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Title: Impaired arsenic metabolism in children during weaning

Abstract

Background: Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a susceptibility factor for a range of arsenic-related health effects, but there is no data on the importance of arsenic metabolism for effects on child development. Aim: To elucidate the development of arsenic metabolism in early childhood. Methods: We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA), the metabolites of iAs, in spot urine samples of 2400 children at 18 months of age. The children were born to women participating in a population-based longitudinal study of arsenic effects on pregnancy outcomes and child development, carried out in Matlab, a rural area in Bangladesh with a wide range of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in relation to age, sex, anthropometry, socio-economic status and arsenic exposure. Results: Arsenic concentrations in child urine (median 34 {mu}g/L, range 2.4-940 {mu}g/L), adjusted to average specific gravity of 1.009 g/mL, were considerably higher than that measured at 3 months of age, but lower than that in maternal urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which implies a marked change in metabolite pattern since infancy. In particular, there was a marked increase in urinary %MA, whichmore » has been associated with increased risk of health effects. Conclusion: The arsenic metabolite pattern in urine of children at 18 months of age in rural Bangladesh indicates a marked decrease in arsenic methylation efficiency during weaning.« less

Authors:
 [1];  [2]; ; ;  [1];  [3]
  1. Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm (Sweden)
  2. ICDDR-B: International Centre for Diarrhoeal Disease Research (Bangladesh)
  3. Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm (Sweden), E-mail: marie.vahter@ki.se
Publication Date:
OSTI Identifier:
21272645
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 239; Journal Issue: 2; Conference: Valencia Spain arsenic meeting: From nature to humans, Valencia (Spain), 21-23 May 2008; Other Information: DOI: 10.1016/j.taap.2008.12.019; PII: S0041-008X(08)00530-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARSENIC; CHILDREN; DENSITY; DRINKING WATER; METABOLISM; METABOLITES; METHYLATION; RURAL AREAS; URINE

Citation Formats

Faengstroem, Britta, Hamadani, Jena, Nermell, Barbro, Grander, Margaretha, Palm, Brita, and Vahter, Marie. Impaired arsenic metabolism in children during weaning. United States: N. p., 2009. Web. doi:10.1016/j.taap.2008.12.019.
Faengstroem, Britta, Hamadani, Jena, Nermell, Barbro, Grander, Margaretha, Palm, Brita, & Vahter, Marie. Impaired arsenic metabolism in children during weaning. United States. doi:10.1016/j.taap.2008.12.019.
Faengstroem, Britta, Hamadani, Jena, Nermell, Barbro, Grander, Margaretha, Palm, Brita, and Vahter, Marie. 2009. "Impaired arsenic metabolism in children during weaning". United States. doi:10.1016/j.taap.2008.12.019.
@article{osti_21272645,
title = {Impaired arsenic metabolism in children during weaning},
author = {Faengstroem, Britta and Hamadani, Jena and Nermell, Barbro and Grander, Margaretha and Palm, Brita and Vahter, Marie},
abstractNote = {Background: Methylation of inorganic arsenic (iAs) via one-carbon metabolism is a susceptibility factor for a range of arsenic-related health effects, but there is no data on the importance of arsenic metabolism for effects on child development. Aim: To elucidate the development of arsenic metabolism in early childhood. Methods: We measured iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA), the metabolites of iAs, in spot urine samples of 2400 children at 18 months of age. The children were born to women participating in a population-based longitudinal study of arsenic effects on pregnancy outcomes and child development, carried out in Matlab, a rural area in Bangladesh with a wide range of arsenic concentrations in drinking water. Arsenic metabolism was evaluated in relation to age, sex, anthropometry, socio-economic status and arsenic exposure. Results: Arsenic concentrations in child urine (median 34 {mu}g/L, range 2.4-940 {mu}g/L), adjusted to average specific gravity of 1.009 g/mL, were considerably higher than that measured at 3 months of age, but lower than that in maternal urine. Child urine contained on average 12% iAs, 9.4% MA and 78% DMA, which implies a marked change in metabolite pattern since infancy. In particular, there was a marked increase in urinary %MA, which has been associated with increased risk of health effects. Conclusion: The arsenic metabolite pattern in urine of children at 18 months of age in rural Bangladesh indicates a marked decrease in arsenic methylation efficiency during weaning.},
doi = {10.1016/j.taap.2008.12.019},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 239,
place = {United States},
year = 2009,
month = 9
}
  • Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potentialmore » and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant potential or both.« less
  • This study tested the hypothesis that the initiating mechanism is a major determinant of the response to calcium (Ca) accumulation in myocardium. Cultured neonatal rat ventriculocytes were exposed to Na+, K+ pump inhibition with 1 mM ouabain and metabolic inhibition with 20 mM 2-deoxy-D-glucose and 1 mM cyanide (DOG-CN) for up to 2 h. Microspectrofluorometry of myocytes loaded with fura-2 showed that ouabain resulted in a relatively rapid increase in (Ca2+)i up to 2-3 microM (two to threefold above peak systolic level) and that DOG-CN produced an initial decrease and then a relatively slow increase in (Ca2+)i up to peakmore » systolic level. Electron probe x-ray microanalysis (EPMA) showed prominent increases in Na and Ca and decreases in K and Mg in cytoplasm and mitochondria with both interventions, although the increases in Ca were greater with ouabain than DOG-CN. ATP was reduced by 58% after 1 and 2 h of ouabain and by 70 and 90% after 1 and 2 h of DOG-CN, respectively. Thus, ouabain produced greater calcium accumulation and less ATP reduction than DOG-CN. Upon return to normal medium for 30 min, myocytes showed recovery of most electrolyte alterations and resumption of normal Ca2+ transients after 1 h exposure to either ouabain or DOG-CN; however, recovery was less after 2 h of either treatment, with elevated (Ca2+)i maintained in many myocytes. We conclude that the severity of myocyte injury is influenced by the magnitude and duration of both ATP reduction and calcium accumulation.« less
  • The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations withmore » other biomarkers of arsenic exposure, including arsenic accumulation in nails (r = 0.56, P < 0.001) and arsenic concentration in urine (r = 0.50, P < 0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (∼ 4-fold, P < 0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (∼ 3-fold, P < 0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. - Highlights: • The effects of arsenic exposure in utero and through early childhood were studied. • Arsenic-exposed children had a reduction in arsenic methylation capacity. • Exposed children had more DNA damage, observed as elevated salivary 8-OHdG. • Lower salivary hOGG1 in exposed children indicated impairment of 8-OHdG repair. • Salivary and urinary 8-OHdG levels were discordant.« less
  • Zinc and copper absorption from five infant cereal products mixed with water, human milk, or cow's milk was measured using an in vivo absorption model (rat pup) involving gastric intubation of extrinsically radiolabeled diets. Whole-body copper 64 uptake, nine hours after intubation, ranged from 14% to 31% of the dose given for the different cereal combinations. The resultant bioavailability of copper from human milk-cereal combinations (23% to 26%) was significantly lower than that from human milk alone (38%). Whole-body zinc 65 uptake, nine hours after intubation, ranged from 13% to 54% of the dose given for the different cereal combinations.more » These values were significantly lower than the whole-body zinc 65 uptake from milk alone (61%). Zinc availability was lower (13% to 25%) from dry cereal combinations that contained phytic acid (oatmeal and high-protein varieties) compared with the ready-to-serve cereal-fruit combinations (24% to 54%). The highest zinc uptake (37% to 54%) was from rice-fruit combinations that do not contain phytic acid. We estimated the amounts of zinc and copper that would be absorbed from these cereal products and speculated on the potential impact of these foods on the weaning infant's zinc and copper nutriture. Depending on the feeding practices employed during the weaning period, it is apparent that infant cereals may compromise utilization of zinc and copper from milk diets during weaning.« less
  • Northern elephant seals (NES) (Mirounga angustirostris) from the Año Nuevo State Reserve (CA, USA) were longitudinally sampled during the post-weaning fast in order to study the mobilisation and redistribution of various classes of persistent organic pollutants (POPs), such as polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p′-DDE) and hexachlorobenzene (HCB) between blubber and blood. Inner and outer blubber layers were analysed separately. Organohalogenated compounds were detected in all blubber samples in the decreasing order of their concentrations: p,p′-DDE>PCBs⪢HCB>PBDEs. The concentrations of all studied compounds were homogeneously distributed in the blubber layer at early fast, since the concentrations of POPsmore » were statistically not different in the inner and outer layers. With the progression of the fast, the concentrations of PBDEs, PCBs and p,p′-DDE increased more sharply in inner blubber than in outer blubber. As a result, their levels became significantly higher in inner blubber as compared to outer blubber at late fast. The rise of pollutant concentrations in blubber might result from a less efficient mobilisation than triglycerides and/or a reuptake by adipocytes of some of the pollutants released into the circulation. The mobilisation of pollutants from blubber was higher at late fast. An increase of pollutant concentrations was observed in serum between early and late fast. Lower halogenated congeners (i.e. tetra-CBs) were present in higher proportions in serum, whereas the higher halogenated congeners (i.e. hepta-CBs) were mainly found in the inner and outer blubber layers. The transfer ratios of both PBDEs and PCBs from inner blubber to serum decreased with the number of chlorine and bromine atoms. In addition, the distribution of both types of compounds between serum and blubber was strongly influenced by their lipophilic character (log K{sub ow} values), with more lipophilic compounds being less efficiently released from blubber to serum. - Highlights: • The POP concentrations were evenly distributed in blubber layers at early fast. • The POP concentrations were higher in inner than in outer blubber at late fast. • The POP concentrations increased in blubber and serum over the fast. • POPs were less efficiently mobilised from blubber than triglycerides. • The mobilisation of POPs from blubber was influenced by their lipophilic character.« less