potassium-perchlorate and Body-Weight

The increasing pollution of aquatic habitats with anthropogenic compounds has led to various test strategies to detect hazardous chemicals. However, information on effects of pollutants in the thyroid system in fish, which is essential for growth, development and parts of reproduction, is still scarce. Other vertebrate groups such as amphibians or mammals are well-studied; so the need for further knowledge especially in fish as a favored vertebrate model test organism is evident. Modified early life-stage tests were carried out with zebrafish exposed to the known thyroid inhibitor potassium perchlorate (0, 62.5, 125, 250, 500 and 5000 μg/L) to identify adverse effects on the hypothalamic-pituitary-thyroid axis. Especially higher perchlorate concentrations led to conspicuous alterations in thyroidal tissue architecture and to effects in the pituitary. In the thyroid, severe hyperplasia at concentrations ≥ 500 μg/L together with an increase in follicle number could be detected. The most sensitive endpoint was the colloid, which showed alterations at ≥ 250 μg/L. The tinctorial properties and the texture of the colloid changed dramatically. Interestingly, effects on epithelial cell height were minor. The pituitary revealed significant proliferations of TSH-producing cells resulting in alterations in the ratio of adeno- to neurohypophysis. The liver as the main site of T4 deiodination showed severe glycogen depletion at concentrations ≥ 250 μg/L. In summary, the thyroid system in zebrafish showed effects by perchlorate from concentrations ≥ 250 μg/L, thus documenting a high sensitivity of the zebrafish thyroid gland for goitrogens. In the future, such distinct alterations could lead to a better understanding and identification of potential thyroid-disrupting chemicals.

Topics: Animals; Antithyroid Agents; Body Constitution; Body Size; Body Weight; Cell Proliferation; Gonads; Liver; Perchlorates; Pituitary Gland; Potassium Compounds; Thyroid Gland; Thyroxine; Water Pollutants, Chemical; Zebrafish

Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC-MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple parallel-occurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cognitive dysfunctions.

Topics: Animals; Body Weight; Cerebellum; Cluster Analysis; Disease Models, Animal; Gas Chromatography-Mass Spectrometry; Hypothyroidism; Male; Metabolic Networks and Pathways; Metabolome; Metabolomics; Mice; Mice, Inbred BALB C; Microarray Analysis; Perchlorates; Potassium Compounds; Principal Component Analysis; Reproducibility of Results

Larval sea lampreys (Petromyzon marinus) measuring 100-119 mm in length were exposed to thyroxine (T4; 10 mg liter-1) or 3,5,3'-triiodothyronine (T3; 1 mg liter-1) in the presence and absence of the goitrogen potassium perchlorate (KClO4; 0.01%), for 4-24 weeks. Every 4 weeks, treated and untreated (control) groups of sea lampreys were examined for external signs of metamorphosis and serum was assayed for T4 and T3 concentrations. Precocious metamorphosis was observed following 8, 12, and 24 weeks of KClO4 treatment; however, metamorphosis was not observed in any control, or T4-, T3-, T4+KClO4-, and T3+KClO4-treated larvae. In addition, serum T4 and T3 concentrations were 62 and 72% lower in KClO4-treated individuals than in control animals, respectively. Treatment with exogenous thyroid hormones (TH), in the presence or absence of KClO4, resulted in serum T4 concentrations which were significantly greater (1.2- to 58-fold) than those of the controls in all sampling periods except one, but serum T3 concentrations were not significantly elevated in more than 50% of the cases. TH+KClO4 treatments produced serum T3 concentrations which were significantly greater than those of KClO4-treated animals and never less than those of controls. These data indicate that larval sea lampreys have a tremendous capacity to take up and store exogenous T4 in their serum, but the uptake and/or serum storage of T3 appears to be stringently regulated. Also, the absence of both metamorphosis and a decline in serum TH concentrations in TH+KClO4-treated animals suggests that a decline in serum TH concentrations may be an essential factor contributing to the induction of metamorphosis by KClO4.

Topics: Animals; Body Weight; Lampreys; Larva; Metamorphosis, Biological; Perchlorates; Potassium Compounds; Radioimmunoassay; Thyroxine; Time Factors; Triiodothyronine

The effect of 1000 ppm potassium perchlorate (KClO4), 1000 ppm potassium iodide (KI) or 1000 ppm propylthiouracil (PTU) in the diet on the development of thyroid tumors was studied histologically and biochemically in Wistar rats given a single ip injection of 280 mg of N-bis(2-hydroxypropyl)nitrosamine (DHPN) per 100 g body weight. Basal diet containing 100 ppm KClO4, 1000 ppm KI or 1000 ppm PTU was given for 19 weeks from week 2 to week 20. The incidence of thyroid adenomas at the end of week 20 of the experiment was 100% (20/20) in rats treated with DHPN followed by KClO4, 85% (17/20) in rats given DHPN followed by KI, 95% (19/20) in rats given DHPN followed by PTU, and 5% (1/20) in rats given DHPN alone. The incidence of thyroid cancers was 100% (20/20) in rats treated with DHPN followed by KClO4, 65% (13/20) in rats treated with DHPN followed by KI and 0% (0/20) in rats treated with DHPN followed by or not followed by PTU. Rats given KClO4, KI or PTU alone and untreated rats had no thyroid tumors. The mean values of TSH in serum were 2.94 +/- 0.79 ng/ml in rats treated with DHPN followed by KClO4, 9.40 +/- 16.0 ng/ml in rats treated with DHPN followed by KI and 60.94 +/- 20.60 ng/ml in rats treated with DHPN followed by PTU. It was confirmed that (1) KClO4, PTU and KI promote the development of thyroid tumor in rats treated with DHPN, (2) the promoting effect of KClO4 or KI is stronger than that of PTU and (3) the value of TSH in serum is not parallel to the promoting effect on the development of thyroid tumor.

Topics: Animals; Body Weight; Cocarcinogenesis; Male; Nitrosamines; Organ Size; Perchlorates; Potassium; Potassium Compounds; Potassium Iodide; Propylthiouracil; Radioimmunoassay; Rats; Rats, Inbred Strains; Thyroid Gland; Thyroid Neoplasms