sodium-perchlorate and Hypertrophy

Perchlorate inhibits iodide uptake by thyroid follicles and lowers thyroid hormone production. Although several effects of perchlorate on the thyroid system have been reported, the utility of these pathologies as markers of environmental perchlorate exposures has not been adequately assessed. The present study examined time-course and concentration-dependent effects of perchlorate on thyroid follicle hypertrophy, colloid depletion, and angiogenesis; alterations in whole-body thyroxine (T4) levels; and somatic growth and condition factor of subadult and adult zebrafish. Changes in the intensity of the colloidal T4 ring previously observed in zebrafish also were examined immunohistochemically. Three-month-old zebrafish were exposed to ammonium perchlorate at measured perchlorate concentrations of 0, 11, 90, 1,131, and 11,480 ppb for 12 weeks and allowed to recover in clean water for 12 weeks. At two weeks of exposure, the lowest-observed-effective concentrations (LOECs) of perchlorate that induced angiogenesis and depressed the intensity of colloidal T4 ring were 90 and 1,131 ppb, respectively; other parameters were not affected (whole-body T4 was not determined at this time). At 12 weeks of exposure, LOECs for colloid depletion, hypertrophy, angiogenesis, and colloidal T4 ring were 11,480, 1,131, 90, and 11 ppb, respectively. All changes were reversible, but residual effects on angiogenesis and colloidal T4 ring intensity were still present after 12 weeks of recovery (LOEC, 11,480 ppb). Whole-body T4 concentration, body growth (length and weight), and condition factor were not affected by perchlorate. The sensitivity and longevity of changes in colloidal T4 ring intensity and angiogenesis suggest their usefulness as novel markers of perchlorate exposure. The 12-week LOEC for colloidal T4 ring is the lowest reported for any perchlorate biomarker in aquatic vertebrates.

Topics: Angiogenesis Inducing Agents; Animals; Biomarkers; Colloids; Environmental Exposure; Hypertrophy; Perchlorates; Sodium Compounds; Somatoform Disorders; Thyroid Gland; Thyroxine; Time Factors; Water Pollutants, Chemical; Zebrafish

We have studied the effects of propythiouracil (PTU) or perchlorate (CIO(4)(-)), given to the mothers' drink from the 15(th) day of pregnancy until the day of sacrifice, on thyroid function of suckling mice. Antihyroid drugs (PTU or CIO(4)(-)) provoked growth perturbations of young mice during studied ages from 6 to 18 days. A decrease of body weight was respectively as follows: 14 and 22% in 6 day-old mice; 16 and 23% in 10 day-old mice; 18 and 18% in 14 day-old mice; 19 and 11% in 18 day-old mice. We have noticed an hypertrophy of thyroid glands of pups and their mothers caused by an increase of pituitary TSH. Thyroid follicles presented the aspect of hypothyroid animals with an increase of follicular number and vascularisation. Structural modifications confirmed biochemical results. In fact thyroid iodine contents decreased strongly in young as follow: 40 and 43% in 6 day-old mice; 51 and 50% in 10 day-old mice; 66 and 84% in 14 day-old mice; 54 and 89% at 18 day-old mice and in their mothers (50, 37%; 59, 54%; 75, 65% and 85, 72%) respectively after PTU or CIO(4)(-) treatment. A decrease of iodine thyroid gland was accompanied by an important fall of free thyroid hormones levels (FT3 and FT4) in young and adult mice. A decrease of thyroid hormonemia could explain the pups' growth perturbations.

Topics: Aging; Animals; Antithyroid Agents; Female; Hypertrophy; Iodine; Lactation; Maternal-Fetal Exchange; Mice; Perchlorates; Pituitary Gland; Pregnancy; Propylthiouracil; Sodium Compounds; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

In a 46-week-experiment on 72 female mice the influence of peroral 1.2% sodium perchlorate application, total ionizing irradiation with 8 Gy on 5 consecutive days and their interaction on the pituitary-thyroid axis was studied by histological and stereological methods. It was observed that perchlorate alone caused long-term and strong hypothyroidism with hypertrophic and hyperplastic thyroid epithelial cells as well as pituitary thyrotropic cells. When only irradiation was used, no uniform changes in the structure and function of these cells could be detected. The interaction of perchlorate and irradiation showed similar effects as thyrostatics alone, with some exceptions; paradoxically, minor hyperplasia of thyrotropic as well as of parafollicular cells was observed. A high percentage of the follicular cell carcinoma was found after perchlorate application and after its combination with irradiation. No medullary carcinoma was found.

Topics: Animals; Epithelial Cells; Epithelium; Female; Gamma Rays; Hyperplasia; Hypertrophy; Mice; Mice, Inbred BALB C; Perchlorates; Pituitary Gland; Pituitary Gland, Anterior; Reference Values; Sodium Compounds; Thyroid Gland