Acta Biologica Hungarica

, Volume 61, Issue 2, pp 145–157 | Cite as

Effect of Selenium on Hypothyroidism Induced by Methimazole (MMI) in Lactating Rats and Their Pups

  • Ibtissem Ben Amara
  • Hanen Bouaziz
  • Fadhel Guermazi
  • Najiba ZeghalEmail author


The present study was undertaken to assess the effect of selenium (Se) on hypothyroidism induced by methimazole (MMI) in lactating rats and their pups. Rats were randomly divided into four groups of six each: group I served as a negative control which received standard diet; group II received orally MMI (250 mg L−1); group III received both MMI (250 mg L−1, orally) and Se (0.5 mg/kg of diet); group IV served as a positive control and received Se (0.5 mg Na2 SeO3/kg of diet). Treatments were started from the 14th day of pregnancy until postnatal day 14. In the MMI-exposed group, the body weight of 14-day-old pups diminished compared to controls; besides, a hypertrophy of the thyroid glands was observed. Co-administration of Se through the diet restored these parameters to near normal values. In the MMI-treated group, thyroid iodine contents and plasma thyroid hormone levels significantly decreased, while plasma TSH levels increased in pups and their mothers. These biochemical modifications corresponded histologically to closed follicles, increased vascularity and a reduction in colloid volume. Co-treatment with Se ameliorated these parameters. We concluded that the supplementation of Se in diet had beneficial effects on hypothyroidism during a critical period of life.


Selenium Methimazole FT4 FT3 TSH adult rats nursing pups 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



The authors are indebted to Mrs Nabiha Mezghanni for her skillful technical assistance in radioimmunoassays. We also wish to extend our thanks to Mr Bejaoui Hafed, teacher of English at Sfax Faculty of Science, who has helped proofread and edit this paper. This work was supported by the DGRST grant (Appui à la Recherche Universitaire de Base ARUB 99/UR/08-73), Tunisia.


  1. 1.
    Aboul-Enein, H. Y., Al-Badr, A. A. (1979) Methimazole. In: Forey, K. (ed.), Analytical Profiles of Drug Substance. Academic Press, New York 18, pp. 351–371.Google Scholar
  2. 2.
    Aletrari, M., Kanari, P., Partassides, D., Loizou, E. (1998) Study of the british pharmacopeia method on methimazole (thiamazole) content in carbimazole tablets. J. Pharm. Biomed. Anal. 16, 785–792.PubMedGoogle Scholar
  3. 3.
    Ampong, B., Honda, H., Kogo, H. (2002) Effect of hypothyroidism on β-adrenoreceptor-mediated relaxation in the rat thoracic aortae: A time-dependent study. Vascul. Pharmacol. 38, 149–155.PubMedGoogle Scholar
  4. 4.
    Anan, Y., Ogra, Y., Somekawa, L., Suzuki, K. T. (2009) Effects of chemical species of selenium on maternal transfer during pregnancy and lactation. Life Sci. 84, 888–893.PubMedGoogle Scholar
  5. 5.
    Aragão, C. N., Souza, L. L., Cabanelas, A., Oliveira, K. J., Pazos-Moura, C. C. (2007) Effect of experimental hypo- and hyperthyroidism on serum adiponectin. Metab. Clin. Exper 56, 6–11.Google Scholar
  6. 6.
    Archimbaud, Y., Grillion, G., Poncy, J. L., Masse, R. (1992) 75Se transfer via placenta and milk, distribution and retention in fetal, young and adult rat. Radial Prot. Dosimetry 41, 147–151.Google Scholar
  7. 7.
    Bandyopadhyay, U., Biswas, K., Banerjee, R. K. (2002) Extrathyroidal actions of antithyroid thion-amides. Toxicol. Lett. 128, 117–127.PubMedGoogle Scholar
  8. 8.
    Beaufrère, B., Bresson, J. L., Briend, A., Ghisolfi, J., Goulet, O., Navarro, J., Putet, G., Ricour, C. Rieu, D., Turck, D., Vidailhet, M. (2000) La nutrition iodée chez l’enfant. Arch. Pediatr. 7, 66–74.PubMedGoogle Scholar
  9. 9.
    Beckett, C. J., Arthur, J. R. (1994) Hormone-nuclear receptor interactions in health and disease. The iodothyronine deiodinases and 5’-deiodination. Baillieres Clin. Endocrinol. Metab. 8, 285–304.PubMedGoogle Scholar
  10. 10.
    Ben Hamida, F., Soussia, L., Guermazi, F., Rebai, T., Zeghal, N. (2001) Effets de deux antithyroidïens (propyltiouracile et perchlorate) sur la fonction thyroidïenne de la souris en période d’allaitement. Ann. Endocrinol. 62, 446–453.Google Scholar
  11. 11.
    Bouaziz, H., Soussia, L., Guermazi, F., Zeghal, N. (2005) Fluoride-induced thyroid proliferative changes and their reversal in female mice and their pups. Fluoride 38, 185–192.Google Scholar
  12. 12.
    Carrasco, N. (1993) Iodide transport in the thyroid gland. Biochim. Biophys. Acta 154, 65–82.Google Scholar
  13. 13.
    Colzani, R. M., Alex, S., Fang, S. L., Stone, S., Braverman, L. E. (1999) Effects of iodine repletion on thyroid morphology in iodine and/or selenium deficient rat term fetuses, pups and mothers. Biochimie 81, 485–491.PubMedGoogle Scholar
  14. 14.
    Council of European Communities (1986) Council instructions about the protection of living animals used in scientific investigations. Official Journal of the European Communities (JO 86/609/CEE) L358, pp. 1–18.Google Scholar
  15. 15.
    Dorea, J. G. (2002) Iodine nutrition and breast feeding. J. Trace Elem. Med. Biol. 16, 207–220.PubMedGoogle Scholar
  16. 16.
    Dussault, J. H., Ruel, J. (1987) Thyroid hormones and brain development. Annu. Rev. Physiol. 49, 321–334.PubMedGoogle Scholar
  17. 17.
    Fetoui, H., Bouaziz, H., Mahjoubi-Samet, A., Soussia, L., Guermazi, F., Zeghal, N. (2006) Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups. Acta Biol. Hung. 57, 391–402.PubMedGoogle Scholar
  18. 18.
    Fishbeck, K. L., Rasmussen, K. M. (1987) Effect of repeated cycles on maternal nutritional status, lactational performance and litter growth in ad libitum-fed and chronically food-restricted rats. J. Nutr. 117, 1967–1975.Google Scholar
  19. 19.
    Gabe, M. (1968) Techniques histologiques. Masson & Cie, Paris.Google Scholar
  20. 20.
    Ghorbel, H., Fetoui, H., Mahjoubi, A., Guermazi, F., Zeghal, N. (2008) Thiocyanate effects on thyroid function of weaned mice. C R. Biol. 331, 262–271.PubMedGoogle Scholar
  21. 21.
    Golstein, J., Corvilain, B., Lamy, F., Paquer, D., Dumont, J. E. (1988) Effects of a selenium deficient diet on thyroid function of normal and perchlorate treated rats. Acta Endocrinol. 118, 495–502.PubMedGoogle Scholar
  22. 22.
    Hotz, C. S., Fitzpatrick, D. W., Trick, K. D., L’Abbé, M. R. (1997) Dietary iodine and selenium interact to affect thyroid hormone metabolism of rats. J. Nutr. 127, 1214–1218.PubMedGoogle Scholar
  23. 23.
    Köhrle, J. (1999) The trace element selenium and the thyroid gland. Biochimie 81, 527–533.PubMedGoogle Scholar
  24. 24.
    Koornstra, J. J., Kerstens, M. N., Hoving, J., Visscher, K. J., Schade, H. J., Gort, H. B. W., Leemhuis, M. P. (1999) Clinical and biochemical changes following 1311 therapy for hyperthyroidism in patients not pretreated with antithyroid drugs. Neth. J. Med 55, 215–221.PubMedGoogle Scholar
  25. 25.
    Mahjoubi-Samet, A., Fetoui, H., Soussia, L., Guermazi, F., Zeghal, N. (2005) Dimethoate effects on thyroid function in suckling rats. Ann. Endocrinol. 66, 96–104.Google Scholar
  26. 26.
    Mandel, S. J., Cooper, D. S. (2001) The use of antithyroid drugs in pregnancy and lactation. J. Clin Endocrinol. Metab. 86, 2354–2359.PubMedGoogle Scholar
  27. 27.
    Marchant, B., Alexander, W. D. (1972) The thyroid accumulation, oxidation and metabolic fate of 35 S-methimazole in the rat. Endocrinology 91, 747–756.PubMedGoogle Scholar
  28. 28.
    Marchant, B., Brownlie, B. E., Hart, D. M., Horton, P. W., Alexander, W. D. (1977) The placental transfer of propylthiouracil, methimazole and carbimazole. J. Clin. Endocrinol. Metab. 45, 1187–1193.PubMedGoogle Scholar
  29. 29.
    Miyazaki, K., Watanabe, C., Mori, K., Yoshida, K., Ohtsuka, R. (2005) The effects of gestational arsenic exposure and dietary selenium deficiency on selenium and selenoenzymes in maternal and fetal tissues in mice. Toxicology 208, 357–365.PubMedGoogle Scholar
  30. 30.
    Porter, T. E. (2005) Regulation of pituitary somatotroph differentiation by hormones of peripheral endocrine glands. Domest. Anim. Endocrinol. 29, 52–62.PubMedGoogle Scholar
  31. 31.
    Rock, M. J., Kincaid, R. L., Carstens, G. E. (2001) Effects of prenatal source and level of dietary selenium on passive immunity and thermometabolism of newborn lambs. Small Ruminant Res. 40, 129–138.Google Scholar
  32. 32.
    Rosebrough, R. W., Russell, B. A., McMurtry, J. P. (2006) Studies on doses of methimazole (MMI) and its administration regimen on broiler metabolism. Comp. Biochem. Rhys. A 143, 35–41.Google Scholar
  33. 33.
    Roy, G., Das, D., Mugesh, G. (2007) Bioinorganic chemistry aspects of the inhibition of thyroid hormone biosynthesis by anti-hyperthyroid drugs. Inorganica Chimica Acta 360, 303–316.Google Scholar
  34. 34.
    Sandell, E. B., Kolthoff I. M. (1937) Microdetermination of iodine by a catalytic method. Microchem. Acta 1, 9–25.Google Scholar
  35. 35.
    Schwartz, H. L., Ross, M. E., Oppenheimer, J. H. (1997) Lack of effect of thyroid hormone on late fetal rat brain development. Endocrinology 138, 3119–3124.PubMedGoogle Scholar
  36. 36.
    Smith, A. M., Picciano, M. F. (1986) Evidence for increased selenium requirement for the rat during pregnancy and lactation. J. Nutr. 116, 1068–1079.PubMedGoogle Scholar
  37. 37.
    Soussia, L., Ben Hamida, F., Guermazi, F., Zeghal, N. (2004) Induction et réversibilité d’action du thiocyanate sur la fonction thyroïdienne chez le rat en période d’allaitement. Ann. Endocrinol. 65, 451–458.Google Scholar
  38. 38.
    Tazebay, U. H., Wapnir, I. L., Levy, O., Dohan, O., Zuckier, L. S., Zhao, Q. H., Deng, H. F., Amenta, P. S., Fineberg, S., Pestell, R. G., Carrasco, N. (2000) The mammary gland iodide transporter is expressed during lactation and in breast cancer. Nat. Med. 6, 871–878.PubMedGoogle Scholar
  39. 39.
    Thiel, R., Fowkes, S. W. (2007) Down syndrome and thyroid dysfunction: Should nutritional support be the first-line treatment? Med Hypotheses 69, 809–815.PubMedGoogle Scholar
  40. 40.
    Van Doom, J., Roelfsema, F., Van Der Heide, D. (1983) The effects of propylthiouracil and methima-zole on the peripheral conversion of thyroxine to 3,5,3-triiodothyronine in athyreotic thyroxine-maintained rats. Acta. Endocrinol. 103, 509–520.Google Scholar
  41. 41.
    Zagrodzki, P., Szmigiel, H., Ratajczak, R., Szybinski, Z., Zachwieja, Z. (2000) The role of selenium in iodine metabolism in children with goiter. Environ. Health Perspect. 108, 67–71.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Zimmermann, M. B. (2008) Iodine requirements and the risks and benefits of correcting iodine deficiency in populations. J. Trace Elem. Med. Biol. 22, 81–92.Google Scholar

Copyright information

© Akadémiai Kiadó, Budapest 2010

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • Ibtissem Ben Amara
    • 1
  • Hanen Bouaziz
    • 1
  • Fadhel Guermazi
    • 2
  • Najiba Zeghal
    • 1
    Email author
  1. 1.Department of Life Sciences, Animal Physiology LaboratorySfax Faculty of ScienceSfaxTunisia
  2. 2.Nuclear Medicine ServiceCHU Habib Bourguiba of SfaxSfaxTunisia

Personalised recommendations