Arsenic alters monocyte superoxide anion and nitric oxide production in environmentally exposed children

Arsenic (As) exposure has been associated with alterations in the immune system, studies in experimental models and adults have shown that these effects involve macrophage function; however, limited information is available on what type of effects could be induced in children. The aim of this study was to evaluate effects of As exposure, through the association of inorganic As (iAs) and its metabolites [monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] with basal levels of nitric oxide (NO⁻) and superoxide anion (O₂⁻), in peripheral blood mononuclear cells (PBMC) and monocytes, and NO⁻ and O₂⁻ produced by activated monocytes. Hence, a cross-sectional study was conducted in 87 children (6-10 years old) who had been environmentally exposed to As through drinking water. Levels of urinary As species (iAs, MMA and DMA) were determined by hydride generation atomic absorption spectrometry, total As (tAs) represents the sum of iAs and its species; tAs urine levels ranged from 12.3 to 1411 μg/g creatinine. Using multiple linear regression models, iAs presented a positive and statistical association with basal NO⁻ in PBMC (β = 0.0048, p = 0.049) and monocytes (β = 0.0044, p = 0.044), while basal O₂⁻ had a significant positive association with DMA (β = 0.0025, p = 0.046). In activated monocytes, O₂⁻ showed a statistical and positive association with iAs (β = 0.0108, p = 0.023), MMA (β = 0.0066, p = 0.022), DMA (β = 0.0018, p = 0.015), and tAs (β = 0.0013, p = 0.015). We conclude that As exposure in the studied children was positively associated with basal levels of NO⁻ and O₂⁻ in PBMC and monocytes, suggesting that As induces oxidative stress in circulating blood cells. Additionally, this study showed a positive association of O₂⁻ production with iAs and its metabolites in stimulated monocytes, supporting previous data that suggests that these cells, and particularly the O₂⁻ activation pathway, are relevant targets for As toxicity.