Low Arsenic Exposure Research Articles

Toxic Metals Impact Gut Microbiota and Metabolic Risk in Five African-Origin Populations.

Exposure to toxic metals impacts obesity and type 2 diabetes (T2DM) risk. Yet, the underlying mechanisms remain largely unknown. Gut microbiota has been strongly associated with progression of cardiometabolic risk. To determine whether high metal exposures and gut dysbiosis interact to promote metabolic dysregulation and cardiometabolic risk, we assessed relationships between these factors. We analyzed cross-sectional associations between arsenic, lead, mercury, cadmium, and cardiometabolic health markers in 178 randomly selected African-origin adults (52% female, 51% obese, mean age=43.0±6.4 years) from Ghana, South Africa, Seychelles, Jamaica, and USA. Metal levels were dichotomized to high or low at the median level of each metal. We analyzed associations between gut microbiome taxa, metal levels, clinical measures (BMI, fasting blood glucose, and blood pressure) and diagnoses (hypertension, obesity, and diabetes status). High vs. low lead and arsenic exposures had a significant effect on beta diversity (p <0.05). 71 taxa were associated with high lead levels: 30 with elevated BMI, 22 with T2DM, and 23 with elevated fasting blood glucose (p<0.05). 115 taxa were associated with high arsenic levels: 32 with elevated BMI, 33 with T2DM, and 26 with elevated blood glucose (p<0.05). Of the taxa associated with high lead and arsenic exposure and either elevated BMI or fasting blood glucose, porphyrin metabolism was the most enriched metabolic pathway. These data collectively provide the first findings in a human study that the gut microbiome may drive the association between lead and arsenic exposure and obesity and T2DM risk.

Rapid and noninvasive estimation of human arsenic exposure based on 4-photo-set of the hand and foot photos through artificial intelligence

Chronic exposure to arsenic is linked to the development of cancers in the skin, lungs, and bladder. Arsenic exposure manifests as variegated pigmentation and characteristic pitted keratosis on the hands and feet, which often precede the onset of internal cancers. Traditionally, human arsenic exposure is estimated through arsenic levels in biological tissues; however, these methods are invasive and time-consuming. This study aims to develop a noninvasive approach to predict arsenic exposure using artificial intelligence (AI) to analyze photographs of hands and feet. By incorporating well water consumption data and arsenic concentration levels, we developed an AI algorithm trained on 9988 hand and foot photographs from 2497 subjects. This algorithm correlates visual features of palmoplantar hyperkeratosis with arsenic exposure levels. Four pictures per patient, capturing both ventral and dorsal aspects of hands and feet, were analyzed. The AI model utilized existing arsenic exposure data, including arsenic concentration (AC) and cumulative arsenic exposure (CAE), to make binary predictions of high and low arsenic exposure. The AI model achieved an optimal area under the curve (AUC) values of 0.813 for AC and 0.779 for CAE. Recall and precision metrics were 0.729 and 0.705 for CAE, and 0.750 and 0.763 for AC, respectively. While biomarkers have traditionally been used to assess arsenic exposure, efficient noninvasive methods are lacking. To our knowledge, this is the first study to leverage deep learning for noninvasive arsenic exposure assessment. Despite challenges with binary classification due to imbalanced and sparse data, this approach demonstrates the potential for noninvasive estimation of arsenic concentration. Future studies should focus on increasing data volume and categorizing arsenic concentration statistics to enhance model accuracy. This rapid estimation method could significantly contribute to epidemiological studies and aid physicians in diagnosis.

Chronic low arsenic exposure in private wells and early markers of diabetes and cardiovascular health

Chronic low arsenic exposure in private wells and early markers of diabetes and cardiovascular health

Dictyophora polysaccharides alleviate intestinal-hepatic injury exposed to low-arsenic by regulating the imbalance of gut microbiota and LPS/TLR4 pathway in rats

Intestinal and liver damage caused by low arsenic exposure exists in worldwide, but the pathogenic mechanism is not clear at present.Dictyophora is a characteristic edible and medicinal fungus in China, and research has shown that its polysaccharides have good prebiotic effects.Therefore,we explored whether volva polysaccharide from Dictyophora has a certain therapeutic effect and its mechanism on intestinal and hepatic injury caused by low arsenic exposure.Firstly,we constructed the SD rat model of enteritis caused by low arsenic-induced.Then, from the perspectives of inflammatory responses capacity,histological alterations and serum biochemical levels of rats by arsenic-exposed with DIP intervention are analyzes the possible mechanism of intestinal and liver injury.Besides, the caecal microbiomes patterns were analysed using 16 S rDNA amplicon sequencing.Results showed that dictyophora polysaccharide increased the abundance of beneficial bacteria such as Turicibacter, Oscillospiraceae_UCG-005,and reduced the abundance of Desulfovibrionia and Lachnospiraceae_NK4A136_group proinflammatory bacteria.After dictyophora polysaccharide intervention, the pathological changes of liver and colon were alleviated,and the levels of triglyceride, total cholesterol,and lipopolysaccharide in hepatic portal vein, total arsenic contents in the liver and colon tissues were reduced. Finally,we also found after dictyophora polysaccharide intervention,the gene and protein expression of Toll-like receptor 4 was returned to normal level,and the expression levels of pro-inflammatory factors in liver and colon were reduce. In summary, our study found that dictyophora polysaccharide alleviated intestinal and hepatic injury in rats exposed to low arsenic by regulated intestinal microbiota and reduced TLR4 activation, which inhibited downstream proteins MyD88 to reduce the nuclear translocation of the NF-κB p65 genes and protein.

Associations of Maternal Urinary Arsenic Concentrations during Pregnancy with Infant and Child Mental, Psychomotor, and Cognitive Development: The HOME Study

Background and aims Arsenic exposure during pregnancy may increase the risk for intellectual deficits in children, but limited data exists from prospective epidemiologic studies, particularly at low arsenic exposure levels. We investigated the association between prenatal urinary arsenic concentrations and childhood cognitive abilities in the Health Outcomes and Measures of the Environment (HOME) Study. Methods We used anion exchange chromatography coupled with inductively coupled plasma mass spectrometry detection to measure arsenic species content in pregnant women’s urine. The summation of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) refers to ∑As. We longitudinally assessed children’s cognitive function (n = 260) longitudinally at 1, 2, and 3 years using Bayley Scales of Infant and Toddler Development, at 5 years using Wechsler Preschool and Primary Scale of Intelligence, and at 8 years using Wechsler Intelligence Scale for Children. Results We observed a modest decrease in mental development index and full-scale intelligence quotient at ages 3 and 5 years with each doubling of ∑As (median and IQR of 3.63 and 2.40-5.86 µg/L) with estimated score (ß) differences and 95% confidence interval (CI) of -1.8 from -4.1 to 0.5 and -2.5 from -5.1 to 0.0, respectively. This trend was stronger among children whose mothers had lower iAs methylation capacity and low urinary arsebonetaine concentrations. Conclusions Our findings suggest that exposure levels relevant to the general US population may adversely affect children’s cognitive abilities. Keywords arsenic; neurodevelopment; cognitive; Bayley Scale of Infant Development; Wechsler Preschool and Primary Scale of Intelligence; in utero exposure; Mental development index; Full scale intelligence quotient.

Associations of maternal urinary arsenic concentrations during pregnancy with childhood cognitive abilities: The HOME study.

Arsenic exposure during pregnancy may increase the risk for intellectual deficits in children, but limited data exist from prospective epidemiologic studies, particularly at low arsenic exposure levels. We investigated the association between prenatal maternal urinary arsenic concentrations and childhood cognitive abilities in the Health Outcomes and Measures of the Environment (HOME) Study. We used anion exchange chromatography coupled with inductively coupled plasma mass spectrometry detection to measure arsenic species content in pregnant women’s urine. The summation of inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) refers to . We assessed children’s cognitive function (n = 260) longitudinally at 1-, 2-, and 3-years using Bayley Scales of Infant and Toddler Development, at 5 years using Wechsler Preschool and Primary Scale of Intelligence, and at 8 years using Wechsler Intelligence Scale for Children. We observed a modest decrease in mental development index and full-scale intelligence quotient at ages 3 and 5 years with each doubling of with estimated score (ß) differences and 95% confidence interval (CI) of −1.8 from −4.1 to 0.5 and −2.5 from −5.1 to 0.0, respectively. This trend was stronger and reached statistical significance among children whose mothers had lower iAs methylation capacity and low urinary arsenobetaine concentrations. Our findings suggest that arsenic exposure levels relevant to the general US population may affect children’s cognitive abilities.

Effects of prenatal exposure to arsenic on neonatal birth size in Wujiang, China

To investigate prenatal exposure to arsenic and its effect on birth size, we conducted a cross-sectional study in Wujiang City, Jiangsu, China, from June 2009 to June 2010. A total of 1722 mother-infant pairs were included in the study. A questionnaire was administered to the pregnant women and umbilical cord blood(UCB) samples were collected. Arsenic concentration in UCB was detected by inductively coupled plasma emission mass spectroscopy (ICP-MS). The birth size included birth weight, birth body length and head circumference of the newborns. The effects of arsenic exposure on birth size were assessed by multiple linear regression analysis. Arsenic concentrations in UCB ranged from 0.11 to 30.36 μg/L, the median was 1.71 μg/L. In this range of exposure, arsenic concentration was significantly negatively associated with birth weight, especially among male infants. Our results showed that prenatal exposure to arsenic level was low in Wujiang City, China. However, low prenatal arsenic exposure could have negative effects on birth weight. Our research provided evidence for the adverse effects of prenatal low-level arsenic exposure on the intrauterine growth of the fetus.

Early Low-Level Arsenic Exposure Impacts Post-Synaptic Hippocampal Function in Juvenile Mice.

Arsenic is a well-established carcinogen known to increase mortality, but its effects on the central nervous system are less well understood. Epidemiological studies suggest that early life exposure is associated with learning deficits and behavioral changes. Studies in arsenic-exposed rodents have begun to shed light on potential mechanistic underpinnings, including changes in synaptic transmission and plasticity. However, previous studies relied on extended exposure into adulthood, and little is known about the effect of arsenic exposure in early development. Here, we studied the effects of early developmental arsenic exposure in juvenile mice on synaptic transmission and plasticity in the hippocampus. C57BL/6J females were exposed to arsenic (0, 50 ppb, 36 ppm) via drinking water two weeks prior to mating, with continued exposure throughout gestation and parturition. Electrophysiological recordings were then performed on juvenile offspring prior to weaning. In this paradigm, the offspring are exposed to arsenic indirectly, via the mother. We found that high (36 ppm) and relatively low (50 ppb) arsenic exposure both decreased basal synaptic transmission. A compensatory increase in pre-synaptic vesicular release was only observed in the high-exposure group. These results suggest that indirect, ecologically relevant arsenic exposure in early development impacts hippocampal synaptic transmission and plasticity that could underlie learning deficits reported in epidemiological studies.

Histopathological Changes in Chronic Low Dose Organic Arsenic Exposure in Rats Kidney

INTRODUCTION: Exposure to environmental arsenic remains a major public health challenge. Human is exposed to arsenic from groundwater as a result of anthropogenic activities. Chronic exposure to inorganic arsenic has been linked with multiple medical conditions. Therefore, many agricultural countries have shifted the use of inorganic to the organic-based herbicide, monosodium methylarsonate (MSMA). However, with increasing numbers of chronic kidney disease of unknown etiology (CKDu), chronic exposure to herbicide is believed as one of the potential explanations. To date, studies on chronic effects of organic arsenic on the kidney are limited. Therefore, this study aimed to investigate the effect of chronic oral organic arsenic exposure on the rat’s kidney. MATERIALS AND METHOD: Thirty-six Sprague Dawley rats were randomly divided into treatment and its corresponding control groups according to the duration of observations either 2, 4 or 6 months. Both groups were subdivided into three subgroups, each with six animals per subgroup. The treatment groups were given oral MSMA at 63.20 mg/kg body weight, while control groups received distilled water. At the end of each duration, blood was collected for the renal profile, urine for neutrophil gelatinase-associated lipocalin (NGAL) marker, and kidney tissues were harvested for arsenic level measurement and histological analysis. RESULTS:Arsenic level and urinary NGAL were higher in all treatment groups than its corresponding control groups. Histological findings showed progressive pathological changes in the glomeruli and proximal tubules. CONCLUSIONS:Chronic oral exposure to low dose organic arsenic has demonstrated evidence of kidney injury in rats.

Effect of Arsenic Toxicity on Chlorophyll Content and Antioxidative Enzymes Activities in Rice Seedlings

Aims: Arsenic (As) contamination in rice is at alarming level as majority of rice growing regions in India are As contaminated. Present investigation is designed to study the better understanding of the physiological and biochemical mechanisms in the amount of chlorophyll change and antioxidative enzymes activity under arsenic stress on rice variety IET-4786 (Shatabdi).&#x0D; Study Design: Completely Randomized Design.&#x0D; Place and Duration of Study: The experiment was carried out in the departmental laboratory of Plant Physiology, Bidhan Chandra Krishi Viswavidyalaya (BCKV), Mohanpur, Nadia,West Bengal during the year 2017-18.&#x0D; Methodology: Two classes of inorganic arsenic- As(V) in the form of Sodium arsenate (Na2HAsO4.7H2O, M. W. = 321.01) and As(III) in the form of Sodium arsenite (NaAsO2, M.W. =129.91) were added to the modified Hoagland nutrient solution@ 2.5, 5.0, 7.5, 10.0, 12.5,15.0 mg L-1concentration. After 20 days of treatment, rice seedlings under arsenate/arsenite treatments were analyzed for change in total chlorophyll content and antioxidative enzymes activity such as superoxide dismutase (SOD: EC 1.15.1.1), catalase (CAT: EC 1.11.1.6), ascorbate peroxidase (APX: EC1.11.1.11) and peroxidase (POD: EC 1.11.1.7).&#x0D; Results: A noticeable decrease in total chlorophyll content was observed with arsenic treatments as compared to control. Various antioxidative enzymes showed significant variable response upon exposure to As(III) and As(V). SOD activities increased at low arsenic exposure up to 7.5 mg L-1 but decreased with further increase in arsenic treatments. APX and POD activities were increased with increase in arsenic concentrations while CAT activity displayed decreasing trend.&#x0D; Conclusion: The results are suggestive of differential metabolism of As(III) and As(V) in rice and could exert harmfulness in the early development stage of rice at inappropriate concentrations.

Association of low blood arsenic exposure with level of malondialdehyde among Chinese adults aged 65 and older

High environmental arsenic exposure can increase chronic oxidative stress in experimental studies and in occupational epidemiology studies. Many regulatory agencies have put forth arsenic exposure limits, it is still unclear that whether low environmental arsenic exposure was associated with adverse health outcome in general population. This study aimed to explore the association of low blood arsenic with malondialdehyde in community-dwelling older adults. We used a cross-sectional study of 2384 older adult individuals aged ≥65 years (mean age: 85 years) from the Healthy Aging and Biomarkers Cohort Study in 2017. The median blood arsenic level was 1.41 μg/L. High oxidative stress was categorized according to the 95th percentile of MDA levels (7.47 nmol/mL). Restricted cubic spline models showed that blood arsenic levels were positively associated with malondialdehyde levels (P < 0.01); and the risk of high oxidative stress was no longer significantly increased when blood arsenic level up to 8.74 μg/L. After adjusting for potential confounders, the odds ratios of high oxidative stress for the second, third, and fourth quartiles of blood arsenic were 2.35 (1.11–4.96), 3.87 (1.90–7.91), and 4.18 (2.00–8.72) (Ptrend < 0.01), compared with the first quartile. We concluded that even low arsenic exposure was associated with higher risk of oxidative stress, in a nonlinear dose-response.

Chronic Low Dose Organic Arsenic Induced Liver Structural Damage

Introduction: Over the decades, organic arsenic has been thought to be less toxic than inorganic arsenic. Monosodium methylarsonate (MSMA) is a potent organoarsenical herbicide that is still being used in most Asian countries. Reported studies on the effects of organic arsenic are mainly to the gastrointestinal system, however there are limited research on its impacts to the liver. Therefore, this study aimed to investigate the effect of MSMA exposure on hepatocytes and liver sinusoidal endothelial cells (LSEC). Materials and Methods: Fourteen Sprague Dawley rats (n=14) were divided equally into arsenic-exposed (n=7) and control (n=7) groups. The rats in arsenic-exposed group were given MSMA at 63.20 mg/kg daily for 6 months through oral gavage. While the rats in control group were given distilled water ad libitum. At the end of the duration, they were euthanized and underwent liver perfusion for tissue preservation. Liver tissues were harvested and processed for light microscopy, scanning and transmission electron microscopy. The findings were analysed descriptively. Results: MSMA had caused necrotic and apoptotic changes to the liver. Normal organelles morphology were loss in the hepatocytes while LSEC revealed defenestration. Conclusion: In this study, chronic low dose organic arsenic exposure showed evidence of toxicity to hepatocytes. Interestingly, LSEC demonstrated capillarization changes.

Association betweenrice consumption andrisk of cancer incidence in the California Teachers Study.

We evaluated the contribution of rice intake, a source of dietary arsenic, to cancer risk in a population of women with likely low arsenic exposure from drinking water and variable rice intake who participated in the California Teachers Study. Rice consumption was categorized into quartiles (< 9.6, 9.7-15.6, 15.7-42.7, and ≥ 42.8g/day). Multivariable-adjusted hazard ratios and 95% confidence intervals (95% CI) for incident cancer were estimated comparing rice consumption categories with bladder, breast, kidney, lung, and pancreatic cancer, with progressive adjustment for age, total calories, BMI, race, smoking status, physical activity, and cancer-specific covariates. The number of breast, lung, pancreatic, bladder, and kidney cancer cases was 7,351; 1,100; 411; 344; and 238, respectively. The adjusted hazard ratios (95% CI) comparing the highest versus lowest rice intake quartiles were 1.07 (1.00-1.15); 0.87 (0.72-1.04); 0.95 (0.66-1.37); 1.11 (0.81-1.52) and 1.07 (0.72-1.59) for breast, lung, pancreatic, bladder, and kidney cancers, respectively. Results were consistent when rice was modeled as a continuous variable and in analyses stratified by smoking status. Rice consumption was not associated with risk of kidney, lung or pancreatic cancer, except maybe a small excess risk for breast cancer and a small non-significant excess risk for bladder cancer, comparing the highest versus lowest quartile of rice intake. Due to lower consumption patterns in this cohort, future studies should involve populations for which rice is a staple food and use of an arsenic biomarker.

Chronic arsenic exposure enhances metastatic potential via NRF2-mediated upregulation of SOX9

Chronic low dose arsenic exposure continues to be a worldwide health concern because of its prevalence and link to increased cancer risk, including non-small cell lung cancer (NSCLC). Mortality of NSCLC patients increases with the development of a metastatic lesion compared to when the tumor is localized; however, the exact mechanism for what causes NSCLC cells to metastasize in the context of environmental toxicant exposure has yet to be fully elucidated. One proposed contributor to metastasis in NSCLC is nuclear factor (erythroid-derived 2)-like 2 (NRF2), a transcription factor with known oncogenic properties that has proved to be critical for arsenic carcinogenesis. Here, we demonstrate that chronic arsenic exposure enhances the invasive and migratory capacity of immortalized lung epithelial cells via NRF2-dependent upregulation of SRY-box 9 (SOX9), another transcription factor linked with cell proliferation, epithelial-mesenchymal transition, and metastasis. We identified a functional antioxidant response element (ARE) in the promoter region of SOX9, suggesting that it is an NRF2 target gene, with mutation of the ARE preventing NRF2 binding. Pharmacological induction or inhibition of NRF2 increased or decreased SOX9 expression, respectively. Furthermore, we demonstrate that hyperactivation of NRF2 via knockout of Kelch-like ECH-associated protein 1 (KEAP1), its negative regulator, contributes to proliferation; while, inhibition of NRF2 or direct knockdown of SOX9 slowed the ability of NSCLC cells to proliferate, migrate, and invade. Overall, this study suggests that NRF2-mediated SOX9 upregulation can contribute to the metastatic potential of both environmentally and genetically driven lung tumors.

Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma

Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08–1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.

Risk assessment of low arsenic exposure using biomarkers of oxidative and genotoxic stress in a piscine model.

The high level exposure to arsenic induces marked oxidative and genotoxic stress. However, information on the potential of low level arsenic exposure in this context is still scanty. In the present study, the extent of oxidative stress and genetic toxicity induced by low arsenic exposure was explored in freshwater fish Channa punctatus. Fish were exposed to low levels of arsenic (10 and 50 µg L-1) as well as to its high level (500 µg L-1) using sodium arsenite in aquaria water for 14 consecutive days. The TBARS assay for lipid peroxidation exhibited the increased occurrence of oxidative damage in the erythrocytes of fish at both the lower and higher levels of arsenic exposure. The level of reduced glutathione was also elevated in all the three arsenic exposed groups of fish compared to control. In contrast, significant decline was observed in the levels of three major antioxidant enzymes namely, superoxide dismutase, catalase and glutathione peroxidase, upon exposure to higher as well as lower levels of arsenic. Significant increases in micronucleus induction were found in the erythrocytes of fish even at the low levels of arsenic exposure. The study further revealed the occurrence of DNA fragmentation in the erythrocytes of fish at low arsenic exposures as well. The low level exposure to arsenic (using sodium arsenite), therefore, appeared to be capable of inducing noticeable oxidative stress as well as potential genotoxic effect in Channa punctatus. Moreover, the ability of arsenic to induce oxidative stress invariably appeared correlated with its genotoxic potential.

Bi-directional regulation of TGF-β/Smad pathway by arsenic: A systemic review and meta-analysis of in vivo and in vitro studies

BackgroundArsenic exposure can cause fibrosis of organs including the liver, heart and lung. It was reported that TGF-β/Smad pathway played a crucial role in the process of fibrosis. However, the mechanism of arsenic-induced fibrosis through TGF-β/Smad signaling pathway has remained controversial. ObjectiveA systematic review and meta-analysis was performed to clarify the relationship between arsenic and TGF-β/Smad pathway, providing a theoretical basis of fibrosis process caused by arsenic. MethodsA meta-analysis was used to reveal a correlation between arsenic and fibrosis markers of TGF-β/Smad pathway, including 47 articles of both in vivo and in vitro studies. (Standardized Mean Difference) SMD was employed to compare and analyze the combined effects. When I2 > was 50%, random effect model was selected and subgroup analysis was used to explore the source of heterogeneity. ResultsArsenic exposure up-regulated the expression of TGF-β1, p-Smad2/3, α-SMA, Collagen1/3 and FN. The dose-response relationship showed that low dose (≤5 μmol/L) arsenic exposure up-regulated the expression of TGF-β1, whereas high doses had a tendency to down-regulate that of TGF-β1. Subgroup analysis showed that low or short-term arsenic exposure induced the expression of TGF-β1 and fibrosis markers. ConclusionThe results indicated that arsenic activates the TGF-β/Smad pathway and induced fibrosis. The mechanism is related to the up-regulation of NADPH oxidase and ROS accumulation. However, high-dose arsenic exposure may inhibit this pathway.

Health Risk Assessment in Children by Arsenic and Mercury Pollution of Groundwater in a Mining Area in Sonora, Mexico

A highly acidic spill from one of the most important copper mines in the Americas (Buenavista del Cobre) occurred in Sonora, Mexico in August, 2014. 40,000 m3 of metals-enriched sulphate solution escaped into the Sonora River representing the worst ecological disaster in Mexican history. The spill affected the economy, water accessibility and the health of residents near the river. Despite the economic importance of mining in this area, no environmental assessment was undertaken. There is no information about the health impact of this event on the local population. The study assesses the health risk among children exposed to arsenic and mercury via groundwater in five communities located in a mining area into the Sonora River Basin, Mexico. Local drinking water from the localities was sampled one year after the spill and it was analyzed for arsenic and mercury by Atomic Absorption Spectrometry coupled with Hydride Generation (AAS/HG). Further, some of the traditional local foods were sampled and analyzed for the same elements. Results indicate that levels of arsenic in drinking water did not exceed the Mexican Norm (25 μg As/L) or the EPA Guideline (10 μg As/L). The concentrations of mercury exceeded the WHO and Mexican Legislation value (1.0 μg Hg/L). The Hazard Quotient (HQ) values for arsenic were >1 in 42% of children exposed and for mercury in 67% of the children. Foods concentrations contained in the ranges of 9.2 to 62.0 μg As/Kg and 0.28 to 42 μg Hg/Kg for arsenic and mercury respectively. These values are below the Codex Alimentarius limits. Children affected by mining activities are at risk of developing chronic diseases associated with low arsenic and mercury exposure via groundwater consumption, without consideration of the contribution from these metals by other important exposures routes.

Chronic low dose arsenic exposure preferentially perturbs mitotic phase of the cell cycle

Environmental pollution is a big challenge for human survival. Arsenic compounds are well-known biohazard, the exposure of which is closely linked to onsets of various human diseases, particularly cancers. Upon chronically exposing to arsenic compounds, genomic integrity is often disrupted, leading to tumor development. However, the underlying mechanisms by which chronic, low dose arsenic exposure targets genetic stability to initiate carcinogenesis still remain not fully understood. In this study, human lung epithelial BEAS-2B cells and keratinocytes were treated with 0.5 μM of sodium arsenite for one month (designated as BEAS-2B-SA cells or keratinocytes-SA), and its effect on cell cycle responses was analyzed. After being arrested in mitotic phase of the cell cycle by nocodazole treatment, BEAS-2B-SA cells or keratinocytes-SA were delayed to enter next cytokinesis. The lagging exit of the cells from mitosis was accompanied by a sustained Plk1 phosphorylation, which led to a persistent activation of the mitotic regulators BubR1 and Cdc27. As the result, cyclin B1 (clnB1) degradation was attenuated. BEAS-2B-SA cells or keratinocytes-SA also expressed a constitutively active Akt. The cytogenetic analysis showed an increased numbers of aneuploidy in these cells. The suppression of Akt reversed the aberrant expressions of the mitotic regulators, delay of mitotic exit as well as chromosomal aberrations. Our findings suggest that a long-term exposure to low dose sodium arsenite aberrantly retains the catenation of mitosis, which facilitates establishing genetic instability and predisposes the cells to tumorigenesis.

Using the Apolipoprotein E Knock-Out Mouse Model to Define Atherosclerotic Plaque Changes Induced by Low Dose Arsenic.

Arsenic exposure increases the risk of atherosclerosis, the gradual occlusion of the large arteries with fibro-fatty plaque. While epidemiologic data provide convincing evidence this is true at higher exposures, it is unclear whether this may occur at low arsenic exposures, near the maximum contaminant level of 10 ppb. We have previously shown that 200 ppb arsenite in the drinking water increased the atherosclerosis in apolipoprotein E knock-out (apoE-/-) mice after 13 weeks, but the effects of lower concentrations were unknown. Therefore, here, we analyzed the effects of oral exposure to arsenite from 10 to 200 ppb after 13 weeks. Importantly, we found that even at the lowest concentration of arsenite, there was a significant increase in atherosclerotic plaque size. In our previous studies, we found that arsenite exposure resulted in decreased smooth muscle cells (SMCs) and collagen within the plaque. This change is indicative of a less stable phenotype that could increase the risk of rupture and subsequently, myocardial infarct or stroke in humans. In addition, we observed that lipid increased within the plaque without concomitant increase in macrophage content, suggesting that the macrophages were retaining more lipid intracellularly. We also assessed these plaque components in apoE-/- mice exposed to 10-200 ppb arsenite. Interestingly, we observed that macrophage lipid accumulation occurred at lower concentrations than the decreased SMC/collagen content. Together these data suggest that in the apoE-/- model, low arsenite concentrations are pro-atherogenic and that macrophage lipid homeostasis is more sensitive to arsenite-induced perturbation than the SMCs.