Methylmercury-induced hair cell loss requires hydrogen peroxide production and leukocytes in zebrafish embryos.

Hearing impairment and deafness is frequently observed as one of the neurological signs in patients with Minamata disease caused by methylmercury (MeHg) poisoning. Loss of hair cells in humans and animals is a consequence of MeHg poisoning. However, it is still not clear how MeHg causes hearing deficits. We employed the hair cells of the lateral line system of zebrafish embryos as a model to explore this question. We exposed transgenic zebrafish embryos to MeHg (30-360 µg/L) at the different stages, and scored the numbers of hair cells. We find that MeHg-induced reduction of hair cells is in a concentration dependent manner. By employing antisense morpholino against to pu.1, we confirm that loss of hair cells involves the action of leukocytes. Moreover, hair cell loss is attenuated by co-treating MeHg-exposed embryos with pharmacological inhibitors of NADPH oxidases named diphenyleneiodonium (DPI) and VAS2870. In situ gene expression analysis showed that genes encoding the SQSTM1-Keap1-Nrf2 systems involved in combating oxidative stress and immune responses are highly expressed in the lateral line organs of embryos exposed to MeHg. This suggests that induction of hydrogen peroxide (H2O2) is the primary effect of MeHg on the hair cells. Genes induced by MeHg are also involved in regeneration of the hair cells. These features are likely related to the capacity of the zebrafish to regenerate the lost hair cells.

Hypoalgesia and recovery in methylmercury-exposed rats.

Methylmercury (MeHg), the causal substrate in Minamata disease, can lead to severe and chronic neurological disorders. The main symptom of Minamata disease is sensory impairment in the four extremities; however, the sensitivity of individual sensory modalities to MeHg has not been investigated extensively. In the present study, we performed stimulus-response behavioral experiments in MeHg-exposed rats to compare the sensitivities to pain, heat, cold, and mechanical sensations. MeHg (6.7 mg/kg/day) was orally administered to 9-week-old Wistar rats for 5 days and discontinued for 2 days, then administered daily for another 5 days. The four behavioral experiments were performed daily on each rat from the beginning of MeHg treatment for 68 days. The pain sensation decreased significantly from day 11 onwards, but recovered to control levels on day 48. Other sensory modalities were not affected by MeHg exposure. These findings suggest that the pain sensation is the sensory modality most susceptive to MeHg toxicity and that this sensitivity is reversible following discontinuation of the exposure.

Methylmercury induces neuronal cell death by inducing TNF-α expression through the ASK1/p38 signaling pathway in microglia.

We recently found that tumor necrosis factor-α (TNF-α) may be involved in neuronal cell death induced by methylmercury in the mouse brain. Here, we examined the cells involved in the induction of TNF-α expression by methylmercury in the mouse brain by in situ hybridization. TNF-α-expressing cells were found throughout the brain and were identified as microglia by immunostaining for ionized calcium binding adaptor molecule 1 (Iba1). Methylmercury induced TNF-α expression in mouse primary microglia and mouse microglial cell line BV2. Knockdown of apoptosis signal-regulating kinase 1 (ASK1), an inflammatory cytokine up-regulator that is responsible for reactive oxygen species (ROS), decreased methylmercury-induced TNF-α expression through decreased phosphorylation of p38 MAP kinase in BV2 cells. Suppression of methylmercury-induced reactive oxygen species (ROS) by antioxidant treatment largely abolished the induction of TNF-α expression and phosphorylation of p38 by methylmercury in BV2 cells. Finally, in mouse brain slices, the TNF-α antagonist (WP9QY) inhibited neuronal cell death induced by methylmercury, as did the p38 inhibitor SB203580 and liposomal clodronate (a microglia-depleting agent). These results indicate that methylmercury induces mitochondrial ROS that are involved in activation of the ASK1/p38 pathway in microglia and that this is associated with induction of TNF-α expression and neuronal cell death.

Ecotoxicity Risk of Low-Dose Methylmercury Exposure to Caenorhabditis elegans: Multigenerational Toxicity and Population Discrepancy.

Methylmercury (MeHg) is a common organic form of mercury in water, which has been linked to several forms of biological toxicity. However, studies on the ecotoxicity risk of long-term exposure to low-dose MeHg are insufficient for the assessment of environmental safety. In the present study, the effects of MeHg on multiple generations (P0-F3) and population of Caenorhabditis elegans were investigated under long-term, low-dose exposure. We investigated the multigenerational toxicity of MeHg by analyzing reproductive and developmental indicators. According to our results, exposure to 100 nM MeHg had little effect on the parental generation (P0) but caused serious reproductive toxicity in the offspring (F1-F3), and the effect of MeHg was aggravated with each passing generation. The genes related to apoptosis and DNA damage were upregulated in the F3 generation. Pearson correlation analysis showed that the changes in these genes were closely related to the apoptosis of gonadal cells. Furthermore, chronic exposure to MeHg (from 100 to 1000 nM group) caused a sharp decline in population size and triggered the "bag of worms" phenotype. Genes related to vulvar development were downregulated in the F3 generation after treatment with 100 nM MeHg. These data suggest that long-term low-dose MeHg exposure adversely affected C. elegans and its offspring and triggered multigenerational toxicity and population discrepancy.

Latent alterations in swimming behavior by developmental methylmercury exposure are modulated by the homolog of tyrosine hydroxylase in Caenorhabditis elegans.

Methylmercury (MeHg) is a persistent environmental neurotoxicant that may cause adverse neurodevelopmental effects. Previous studies showed that developmental MeHg exposure caused damage to brain functions that were unmasked after a silent period of years or decades. However, the underlying mechanisms of the latent neurotoxicity associated with MeHg exposure from earlier developmental stages have yet to be fully understood. Herein, we established a Caenorhabditis elegans (C. elegans) model of developmental MeHg latent toxicity. Synchronized L1 stage worms were exposed to MeHg (0, 0.05, 0.5 and 5 µM) for 48 h. Swimming moving speeds at adulthood were analyzed in worms exposed to MeHg exposure at early larvae stages. Worms developmentally exposed to MeHg had a significant decline in swimming moving speed on day 10 adult stage, but not on day 1 or 5 adult stage, even though the mercury level in the worms exposed to 0.05 or 0.5 µM MeHg were below the quantification limit on day 10 adult. Day 10 adult worms treated with MeHg showed a significant decrease in bending angle and bending frequency during swimming. Furthermore, their reduced moving speeds tended to increase during the 300-s swimming experiment. Dopamine signaling is known to be involved in the regulation of worms' moving speed. Accordingly, the moving speed of worms with cat-2 (mammalian tyrosine hydroxylase homolog) mutation or dat-1 deletion were assayed on day 10 adult. The cat-2 mutant worms did not show a decline in moving speeds, body bends or bending angles during swimming on day 10 adult stage. Analyses of moving speeds of worms with dat-1 deletion showed that the moving speeds were further reduced after MeHg exposure. However, the effects of MeHg and dat-1 deletion were not synergistic, as the interaction between these parameters did not attain statistical significance. Altogether, our results suggest that developmental MeHg exposure reduced moving speed, and this latent toxicity was less pronounced in the context of deficient production of dopamine synthesis. Tyrosine hydroxylase plays an important role in regulating dopamine-mediated modulation of neurobehavioral functions. These findings uncovered a pivotal role of dopamine and its metabolism in the latent neurotoxic effects of MeHg.

The burden of disease of three food-associated heavy metals in clusters in the Danish population - Towards targeted public health strategies.

Lifestyle and sociodemographics are likely to influence dietary patterns, and, as a result, human exposure to chemical contaminants in foods and their associated health impact. We aimed to characterize subgroups of the Danish population based on diet and sociodemographic indicators, and identify those bearing a higher disease burden due to exposure to methylmercury (MeHg), cadmium (Cd) and inorganic arsenic (i-As). We collected dietary, lifestyle, and sociodemographic data on the occurrence of chemical contaminants in foods from Danish surveys. We grouped participants according to similarities in diet, lifestyle, and sociodemographics using Self-Organizing Maps (SOM), and estimated disease burden in disability-adjusted life years (DALY). SOM clustering resulted in 12 population groups with distinct characteristics. Exposure to contaminants varied between clusters and was largely driven by intake of fish, seafood and cereal products. Five clusters had an estimated annual burden >20 DALY/100,000. The cluster with the highest burden had a high proportion of women of childbearing age, with most of the burden attributed to MeHg. Individuals belonging to the top three clusters had higher education and physical activity, were mainly non-smokers and lived in urban areas. Our findings may facilitate the development of preventive strategies targeted to the most affected subgroups.

DNA methyltransferase- and histone deacetylase-mediated epigenetic alterations induced by low-level methylmercury exposure disrupt neuronal development.

Methylmercury (MeHg) is a chemical substance that causes adverse effects on fetal development. However, the molecular mechanisms by which environmental MeHg affects fetal development have not been clarified. Recently, it has been suggested that the toxic effects of chemicals on fetal development are related alterations in epigenetics, such as DNA methylation and histone modification. In order to analyze the epigenetic effects of low-level MeHg exposure on neuronal development, we evaluated neuronal development both in vivo and in vitro. Pregnant mice (C57BL/6J) were orally administrated 3 mg/kg of MeHg once daily from embryonic day 12-14. Fetuses were removed on embryonic day 19 and brain tissues were collected. LUHMES cells were treated with 1 nM of MeHg for 6 days and collected on the last day of treatment. In both in vivo and in vitro samples, MeHg significantly suppressed neurite outgrowth. Decreased acetylated histone H3 (AcH3) levels and increased histone deacetylase (HDAC) 3 and HDAC6 levels were observed in response to MeHg treatment in both in vivo and in vitro experiments. In addition, increased DNA methylation and DNA methyltransferase 1 (DNMT1) levels were observed in both in vivo and in vitro experiments. The inhibition of neurite outgrowth resulting from MeHg exposure was restored by co-treatment with DNMT inhibitor or HDAC inhibitors. Our results suggest that neurological effects such as reduced neurite outgrowth due to low-level MeHg exposure result from epigenetic changes, including a decrease in AcH3 via increased HDAC levels and an increase in DNA methylation via increased DNMT1 levels.

Exposure assessment of methylmercury in samples of the BfR MEAL Study.

The BfR MEAL Study is the first German total diet study and will establish a representative and comprehensive database for dietary exposure assessment in Germany. The present study reports first results of the BfR MEAL Study regarding methylmercury in fish, seafood and mushrooms. In total, 34 MEAL foods were purchased nationally or regionally according to a defined sampling plan, prepared in a representative way for German households, pooled into 49 samples, homogenized and subjected to ICP-MS analysis. Dogfish, tuna, ocean perch, halibut and eel were the fish species with highest MeHg concentrations, while levels in mushrooms and mushroom products had markedly lower MeHg levels. Exposure was estimated by matching the present results with consumption data at appropriate levels of food group aggregation. MeHg exposure for adult high consumers (P 95) exceeded the tolerable weekly intake recommended by the European Food Safety Authority in two age groups (14-17 and 18-24 years). In children, no age group exceeded the recommended tolerable weekly intake. Regional samples differed only slightly in MeHg levels. The differences in exposure found in four regions of Germany were influenced by consumption habits rather than MeHg level in the investigated food.

Chronic exposure to methylmercury enhances the anorexigenic effects of leptin in C57BL/6J male mice.

Several studies have demonstrated that heavy metals disrupt energy homeostasis. Leptin inhibits food intake and decreases body weight through activation of its receptor in the hypothalamus. The impact of heavy metals on leptin signaling in the hypothalamus is unclear. Here, we show that the environmental pollutant, methylmercury (MeHg), favors an anorexigenic profile in wild-type males. C57BL/6J mice were exposed to MeHg via drinking water (5 ppm) up to 30 days. Our data shows that MeHg exposure was associated with changes in leptin induced activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in the hypothalamus. In males, the activation of JAK2/STAT3 signaling pathway was sustained by an increase in SOCS3 protein levels. In females, MeHg-activated STAT3 was inhibited by a concomitant increase in PTP1B. Taken together, our data suggest that MeHg enhanced leptin effects in males, favoring an anorexigenic profile in males, which notably, have been shown to be more sensitive to the neurological effects of this organometal than females. A better understanding of MeHg-induced molecular mechanism alterations in the hypothalamus advances the understanding of its neurotoxicity and provides molecular sites for novel therapies.

Effects of foetal and breastfeeding exposure to methylmercury (MeHg) and retinol palmitate (Vitamin A) in rats: Redox parameters and susceptibility to DNA damage in liver.

Methylmercury (MeHg) is known to be a chemical that poses a risk to public health. Exposure to MeHg and vitamin A (VitA) occurs through the ingestion of fish, present in the diet of most pregnant women. The absorption of these elements generates oxidative stress and can generate adaptations for future stressful events. Here, we assessed how exposure to VitA and/or MeHg during the fetal and breastfeeding period modulates the toxicity of MeHg reexposure in adulthood. We focus on redox systems and repairing DNA damage. Male rats (n = 50), were divided into 5 groups. Control received mineral oil; The VitA group received VitA during pregnancy, during breastfeeding and was exposed to MeHg in adulthood; VitA + MeHg received VitA and MeHg during pregnancy and breastfeeding and was exposed to MeHg in adulthood. The single exposure group (SE) was exposed to MeHg only in adulthood; and the MeHg group was pre-exposed to MeHg during pregnancy and breastfeeding and re-exposed to MeHg in adulthood. After treating the animals, we evaluated the redox status and the level of DNA damage in all rats. The results revealed that MeHg significantly decreased the activity of glutathione peroxidase (GPx) and sulfhydryl levels and increased the activity of superoxide dismutase (SOD), glutathione transferase, glutathione and carbonyl in all exposed groups. These results suggest that the second exposure to MeHg directly altered the effects of oxidation and that there were no specific effects associated with exposure during the fetal and breastfeeding periods. In addition, our findings indicate that MDA levels increased in MeHg and SE levels and no differences in MDA levels were observed between the VitA and MeHg + VitA groups. We also observed that animals pretreated exclusively with VitA showed residual damage similar to the control's DNA, while the other groups showed statistically higher levels of damage. In conclusion, low doses of MeHg and VitA during fetal and breastfeeding periods were unable to condition an adaptive response to subsequent exposure to MeHg in adulthood in relation to the observed levels of oxidative damage assessed after exposure.

Uptake, efflux, and toxicity of inorganic and methyl mercury in the endothelial cells (EA.hy926).

Cardiovascular disease (CVD) is the major cause of morbidity, mortality, and health care costs in the United States, and possibly around the world. Among the various risk factors of CVD, environmental and dietary exposures to mercury (Hg), a highly toxic metal traditionally regarded as a neurotoxin, has been recently suggested as a potential contributor towards human atherosclerotic development. In this study, we investigated the toxicity, type of cell death, dose-dependent uptake, and efflux of inorganic HgII (as HgCl2) and methylmercury or MeHg (as CH3HgCl) in EA.hy926 endothelial cells, as these two forms of Hg are often reported to be present in human blood among the general populations (~20-30% as HgII and ~70-80% as MeHg). Our results showed that HgII is more toxic than MeHg to the endothelial cells, owing to the higher uptake into the cytoplasm and perhaps importantly lower efflux of HgII by the cells, thus the "net" accumulation by the endothelial cells is higher for HgII than MeHg when exposed to the same Hg levels in the media. Furthermore, both HgII and MeHg were found to induce apoptotic and necrotic cell death. This study has important implications for the contributions of these two common Hg species to the development of atherosclerosis, an important process leading to CVD.

Niacin prevents mitochondrial oxidative stress caused by sub-chronic exposure to methylmercury.

Humans and animals can be exposed to different chemical forms of mercury (Hg) in the environment. For example, methylmercury (MeHg)-contaminated fish is part of the basic diet of the riparian population in the Brazilian Amazon Basin, which leads to high total blood and plasma Hg levels in people living therein. Hg induces toxic effects mainly through oxidative stress. Different compounds have been used to prevent the damage caused by MeHg-induced reactive oxygen species (ROS). This study aims to investigate the in vivo effects of sub-chronic exposure to low MeHg levels on the mitochondrial oxidative status and to evaluate the niacin protective effect against MeHg-induced oxidative stress. For this purpose, Male Wistar rats were divided into four groups: control group, treated with drinking water on a daily basis; group exposed to MeHg at a dose of 100 µg/kg/day; group that received niacin at a dose of 50 mg/kg/day in drinking water, with drinking water being administered by gavage; group that received niacin at a dose of 50 mg/kg/day in drinking water as well as MeHg at a dose of 100 µg/kg/day. After 12 weeks, the rats, which weighed 500-550 g, were sacrificed, and their liver mitochondria were isolated by standard differential centrifugation. Sub-chronic exposure to MeHg (100 µg/kg/day for 12 weeks) led to mitochondrial swelling (p < 0.05) and induced ROS overproduction as determined by increased DFCH oxidation (p < 0.05), increased gluthatione oxidation (p < 0.05), and reduced protein thiol content (p < 0.05). In contrast, niacin supplementation inhibited oxidative stress, which counteracted and minimized the toxic MeHg effects on mitochondria.

Simultaneous exposure to vinylcyclohexene and methylmercury in Drosophila melanogaster: biochemical and molecular analyses.

BACKGROUND: Exposure to vinylcyclohexene (VCH) and methylmercury (MeHg+) can induce oxidative stress and gene modulation. Several studies have been evaluating the effects of VCH and MeHg+, but little is known about interactive effects between them. This work aimed to assess the exposure and co-exposure effects of MeHg+ and VCH on oxidative stress and gene modulation in Drosophila melanogaster. METHODS: Reactive species production, glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities were evaluated after exposure and co-exposure to VCH (1 mM) and MeHg+ (0.2 mM) for one or three days in the head and body (thorax and abdomen) of flies. The expression of genes related to redox state and inflammatory response was evaluated after exposure and co-exposure to VCH and MeHg+ for three days. RESULTS: Survival decreased only in flies co-exposed to VCH and MeHg+ for three days. All treatments increased total reactive species production after one day of exposure. However, no significant changes were observed in the head after three days of exposure. One day of exposure to VCH caused an increase in the head GST activity, whereas MeHg+ induced an increase after three days of exposure. Regarding the body, all treatments increased GST activity after one day of exposure, but only the flies exposed to MeHg+ presented an increase in GST activity after three days of exposure. Treatments did not alter AChE activity in the head. As for gene expression, there was a significant increase in the Relish transcription factor gene in the flies' body, but Nrf2, Keap1, Jafrac1, TrxR1, and NF-κß were not altered. CONCLUSION: The results suggest that exposure to VCH and MeHg+ induce oxidative stress and activation of an inflammatory response in fruit flies.

Risk assessment of methylmercury in pregnant women and newborns in the island of Madeira (Portugal) using exposure biomarkers and food-frequency questionnaires.

Methylmercury (MeHg) is a contaminant present in fish which exerts a severe impact on health predominantly exhibiting neurotoxicity that might irreversibly affect fetal neurodevelopment. Fish consumption in Portugal is the third highest in the world, particularly high in regions with fishing tradition such as the Madeira Archipelago. Therefore, this study aimed at assessing the risk of exposure to MeHg in a population of pregnant women residing in Madeira. Blood samples from pregnant women (533) and umbilical cord (194) were collected from volunteer participants collected at primary health services in Madeira (Portugal) and analyzed for total mercury (HgT) level. A food-frequency questionnaire was used to estimate exposure and indices of risk while HgT in blood were correlated with estimated exposure. Analysis of HgT levels in blood indicated that 30% of pregnant women surpassed the maximum safe level of 10 µg/L recommended by the WHO, which was derived from the consumption of predatory fish, rich in MeHg. In addition, HgT levels in cord blood were 1.3 fold higher than in maternal blood, indicating the high risk of exposure to MeHg in this population. It is thus important to provide nutritional advice concerning fish consumption as a food choice in order to reduce fetal exposure and potential neurologic damage.

Gene expression profiles in the dorsal root ganglia of methylmercury-exposed rats.

Methylmercury (MeHg) exposure is known to induce neurodegeneration in both the central nervous system (CNS) and peripheral nervous system (PNS). Molecular mechanisms of MeHg-induced neurotoxicity have been well investigated in the CNS, however, it remains unclear in the PNS. In the present study, comprehensive gene expression analysis was performed by analyzing MeHg-exposed adult rat dorsal root ganglion (DRG) by DNA microarray. Methylmercuric chloride (6.7 mg/kg/day) was administered to nine-week-old male Wistar rats for five days, followed by two days without administration; this cycle was repeated once. Rats were anesthetized at 7 or 14 days after commencement of MeHg exposure, and their DRGs were removed and homogenized to make total RNA samples. DNA microarray data from Day 7 samples identified 100 out of 18,513 detected genes as annotated genes with more than two-fold upregulated or downregulated expression compared with controls. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested strong involvement of immune activation and inflammation pathways in rat DRG exposed to MeHg, and some genes overlapped with previously reported genes affected by MeHg exposure in the cerebellum. The present results suggest that MeHg-induced neurotoxicity is associated with immune activation and inflammatory responses in rat DRG.

Neurodevelopmental and Metabolomic Responses from Prenatal Coexposure to Perfluorooctanesulfonate (PFOS) and Methylmercury (MeHg) in Sprague-Dawley Rats.

Methylmercury (MeHg) and perfluorooctanesulfonate (PFOS) are major contaminants of human blood that are both common in dietary fish, thereby raising questions about their combined impact on human development. Here, pregnant Sprague-Dawley rats ingested a daily dose, from gestational day 1 through to weaning, of either 1 mg/kg bw PFOS (PFOS-only), 1 mg/kg MeHg (MeHg-only), a mixture of 0.1 mg/kg PFOS and 1 mg/kg MeHg (Low-Mix), or of 1 mg/kg of PFOS and 1 mg/kg MeHg (High-Mix). Newborns were monitored for physical milestones and reflexive developmental responses, and in juveniles the spontaneous activity, anxiety, memory, and cognition were assessed. Targeted metabolomics of 199 analytes was applied to sectioned brain regions of juvenile offspring. Newborns in the High-Mix group had decreased weight gain as well as delayed reflexes and innate behavioral responses compared to controls and individual chemical groups indicating a toxicological interaction on early development. In juveniles, cumulative mixture effects increased in a dose-dependent manner in tests of anxiety-like behavior. However, other developmental test results suggested antagonism, as PFOS-only and MeHg-only juveniles had increased hyperactivity and thigmotaxic behavior, respectively, but fewer effects in Low-Mix and High-Mix groups. Consistent with these behavioral observations, a pattern of antagonism was also observed in neurochemicals measured in rat cortex, as PFOS-only and MeHg-only juveniles had altered concentrations of metabolites (e.g., lipids, amino acids, and biogenic amines), while no changes were evident in the combined exposures. The cortical metabolites altered in PFOS-only and MeHg-only exposed groups are involved in inhibitory and excitatory neurotransmission. These proof-of-principle findings at relatively high doses indicate the potential for toxicological interaction between PFOS and MeHg, with developmental-stage specific effects. Future mixture studies at lower doses are warranted, and prospective human birth cohorts should consider possible confounding effects from PFOS and mercury exposure on neurodevelopment.

Biochemical evidence on the potential role of methyl mercury in hepatic glucose metabolism through inflammatory signaling and free radical pathways.

Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6-phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators' cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8-deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals.

Awareness of Listeriosis and Methylmercury toxicity public health recommendations and diet during pregnancy.

BACKGROUND: Awareness of Listeriosis and Methylmercury toxicity recommendations are associated with decreased intake of high-risk foods. Whether awareness of the recommendations affect dietary quality of pregnant women in Australian is unknown. AIM: To evaluate awareness of Listeriosis and Methylmercury toxicity recommendations during pregnancy and its impact on dietary quality. METHODS: Pregnant women (n=81) were recruited from antenatal clinics. Awareness of Listeriosis and Methylmercury toxicity recommendations and high-risk foods consumption were assessed via questionnaire at 10-23 weeks gestation. Diet quality was measured using the 2005 Healthy Eating Index using a validated food frequency questionnaire at 10-23 and 34-36 weeks gestation. FINDINGS: A higher proportion of women were aware of Methylmercury toxicity compared with Listeriosis recommendations (75.3 vs. 59.2%, p<0.001). The proportion of women who decreased or avoided consumption of certain high-risk Listeriosis foods were higher in those who were aware compared with those who were unaware of Listeriosis recommendations [raw fish (96.0 vs 69.2%, p=0.046), soft-serve ice cream (93.9 vs 58.3%, p=0.004) and alfalfa/bean sprouts (68.7 vs 28.5%, p=0.006)]. A large proportion of women (96.8%) met recommendations for limiting consumption of high Methylmercury fish. There was no difference in the change in dietary quality over pregnancy regardless of women's awareness of the recommendations. DISCUSSION AND CONCLUSIONS: Awareness of Listeriosis and Methylmercury toxicity recommendations has little impact on dietary quality of pregnant women in this small study. Further research in a large representative population of pregnant women is needed to confirm our findings and to optimise dietary quality during pregnancy.

Low doses of methylmercury exposure during adulthood in rats display oxidative stress, neurodegeneration in the motor cortex and lead to impairment of motor skills.

Despite the vast distribution among tissues, the central nervous system (CNS) represents the main target of methylmercury (MeHg) toxicity. However, few studies have evaluated the effects of MeHg exposure on the CNS at equivalent doses to human environmental exposure. In our study, we evaluated the motor cortex, an important area of motor control, in adult rats chronically exposed to MeHg in a concentration equivalent to those found in fish-eating populations exposed to mercury (Hg). The parameters evaluated were total Hg accumulation, oxidative stress, tissue damage, and behavioral assessment in functional actions that involved this cortical region. Our results show in exposed animals a significantly greater level of Hg in the motor cortex; increase of nitrite levels and lipid peroxidation, associated with decreased antioxidant capacity against peroxyl radicals; reduction of neuronal and astrocyte density; and poor coordination and motor learning impairment. Our data showed that chronic exposure at low doses to MeHg is capable of promoting damages to the motor cortex of adult animals, with changes in oxidative biochemistry misbalance, neurodegeneration, and motor function impairment.

Neurobehavioral and oxidative stress alterations following methylmercury and retinyl palmitate co-administration in pregnant and lactating rats and their offspring.

Fish consumption and ubiquitous methylmercury (MeHg) exposure represent a public health problem globally. Micronutrients presented in fish affects MeHg uptake/distribution. Vitamin A (VitA), another fish micronutrient is used in nutritional supplementation, especially during pregnancy. However, there is no information about the health effects arising from their combined exposure. The present study aimed to examine the effects of both MeHg and retinyl palmitate administered to pregnant and lactating rats. Thirty Wistar female rats were orally supplemented with MeHg (0,5 mg/Kg/day) and retinyl palmitate (7500 µg RAE1/Kg/day), either individually or in combination from the gestational day 0 to weaning. In dams, maternal behavior was scored. In neonatal and infant offspring, associative learning and neurodevelopment were evaluated. Further periadolescent male and female pups were assessed for open field, habituation and object recognition using episodic-like memory paradigm. Maternal and offspring redox parameters were evaluated. Our results showed no effects of MeHg-VitA co-administration in the quality of maternal care but showed subtle alterations in the pro-oxidant response of the hippocampus. In offspring, MeHg-VitA co-exposure affected early associative learning in neonatal pups, with no further modifications in neurodevelopment, and no locomotor or exploratory alterations in later developmental stages. Habituation was altered in a sex-dependent manner, but no overall memory disturbances were encountered. Finally, MeHg-VitA co-administration reduced lipoperoxidation in male offspring hippocampus. In conclusion, VitA co-administration in dams, under our exposure protocol, can counteract the deleterious neurodevelopmental effects solely attributed to low-dose MeHg in a tissue-specific mechanism, suggesting a protective effect of VitA against MeHg-induced oxidative damage in the central nervous system, especially in the offspring. Further work is needed to confirm our findings and elucidate the molecular mechanisms of MeHg-VitA modulation. Pre-clinical assays are necessary to demonstrate the potential therapeutical use of VitA in populations directly or indirectly exposed to MeHg.