Arsenic-contaminated groundwater used for drinking in China is a health threat that was first recognized in the 1960s. However, because of the sheer size of the country, millions of groundwater wells remain to be tested in order to determine the magnitude of the problem. We developed a statistical risk model that classifies safe and unsafe areas with respect to geogenic arsenic contamination in China, using the threshold of 10 micrograms per liter, the World Health Organization guideline and current Chinese standard for drinking water. We estimate that 19.6 million people are at risk of being affected by the consumption of arsenic-contaminated groundwater. Although the results must be confirmed with additional field measurements, our risk model identifies numerous arsenic-affected areas and highlights the potential magnitude of this health threat in China.

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Groundwater Arsenic Contamination Throughout China

Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals

Arsenic and human health effects: A review.

Neurodegenerative disorders, such as Alzheimer's disease, are a global public health burden with poorly understood aetiology. Neuroinflammation and oxidative stress (OS) are undoubtedly hallmarks of neurodegeneration, contributing to disease progression. Protein aggregation and neuronal damage result in the activation of disease-associated microglia (DAM) via damage-associated molecular patterns (DAMPs). DAM facilitate persistent inflammation and reactive oxygen species (ROS) generation. However, the molecular mechanisms linking DAM activation and OS have not been well-defined; thus targeting these cells for clinical benefit has not been possible. In microglia, ROS are generated primarily by NADPH oxidase 2 (NOX2) and activation of NOX2 in DAM is associated with DAMP signalling, inflammation and amyloid plaque deposition, especially in the cerebrovasculature. Additionally, ROS originating from both NOX and the mitochondria may act as second messengers to propagate immune activation; thus intracellular ROS signalling may underlie excessive inflammation and OS. Targeting key kinases in the inflammatory response could cease inflammation and promote tissue repair. Expression of antioxidant proteins in microglia, such as NADPH dehydrogenase 1 (NQO1), is promoted by transcription factor Nrf2, which functions to control inflammation and limit OS. Lipid droplet accumulating microglia (LDAM) may also represent a double-edged sword in neurodegenerative disease by sequestering peroxidised lipids in non-pathological ageing but becoming dysregulated and pro-inflammatory in disease. We suggest that future studies should focus on targeted manipulation of NOX in the microglia to understand the molecular mechanisms driving inflammatory-related NOX activation. Finally, we discuss recent evidence that therapeutic target identification should be unbiased and founded on relevant pathophysiological assays to facilitate the discovery of translatable antioxidant and anti-inflammatory therapeutics.

https://www.mdpi.com/2076-3921/9/8/743/pdf

ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease.

http://ssu.ac.ir/cms/fileadmin/user_upload/Mtahghighat/tfood/asil-article/r-z/Protective-effect-of-curcumin-against-heavy-metals-induced-liver-damage_2014_Food-and-Chemical-Toxicology.pdf

Protective effect of curcumin against heavy metals-induced liver damage.

Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus.

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Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats.

Objectives Pneumoconiosis remains a major global occupational health hazard and illness. Accurate data on the incidence of pneumoconiosis are critical for health resource planning and development of health policy. Methods We collected data for the period between 1990 and 2017 on the annual incident cases and the age-standardised incidence rates (ASIR) of pneumoconiosis aetiology from the Global Burden of Disease Study 2017. We calculated the average annual percentage changes of ASIR by sex, region and aetiology in order to determine the trends of pneumoconiosis. Results Globally, the number of pneumoconiosis cases increased by a measure of 66.0%, from 36 186 in 1990 to 60 055 in 2017. The overall ASIR decreased by an average of 0.6% per year in the same period. The number of pneumoconiosis cases increased across the five sociodemographic index regions, and there was a decrease in the ASIR from 1990 to 2017. The ASIR of silicosis, coal workers’ pneumoconiosis and other pneumoconiosis decreased. In contrast, measures of the ASIR of asbestosis displayed an increasing trend. Patterns of the incidence of pneumoconiosis caused by different aetiologies were found to have been heterogeneous for analyses across regions and among countries. Conclusion Incidence patterns of pneumoconiosis which were caused by different aetiologies varied considerably across regions and countries of the world. The patterns of incidence and temporal trends should facilitate the establishment of more effective and increasingly targeted methods for prevention of pneumoconiosis and reduce associated disease burden.

https://oem.bmj.com/content/oemed/early/2020/03/18/oemed-2019-106321.full.pdf

Trends in global, regional and national incidence of pneumoconiosis caused by different aetiologies: an analysis from the Global Burden of Disease Study 2017

Excessive exposure to fluoride results in structural and functional damages to the central nervous system (CNS), and neurotoxicity of fluoride may be associated with neurodegenerative changes. Chronic microglial activation appears to cause neuronal damage through producing proinflammatory cytokines and is involved in many neurodegenerative disorders. It is not known about effects on microglia of fluoride. In the present study, healthy adult Wistar rats were exposed to 60 and 120 ppm fluoride in drinking water for 10 weeks, and control rats received deionized water. After 10 weeks, rats were sacrificed under anesthesia then apoptosis in neuron and inflammatory factors secreted by microglia were determined. We found that apoptosis of neurons in fluoride-treated rat brain increased and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive immunofluorescence increased with increasing fluoride concentrations. Bax protein expression increased and Bcl-2 protein expression decreased in fluoride-treated rat brain compared with that of the control rat brain. The microglia in the hippocampus and cortex of fluoride-treated rats were activated by immunostaining with OX-42, a marker of activated microglia, and OX-42-positive microglia cells were more abundant in the hippocampus than in the cortex. The levels of IL-1β and IL-6 protein expression in OX-42-labeled microglial cells were significantly increased in the cortex and hippocampus of rats exposed to fluoride, and TNF-α immunoreactivity in microglial cells of the hippocampus was significantly higher in the 120 ppm fluoride-treated group than that in the control group. Our results indicate that fluoride induced neuron apoptosis and expressions of inflammatory factors by activating microglia in rat brain.

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Prolonged exposure to inorganic arsenic has been a severe environmental public health issue worldwide in the recent decades. Increasing evidence has suggested a possible role of prolonged arsenic exposure through drinking water in the development of arsenic-induced chronic noncancer diseases, among which hypertension and type 2 diabetes (T2D) are the focus of concern. Although exposure to high levels of arsenic has been reported to be associated with excess risk of hypertension or T2D in a dose-dependent manner, the association has yet to be established, especially low-level exposure. This cross-sectional study was designed to evaluate the potential association between prolonged environmental arsenic exposure through drinking water and the prevalence of hypertension and T2D in Inner Mongolia, China, with emphasis on the assessment of low-level exposure. In this study (a total of 669 men and women), we found that the blood pressure levels were significantly correlated with cumulative arsenic exposure and that the systolic blood pressure of the subjects with arsenic exposure>50 μg/L was significantly higher than those of the subjects with 50 μg/L group both before and after adjustment for confounders. In addition, a significant negative relationship was found between urinary arsenic percentage of dimethylated arsenic (DMA%) and the prevalence of hypertension in the >50 μg/L group. However, low-level arsenic exposure (10-50 μg/L) was not statistically associated with hypertension. No significant difference of blood glucose was found among the groups with different arsenic exposure levels. No statistical association was found between arsenic exposure and T2D. Our findings suggested that prolonged arsenic exposure might play a role in the development of hypertension; however, only high-level arsenic was associated with the risk of hypertension. Our findings also indicated that lower DMA% might be related with the increased susceptibility of arsenic-induced hypertension.

Prolonged environmental exposure of arsenic through drinking water on the risk of hypertension and type 2 diabetes.

Although some studies mainly from Taiwan, Bangladesh and the United States, have suggested a consistent dose–response increase in the prevalence of hypertension with increasing arsenic exposure, the association between chronic environmental arsenic exposure and the risk of hypertension is still inconclusive. Most of the studies discussed the association from the point of view of arsenic concentration in drinking water or cumulative arsenic exposure (CAE), few involved arsenic speciation into the discussion. In this cross-sectional study, we evaluated the potential association between environmental arsenic exposure through drinking water and the prevalence of hypertension by analyzing not only CAE but also urinary arsenic speciation, and provided data on arsenic exposure and hypertension from mainland of China. A cross-sectional study was conducted in one of the arsenic contaminated areas in the northwest of China. Among a total of 1005 residents who voluntarily participated in the study, 604 of eligible subjects were confirmed and interviewed door to door. Standing height, body weight, and blood pressure were measured. First void urine was collected and measured for the concentration of urinary arsenic speciation. CAE was calculated in a subpopulation of 360 subjects with detailed water consumption history. The association between urinary arsenic speciation, CAE and the risk of hypertension were analyzed by multiple logistic regressions. We found that the levels of urinary arsenic species of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) and total arsenic (tAs) were significantly correlated with systolic or pulse blood pressure. A positive relationship was found between the highest tertile of CAE and hypertension in a dose-dependent manner. Subjects with higher concentration of urinary MMA or lower percentage of DMA tended to be liable to suffer from hypertension. A significant increasing trend of the risk of hypertension with increasing tertiles of MMA concentration was also observed in the logistic regression models both before and after adjustment for confounders. Our findings suggested that arsenic exposure, especially high level of CAE, was positively associated with the prevalence of hypertension, and that higher concentration of urinary MMA might be related to the increased susceptibility to hypertension.

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Association of urinary monomethylated arsenic concentration and risk of hypertension: a cross-sectional study from arsenic contaminated areas in northwestern China

Shuhua Xi

Papers

Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats.

Trends in global, regional and national incidence of pneumoconiosis caused by different aetiologies: an analysis from the Global Burden of Disease Study 2017

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Prolonged environmental exposure of arsenic through drinking water on the risk of hypertension and type 2 diabetes.

Association of urinary monomethylated arsenic concentration and risk of hypertension: a cross-sectional study from arsenic contaminated areas in northwestern China