bioavailability of CH(3)Hg(II) in E. coli. It was found that increasing the concentration of chlorides resulted in an increase in CH(3)Hg(II) bioavailability, suggesting that there was passive diffusion of the neutral complex (CH(3)HgCl(0)). Humic acids were found to reduce the bioavailability of CH(3)Hg(II) in varying degrees. Complexation with cysteine resulted in increased bioavailability of CH(3)Hg(II), while assays with equivalent concentrations of methionine and leucine had little or no effect on bioavailability. The mechanism of uptake of the mercurial-cysteine complexes is likely not passive diffusion but could result from the activities of a cysteine transport system. The bioavailability of CH(3)Hg(II) decreased with increasing glutathione concentrations.

Luminal transport of thiol S-conjugates of methylmercury in isolated perfused rabbit renal proximal tubules.

Lumen-to-cell transport, cellular accumulation, and toxicity of L-cysteine (Cys), glutathione (GSH) and N-acetylcysteine (NAC) S-conjugates of methylmercury (CH(3)Hg(+)) were evaluated in isolated, perfused rabbit proximal tubular segments. When these conjugates were perfused individually through the lumen of S(2) segments of the proximal tubule it was found that Cys-S-CH(3)Hg and GSH-S-CH(3)Hg were transported avidly, while NAC-S-CH(3)Hg was transported minimally. In addition, 95% of the (203)Hg taken up by the tubular cells was associated with precipitable proteins of the tubule, while very little was found in the acid-soluble cytosol. No visual cellular pathological changes were observed during 30min of study. Luminal uptake of Cys-S-CH(3)Hg was temperature-dependent and inhibited significantly by the amino acids L-methionine and l-cystine. Rates of luminal uptake of GSH-S-CH(3)Hg were twice as great as that of Cys-S-CH(3)Hg and uptake was inhibited significantly (74%) by the presence of acivicin. When 2,3-bis(sulfanyl)propane-1-sulfonate (DMPS) was added to the bathing or luminal fluid, luminal uptake of Cys-S-CH(3)Hg was diminished significantly. Overall, our data indicate that Cys-S-CH(3)Hg is likely a transportable substrate of one or more amino acid transporters (such as system B(0,+) and system b(0,+)) involved in luminal absorption of L-methionine and L-cystine along the renal proximal tubule. In addition, GSH-S-CH(3)Hg appears to be degraded enzymatically to Cys-S-CH(3)Hg, which can then be taken up at the luminal membrane. By contrast NAC-S-CH(3)Hg and Cys-S-CH(3)Hg (in the presence of DMPS) are not taken up avidly at the luminal membrane of proximal tubular cells, thus promoting the excretion of CH(3)Hg(+) into the urine.

Dissolved organic matter reduces algal accumulation of methylmercury.

Dissolved organic matter (DOM) significantly decreased accumulation of methylmercury (MeHg) by the diatom Cyclotella meneghiniana in laboratory experiments. Live diatom cells accumulated two to four times more MeHg than dead cells, indicating that accumulation may be partially an energy-requiring process. Methylmercury enrichment in diatoms relative to ambient water was measured by a volume concentration factor (VCF). Without added DOM, the maximum VCF was 32 × 10(4) , and the average VCF (from 10 to 72 h) over all experiments was 12.6 × 10(4) . At very low (1.5 mg/L) added DOM, VCFs dropped by approximately half. At very high (20 mg/L) added DOM, VCFs dropped 10-fold. Presumably, MeHg was bound to a variety of reduced sulfur sites on the DOM, making it unavailable for uptake. Diatoms accumulated significantly more MeHg when exposed to transphilic DOM extracts than hydrophobic ones. However, algal lysate, a labile type of DOM created by resuspending a marine diatom in freshwater, behaved similarly to a refractory DOM isolate from San Francisco Bay. Addition of 67 µM L-cysteine resulted in the largest drop in VCFs, to 0.28 × 10(4) . Although the DOM composition influenced the availability of MeHg to some extent, total DOM concentration was the most important factor in determining algal bioaccumulation of MeHg.

Chronic methyl mercury poisoning may trigger endemic pemphigus foliaceus "fogo selvagem".

In endemic pemphigus foliaceus (EPF) or "fogo selvagem" the epidemiological evidence shows that all the described outbreaks occur on the banks of rivers where there is mercury contamination from alluvium gold mining and deforestation. Pathophysiological evidence shows a similarity to pemphigus induced by sulphydryl (SH-) drugs that act by denaturing cadherins at the desmosomal level, which are the pemphigus antigens. The sulfhydryl radical (SH-) call also thiol or mercaptans from the SH-drugs, act at the level of SH-groups of cystein as would the methyl mercury from the contaminated animals and fish in the diet of humans from endemic areas of pemphigus foliaceus. The methyl mercury would join the SH-groups from the cysteines amino acids from cadherin proteins in the skin. The autoimmune disease would only be triggered in genetically susceptible individuals with human leukocyte antigen HLA-DRB 1 haplotypes, just as Brown-Norway (BN) rats which are susceptible to develop Th2-dependent autoimmunity induced by metals. Immunological evidence from all the seroepidemiological studies could also be explained by binding mechanism of the methyl mercury to the SH-groups from the cysteines in the desmosomal cadherins proteins. The conclusion is that chronic methyl mercury poisoning is the most likely trigger of endemic pemphigus foliaceus "fogo selvagem". To reduce the contamination of methyl mercury in the animals of the polluted rivers is pertinent to the design of campaigns and education programs with the population. Implement reforestation and biological control measures like phytoremediation technologies using decontaminant plants to decrease the methylation, and the process of biomagnifications of the methyl mercury in the Latin-America EPF foci.

Therapeutic potential of N-acetyl cysteine with antioxidants (Zn and Se) supplementation against dimethylmercury toxicity in male albino rats.

Mercury (Hg) is currently one of the most prevalent pollutants in the environment. Many studies have examined its effects on the health of both humans and animals. Experimental studies have shown that sulfur-containing nutrients play an important role as detoxification and protecting cell against the detrimental properties of mercury. The present study was undertaken to elucidate the toxicity induced by dimethylmercury in male rats through the activities of transaminases, alkaline phosphatase, lactate dehydrogenase in serum and oxidative damage as acetyl cholinesterase activity in different regions of brain and lipid peroxidation, reduced glutathione content, mean DNA damage in liver, kidney and brain of rats given dimethylmercury (10 mg/kg, p.o., once only) along with combination therapy of N-acetyl cysteine (2 mM/kg, i.p.), zinc (2 mM/kg, p.o.) and selenium (0.5 mg/kg, p.o.) for 3 days. In the dimethylmercury group, activities of transaminases, alkaline phosphatase, lactate dehydrogenase in serum, level of lipid peroxidation, mean DNA damage and mercury ion concentration were significantly higher whereas reduced glutathione content and the activity of acetyl cholinesterase were significantly lower compared to controls (P≤0.05). Combined treatment of zinc and selenium with N-acetyl cysteine to dimethylmercury-exposed rats showed a substantial reduction in the levels of DMM-induced oxidative damage and comet tail length. In conclusion, the results of this study support that the supplementation of zinc and selenium with N-acetyl cysteine can improve the DMM induced blood and tissue biochemical oxidative stress and molecular alterations by recoupment in mean DNA damage.