Arsenic (As) can occur naturally in groundwater without an anthropogenic source of contamination. Groundwater pumped from approximately half of the roughly 10 million tubewells in Bangladesh do not meet the World Health Organization (WHO) guideline for As of 10 μg/L . Many other countries around the world are also affected by elevated levels of As in drinking water including Chile, Mexico, Mongolia, Nepal, Vietnam, India, Taiwan, China, and the United States . Exposure to elevated levels of inorganic As (As) is associated with cancers of the skin, bladder, and lung[3–5], developmental effects [6, 7], cardiovascular disease [8, 9], skin lesions [10, 11], and decreased intellectual function in children [7, 12, 13].
In contrast, selenium (Se) is an essential mineral for human health which occurs in plants such as corn, wheat, and soybean. These selenocompounds include selenite, selenate, selenocystine, selenomethionine, selenohomocysteine, and Se-methylselenocysteine . It is thought that selenate is reduced to selenite then to selenide by reduced glutathione . Selenium is important for the reduction of hydrogen peroxide and damaging lipid and phospholipids into harmless products via the Se dependent enzyme, glutathione peroxidase (GPx) . In addition to GPx other major groups of selenoproteins include include thioredoxin reductase, iodothyronine deiodinase,and selenoprotein P [17, 18].
The maximum contaminant level (MCL) for Se specified by the Environmental Protection Agency is 0.05 mg/L . Previous studies of individuals accidently ingesting toxic levels of Se containing products with a total dose ranging from 27 to 2387 mg had the following symptoms: nausea, vomiting, nail changes, hair loss, fatigue, breath smelling like garlic, diarrhea, and abdominal cramping . In addition, in selenosis endemic areas of China studies have found disorders of the nervous system and paralysis [21, 22].
The antagonistic relationship between As and Se was first report by Moxon in 1938 when he discovered that As protected against Se toxicity . This effect has since been observed in rats, rabbits, dogs, swine, and cattle . Studies have indicated that Se and As facilitate the excretion of each other in bile [25, 26]. A metabolic link between arsenite and selenite has been identified in the bile of rabbits injected with Se and As . In vitro evidence suggests the potential for the formation of this Se-As conjugate using glutathione (GS) complex (GS2AsSe) in the liver which is excreted into bile . Biliary excretion of As by this pathway would likely reduce the amount of As excreted in urine. However the existence of this conjugate in humans remains unknown. In addition, a study of rat kidney cells found that As and Se are concentrated and precipitated in the lysosomes of renal cells, forming an insoluble selenide (As2Se) that is eventually eliminated in the urine . This could be another potential As removal pathway.
A recent cross-sectional study in adults in Araihazar, Bangladesh found that plasma Se was inversely associated with urinary and blood As concentrations, and genomic DNA methylation . Consistent with this finding a case-cohort study conducted at the same study site found that participants with higher blood Se concentrations had significantly lower urinary As concentrations. In addition, it was found that those with blood Se below average were consistently at a greater risk of skin lesions associated with their As exposure . In contrast, a study in West Bengal found no difference in the blood Se concentration in those affected by skin lesion verses controls, however the As exposure of neither group was well characterized .
A recent animal study found that dietary organselenium was effective in preventing As from entering the peripheral tissue of mice that ingested arsenite in drinking water . A second animal study found that co-administration of sodium arsenite and selenite had a protective effect on liver enzyme activity, thiobarbituric acid reactive substances levels, as well on glutathione peroxidase and glutathione-S-transferase in comparison to As treated animals . These animal studies provide promising evidence for the role of Se in reducing As induced oxidative stress and the body burden of As.
A small clinical trial in Bangladesh has shown suggestive evidence that vitamin E and Se can slightly improve As induced skin lesions . There has only been one small study published to date evaluating the impact of daily supplementation of Se on blood As concentrations in humans. However this study conducted in Inner Mongolia combined a Se supplementation trial with an “As free” drinking water intervention making it difficult to determine the actual effect of the supplementation component .
The current study is the first evaluation of the relationship between As and Se in a pediatric population. The primary objective of this study is to test the hypothesis that blood Se is inversely associated with blood and urinary As concentrations in children and adults living in an As contaminated area of Bangladesh.