title: The effects of gestational arsenic exposure and dietary selenium deficiency on selenium and selenoenzymes in maternal and fetal tissues in mice.
abstract: Although toxicological and metabolic interactions of arsenic (As) and selenium (Se) have been suggested by epidemiolgical literatures, the past experimental studies mostly focused on acute, high-dose interaction, leaving the long-term, low-dose interaction unexplored. In the present study pregnant mice, fed either Se-deficient or adequate (0 or 5 micromol Se/kg diet, respectively) diet, were given oral gavage of sodium arsenite (0 or 58 micromol/kg per day; chosen as less than half of the fetotoxic dose in this protocol) from gestational day (GD) 7-16. The levels of As and Se as well as five selenoenzymes (glutathione peroxidase (GPx), thioredoxin reductase (TRxR), and type-I, -II and -III iodothyronine deiodinases (DI-I, -II and -III) were examined on GD17 in the tissues of dams and of fetus. The Se-deficient mice showed significantly enhanced accumulation of As compared to the Se-adequate mice in maternal liver (increased by 48%) and fetal brain (by 31%). Although no direct evidence of the enhanced toxicity in the Se-deficient group was obtained, the As exposure affected the levels of Se and selenoenzymes, an effect which was more discernible in Se-deficient group. Although most of theses changes were mild or moderate, the DI-II activity in Se-deficient fetal brain showed a drastic four-fold increase by As exposure, suggesting a possible disturbance of thyroid hormone environment in the fetus. These data suggested that apparently non-toxic, in utero dose of As, showed enhanced accumulation when combined with Se-deficiency and could affect the metabolism/kinetics of Se in fetal brain, which might result in developmental toxicity in mice.
authors.affiliation: Department of Public Health, Division of Environmental Medicine, Gunma University Graduate School of Medicine, 3-39-22, Maebashi City, Gunma 371-8510, Japan. kmiyazak@med.gunma-u.ac.jp
authors.forename: Kaori
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Chiho
authors.initials: C
authors.lastname: Watanabe
authors.forename: Kouki
authors.initials: K
authors.lastname: Mori
authors.forename: Katusmi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Ohtsuka
mesh_terms: D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004032:Diet; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D051379:Mice; D008813:Mice, Inbred ICR; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D012643:Selenium / Q000032:analysis / Q000172:deficiency*; D017670:Sodium Compounds / Q000633:toxicity*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D018053:Arsenites; D004791:Enzyme Inhibitors; D005979:Glutathione Peroxidase; D007453:Iodide Peroxidase; D012643:Selenium; D017670:Sodium Compounds; D013880:Thioredoxin-Disulfide Reductase; D014874:Water Pollutants, Chemical; D000097564:Iodothyronine Deiodinase Type II; C017947:sodium arsenite; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III