Efficacy of Hair Total Mercury Content as a Biomarker of Methylmercury Exposure to Communities in the Area of Artisanal and Small-Scale Gold Mining in Madre de Dios, Peru

Total mercury content (THg) in hair is an accepted biomarker for chronic dietary methylmercury (MeHg) exposure. In artisanal and small-scale gold mining (ASGM) communities, the validity of this biomarker is questioned because of the potential for contamination from inorganic mercury. As mining communities may have both inorganic and organic mercury exposures, the efficacy of the hair-THg biomarker needs to be evaluated, particularly as nations begin population exposure assessments under their commitments to the Minamata Convention. We sought to validate the efficacy of hair THg for public health monitoring of MeHg exposures for populations living in ASGM communities. We quantified both THg and MeHg contents in hair from a representative subset of participants (N = 287) in a large, population-level mercury exposure assessment in the ASGM region in Madre de Dios (MDD), Peru. We compared population MeHg-THg correlations and %MeHg values with demographic variables including community location, sex, occupation, and nativity. We observed that hair MeHg-THg correlations were high (r > 0.7) for all communities, regardless of location or nativity. Specifically, for individuals within ASGM communities, 81% (121 of 150 total) had hair THg predominantly in the form of MeHg (i.e., >66% of THg) and reflective of dietary exposure to mercury. Furthermore, for individuals with hair THg exceeding the U.S. EPA threshold (1.0 μg/g), 88 out of 106 (83%) had MeHg as the predominant form. As a result, had urine THg solely been used for mercury exposure monitoring, approximately 59% of the ASGM population would have been misclassified as having low mercury exposure. Our results support the use of hair THg for monitoring of MeHg exposure of populations in ASGM settings where alternative biomarkers of MeHg exposure are not feasible.

Maternal methylmercury exposure changes the proteomic profile of the offspring’s salivary glands: Prospects on translational toxicology

Background Methylmercury (MeHg) remains a public health issue since developing organisms are particularly vulnerable to this environmental contaminant. This study investigated the effect of maternal MeHg exposure on the modulation of proteomic profile of parotid (PA), submandibular (SM), and sublingual (SL) glands of offspring rats. Materials and methods Pregnant Wistar rats were daily exposed to 40 μg/kg MeHg during both gestational and lactation periods. The proteomic profiles of the major salivary glands of the offspring rats were analyzed through mass spectrometry. Results The offspring rats exposed to MeHg showed significant alterations in the proteomic profiles of the PA, SM, and SL glands. Altered proteins were associated with cytoskeleton components, tissue morphogenesis, and response to stimulus and stress. Conclusion This original study showed that maternal MeHg exposure significantly modulates the expression of proteins and induces alterations in the proteomic profiles of developing salivary glands.

Developmental exposure to methylmercury and ADHD, a literature review of epigenetic studies

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects the competence of academic performance and social wellness in children and adults. The causes of ADHD are unclear. Both genetic and environmental factors contribute to the development of ADHD. The behavioral impairments in ADHD are associated with epigenetic changes in genes that are important for neurodevelopment. Among environmental causes of ADHD, the neurotoxin methylmercury (MeHg) is associated with an increased risk for ADHD. Developing children are susceptible to neurotoxic effects of prenatal MeHg exposure. Human epidemiology studies have shown that prenatal MeHg exposure could invoke epigenetic changes in genes that are involved in ADHD. In addition, the pathogenesis of ADHD involves dopaminergic system, which is a target of developmental MeHg exposure. MeHg-induced alterations in the dopaminergic system have a profound impact on behavioral functions in adults. As a trace level of MeHg (around nM) can induce long-lasting behavioral alterations, potential mechanisms of MeHg-induced functional changes in the dopaminergic system may involve epigenetic mechanisms. Here, we review the relevant evidence on developmental MeHg exposures and the risk for ADHD. We also point out research gaps in understanding environmental causes of ADHD.

Contributing to Understand the Crosstalk between Brain and Periphery in Methylmercury Intoxication: Neurotoxicity and Extracellular Vesicles

Human exposure to methylmercury (MeHg) is currently high in regions such as the Amazon. Understanding the molecular changes associated with MeHg-induced neurotoxicity and the crosstalk with the periphery is essential to support early diagnoses. This work aimed to evaluate cellular and molecular changes associated with behavioral alterations in MeHg acute exposure and the possible changes in extracellular vesicles (EVs) number and S100β content. Adults male Wistar rats were orally treated with 5 mg/kg for four days. Behavioral performance, molecular and histological changes in the cerebellum, and plasma EVs were assessed. MeHg-intoxicated animals performed significantly worse in behavioral tests. MeHg increased the number of GFAP+ cells and GFAP and S100β mRNA expression in the cerebellum but no change in NeuN+ or IBA-1+ cells number was detected. The number of exosomes isolated from plasma were decreased by the metal. S100B mRNA was detected in circulating plasma EVs cargo in MeHg exposure. Though preliminary, our results suggest astrocytic reactivity is displaying a protective role once there was no neuronal death. Interestingly, the reduction in exosomes number could be a new mechanism associated with MeHg-induced neurotoxicity and plasma EVs could represent a source of future biomarkers in MeHg intoxication.

Neurological Impacts of Chronic Methylmercury Exposure in Munduruku Indigenous Adults: Somatosensory, Motor, and Cognitive Abnormalities

There has been increasing evidence about mercury (Hg) contamination in traditional populations from the Amazon Basin due to illegal gold mining. The most concerning health impact is neurotoxicity caused by Hg in its organic form: methylmercury (MeHg). However, the severity and extent of the neurotoxic effects resulting from chronic environmental exposure to MeHg are still unclear. We conducted a clinical-epidemiological study to evaluate the neurological impacts of chronic MeHg exposure in Munduruku indigenous people, focusing on somatosensory, motor, and cognitive abnormalities. All participants were subjected to a systemized neurological exam protocol, including Brief Cognitive Screening Battery (BCSB), verbal fluency test, and Stick Design Test. After the examination, hair samples were collected to determine MeHg levels. Data collection took place between 29 October and 9 November 2019, in three villages (Sawré Muybu, Poxo Muybu, and Sawré Aboy) from Sawré Muybu Indigenous Land, Southwest of Pará state. One hundred and ten individuals >12 years old were included, 58 of which were men (52.7%), with an average age of 27.6 years (range from 12 to 72). Participants’ median MeHg level was 7.4 µg/g (average: 8.7; S.D: 4.5; range: 2.0–22.8). In Sawré Aboy village, the median MeHg level was higher (12.5 µg/g) than in the others, showing a significant statistical exposure gradient (Kruskal–Wallis test with p-value < 0.001). Cerebellar ataxia was observed in two participants with MeHg levels of 11.68 and 15.68 µg/g. Individuals with MeHg exposure level ≥10 µg/g presented around two-fold higher chances of cognitive deficits (RP: 2.2; CI 95%: 1.13–4.26) in BCSB, and in the verbal fluency test (RP: 2.0; CI 95%: 1.18–3.35). Furthermore, adolescents of 12 to 19 years presented three-fold higher chances of verbal development deficits, according to the fluency test (RP: 3.2; CI 95%: 1.06–9.42), than individuals of 20 to 24 years. The worsened motor and cognitive functions are suggestive of neurotoxicity due to chronic MeHg exposure. In conclusion, we believe monitoring and follow-up measures are necessary for chronic mercury exposed vulnerable people, and a basic care protocol should be established for contaminated people in the Brazilian Unified Health System.

Impacts of the Goldmining and Chronic Methylmercury Exposure on the Good-Living and Mental Health of Munduruku Native Communities in the Amazon Basin

This paper is an exploratory study that examines the illegal goldmining impacts on Munduruku communities’ “Good-Living” (Xipan Jewewekukap) and explores the possible relationship between chronic methylmercury (MeHg) exposure and the worsening mental health conditions in three villages in the Middle-Tapajós River, Brazilian Amazon. The region has been experiencing a long-lasting threat of goldminers’ invasions. A total of 109 people were interviewed and evaluated. Total mercury (THg) exposure levels were evaluated through hair samples analysis, from which MeHg exposure levels were calculated. The Geriatric Depression Scale—Short Form (GDS-SF) was used as a screening tool in order to assess mental health indicators. Brief non-structured interviews were carried out to investigate how goldmining is impacting the communities Good-Living. A Poisson regression model was used to estimate the possible association between mental health indicators (assessed through the GDS-SF) and the following independent variables: (i) mercury exposure level (<10.0 μg/g vs. ≥10.0 μg/g), (ii) self-reported nervousness, (iii) self-reported irritability, (iv) age group, and (v) monthly income. The analysis revealed high levels of mercury in hair samples (median: 7.4 µg/g, range 2.0–22.8; 70% and 28% of the participants had THg levels ≥6.0 and ≥10.0 µg/g, respectively) and pointed to a tendency in which higher levels of methylmercury exposure (Hg ≥ 10.0 µg/g) could be linked to worse mental health indicators. Although the GDS-SF has presented limitations due to the Munduruku sociocultural context, our findings suggest a tendency of worse mental health indicators in participants presenting high levels of MeHg exposure. Despite this limitation, the qualitative approach indicates an evident association between the impacts of goldmining and the Munduruku people’s decreasing autonomy to maintain a Good-Living on their own terms, pointing to the importance of carrying out new investigations, especially considering longitudinal studies with qualitative methodologies and ethnographic approaches.

DHA and Its Metabolites Have a Protective Role against Methylmercury-Induced Neurotoxicity in Mouse Primary Neuron and SH-SY5Y Cells

The consumption of fish now involves a risk of methylmercury (MeHg) exposure but also provides the benefit of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) such as docosahexaenoic acid (DHA). Some epidemiological studies have suggested that the intake of DHA can alleviate the neurotoxicity of MeHg, but the underlying mechanism is not known. Herein, we observed that pretreatment with 0.1–1 µM DHA suppressed MeHg-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells and mouse primary neuronal cells. These effects of DHA were canceled in the presence of the retinoid X receptor (RXR) antagonist UVI3003. An RXR agonist, bexarotene, suppressed the cytotoxicity of MeHg. DHA also suppressed the MeHg-induced production of reactive oxygen species (ROS) via an induction of antioxidant genes (catalase and SOD1). Pretreatment with DHA did not change the incorporation of MeHg. We showed previously that in the brain, the intake of DHA increased the level of 19,20-DHDP, which is the metabolite produced by cytochrome P450 and soluble epoxide hydrolase from DHA. In the present study, we observed that 19,20-DHDP also suppressed neurotoxicity from MeHg. These results indicate that DHA and its metabolites have a protective role in MeHg-induced neurotoxicity.

Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg), however, is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

Mercury accumulation in vegetable Houttuynia cordata Thunb. from two different geological areas in southwest China and implications for human consumption

Houttuynia cordata Thunb. (HCT) is a common vegetable native to southwest China, and grown for consumption. The results suggested that THg contents in all parts and MeHg in underground parts of HCT in Hg mining areas were much higher than those in non-Hg mining areas. The highest THg and MeHg content of HCT were found in the roots, followed by the other tissues in the sequence: roots > leaves > rhizomes > aboveground stems (THg), and roots > rhizomes > aboveground stems > leaves (MeHg). The average THg bioaccumulation factor (BCF) of HCT root in the Hg mining area and in non-Hg mining areas could reach 1.02 ± 0.71 and 0.99 ± 0.71 respectively, indicating that HCT is a Hg accumulator. And the THg and MeHg contents in all tissues of HCT, including the leaves, were significantly correlated with THg and MeHg content in the soil. Additionally, preferred dietary habits of HCT consumption could directly affect the Hg exposure risk. Consuming the aboveground parts (CAP) of HCT potentially poses a high THg exposure risk and consuming the underground parts (CUP) may lead to a relatively high MeHg exposure risk. Only consuming the rhizomes (OCR) of the underground parts could significantly reduce the exposure risk of THg and to some extent of MeHg. In summary, HCT should not be cultivated near the Hg contaminated sites, such as Hg tailings, as it is associated with a greater risk of Hg exposure and high root Hg levels, and the roots should be removed before consumption to reduce the Hg risk.