Exposure to inorganic arsenic in pregnancy and metabolism-nutrition interaction

Abstract: Inorganic arsenic is metabolized by most mammals, including humans, via alternating reduction and oxidative methylation with S-adenosylmethionine as main methyl donor. Thus, it seems likely that it is influenced by the availability of methyl groups. The main arsenic metabolites excreted in human urine are monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), besides un-methylated inorganic arsenic (arsenate [As(V)] and arsenite [As(III)]). The aim of the present study was to investigate: arsenic exposure during pregnancy and arsenic metabolism in relation to nutritional status in people chronically exposed to inorganic arsenic via drinking water in Mablab, Bangladesh, an area with high-elevated concentrations of arsenic in tubewells. For assessment of arsenic exposure, total arsenic concentrations in urine and drinking water were determined by hydride generation atomic absorption spectrophotometry (HG-AAS). In order to assess methylation capacity, arsenic metabolites in urine were speciated by high performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). There was a considerable variation in urinary concentrations of arsenic (total range P 1,470 µg/L, adjusted to specific gravity 1.0 12 g/mL) measured in 3,426 pregnant women in about gestational week 8, with an overall median concentration of 80 µg/L. Similar concentrations were found in gestational week 30, indicating no trend of decreasing exposure, despite the initiated mitigation activities in the area. Arsenic exposure was negatively associated with socioeconomic groups and achieved educational level. We studied the effect of macro-nutritional status, assessed by body mass index (BMI) and urinary creatinine excretion, among 442 pregnant women in gestational week 9, and the effects of micro-nutritional status, assessed by serum folate, vitamin B12, zinc, and ferritin as well as urinary selenium, among 753 women in gestational week 14. The average proportions of iAs, MMA, and DMA in urine in gestational week 9 were 15%, 11 % and 74%, respectively, indicating efficient arsenic methylation in spite of the malnutrition (about one third of the women had BMI below 18.5 kg/m 2) . Also, we found that the metabolism of inorganic arsenic was only marginally influenced by micro- nutritional status, except for selenium and, probably, zinc. Urinary %MMA increased with increasing serum zinc and %DMA increased with increasing urinary selenium, indicating a role of both essential elements in arsenic methylation. However, the arsenic exposure level assessed by the urinary arsenic had the greatest impact on arsenic methylation among the studied factors. The further research will focus on changes in arsenic methylation during pregnancy and birth weight. Keywords: Arsenic, metabolism, methylation, women, pregnant, drinking water