Radioactive iodide ( 131I ?) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish 131I ? urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered 131I ? and 3 hours later dosed with either saline, 30 mg/kg of NH 4ClO 4 or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH 4ClO 4 treated animals excreted significantly more 131I ? compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T 4) was administered daily over a 3 day period. During the first 6–12 hour after 131I ? dosing, rats administered NH 4ClO 4 excreted significantly more 131I ? than the other treatment groups. T 4 treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after 131I ? administration. We speculate that the T 4 treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to 131I ? compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland.
References
[1]
National Committee For Responsive Philanthropy (NCRP). Protection of the Thyroid Gland in the Event of Release of Radioiodine; Report No. 055; NCRP: Bethesda, MD, USA, 1977; p. 65.
[2]
Becker, D.V.; Braverman, L.E.; Dunn, J.T.; Gaitan, E.; Gorman, C.; Maxon, H.; Schneider, A.B.; Van Middlesworth, L.; Wolff, J. The use of iodine as a thyroidal blocking agent in the event of a reactor accident. Report of the environmental hazards committee of the american thyroid association. JAMA 1984, 252, 659–661.
[3]
National Apprenticeship Service (NAS). Distribution and Administration of Potassium Iodide in the Event of A Nuclear Incident; The National Academies Press: Washington, DC, USA, 2004; p. 248.
[4]
Food and Drug Administration (FDA). Radiation Emergencies. Available online: http://www.fda.gov/Drugs/EmergencyPreparedness/BioterrorismandDrugPreparedness/ucm063807.htm (accessed on 7 November 2011).
[5]
Halmi, N.S.; Stuelke, R.G.; Schnell, M.D. Radioiodide in the thyroid and in other organs of rats treated with large doses of perchlorate. Endocrinology 1956, 58, 634–650, doi:10.1210/endo-58-5-634.
[6]
Schonbaum, E.; Sellers, E.A.; Gill, M.J. Some effects of perchlorate on the distribution of 131-iodide. Acta Endocrinol. (Copenhagen) 1965, 50, 195–201.
[7]
Ullberg, S.; Ewaldsson, B. Distribution of radio-iodine studied by whole-body autoradiography. Acta Radiol. Ther. Phys. Biol. 1964, 2, 24–32.
[8]
Anbar, M.; Guttmann, S.; Lewitus, Z. The mode of action of perchlorate ions on the iodine uptake of the thyroid gland. Int. J. Appl. Radiat. Isot. 1959, 7, 87–96, doi:10.1016/0020-708X(59)90153-X.
[9]
Goldman, S.J.; Stanbury, J.B. The metabolism of perchlorate in the rat. Endocrinology 1973, 92, 1536–1538, doi:10.1210/endo-92-5-1536.
[10]
Wolff, J. Perchlorate and the thyroid gland. Pharmacol. Rev. 1998, 50, 89–105.
[11]
Tran, N.; Valentin-Blasini, L.; Blount, B.C.; McCuistion, C.G.; Fenton, M.S.; Gin, E.; Salem, A.; Hershman, J.M. Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells. Am. J. Physiol. Endocrinol. Metab. 2008, 294, E802–E806, doi:10.1152/ajpendo.00013.2008.
[12]
Attanasio, R.; Scinicariello, F.; Blount, B.C.; Valentin-Blasini, L.; Rogers, K.A.; Nguyen, D.C.; Murray, H.E. Pendrin mediates uptake of perchlorate in a mammalian in vitro system. Chemosphere 2011, 84, 1484–1488, doi:10.1016/j.chemosphere.2011.04.038.
[13]
Krevans, J.R.; Asper, S.P., Jr.; Rienhoff, W.F., Jr. Fatal aplastic anemia following use of potassium perchlorate in thyrotoxicosis. JAMA 1962, 181, 162–164.
[14]
Trotter, W.R. The relative toxicity of antithyroid drugs. J. New Drugs 1962, 2, 333–343.
[15]
Harris, C.A.; Fisher, J.W.; Rollor, E.A., 3rd.; Ferguson, D.C.; Blount, B.C.; Valentin-Blasini, L.; Taylor, M.A.; Dallas, C.E. Evaluation of potassium iodide (KI) and ammonium perchlorate (Nh4ClO4) to ameliorate 131I? exposure in the rat. J. Toxicol. Environ. Health 2009, 72, 909–914.
[16]
Fisher, J.; Todd, P.; Mattie, D.; Godfrey, D.; Narayanan, L.; Yu, K. Preliminary development of a physiological model for perchlorate in the adult male rat: A framework for further studies. Drug Chem. Toxicol. 2000, 23, 243–258, doi:10.1081/DCT-100100113.
[17]
Yu, K.O.; Narayanan, L.; Mattie, D.R.; Godfrey, R.J.; Todd, P.N.; Sterner, T.R.; Mahle, D.A.; Lumpkin, M.H.; Fisher, J.W. The pharmacokinetics of perchlorate and its effect on the hypothalamus-pituitary-thyroid axis in the male rat. Toxicol. Appl. Pharmacol. 2002, 182, 148–159, doi:10.1006/taap.2002.9432.
[18]
Capen, C.C. Mechanistic data and risk assessment of selected toxic end points of the thyroid gland. Toxicol. Pathol. 1997, 25, 39–48, doi:10.1177/019262339702500109.
[19]
Connors, J.M.; Hedge, G.A. Feedback regulation of thyrotropin by thyroxine under physiological conditions. Am. J. Physiol. 1981, 240, E308–E313.
[20]
Larsen, P.R.; Frumess, R.D. Comparison of the biological effects of thyroxine and triiodothyronine in the rat. Endocrinology 1977, 100, 980–988, doi:10.1210/endo-100-4-980.
[21]
Dratman, M.B.; Crutchfield, F.L.; Gordon, J.T.; Jennings, A.S. Iodothyronine homeostasis in rat brain during hypo- and hyperthyroidism. Am. J. Physiol. 1983, 245, E185–E193.
[22]
Amitai, Y.; Winston, G.; Sack, J.; Wasser, J.; Lewis, M.; Blount, B.C.; Valentin-Blasini, L.; Fisher, N.; Israeli, A.; Leventhal, A. Gestational exposure to high perchlorate concentrations in drinking water and neonatal thyroxine levels. Thyroid 2007, 17, 843–850.
[23]
Valentin-Blasini, L.; Blount, B.C.; Delinsky, A. Quantification of iodide and sodium-iodide symporter inhibitors in human urine using ion chromatography tandem mass spectrometry. J. Chromatogr. 1155, 40–46.
[24]
Wolff, J. Physiological aspects of iodide excess in relation to radiation protection. J. Mol. Med. 1980, 4, 151–165.
[25]
Zanzonico, P.B.; Becker, D.V. Effects of time of administration and dietary iodine levels on potassium iodide (KI) blockade of thyroid irradiation by 131I from radioactive fallout. Health Phys. 2000, 78, 660–667, doi:10.1097/00004032-200006000-00008.
[26]
Sinadinovic, J.P.; Jovanovic, M. Effect of perchlorate and stabile iodide on the elimination of radioactive iodine (I 131) from the body. Glas Srp. Akad. Nauka Med. 1971, 23, 29–36.