Propylthiouracil

About: Propylthiouracil is a research topic. Over the lifetime, 2181 publications have been published within this topic receiving 46996 citations. The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.

Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats

Abstract: The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

Preliminary validation of a short-term morphological assay to evaluate adverse effects on amphibian metamorphosis and thyroid function using Xenopus laevis.

Abstract: Short-term static-renewal studies were performed on Xenopus laevis embryos with 16 selected test materials from day 50 (stage 60) to day 64 (stage 66) (14-day test) to evaluate effects on tail resorption and thyroid function. Of the 16 test materials, nine were found to inhibit significantly the rate of tail resorption, four were found to stimulate metamorphosis and three had no appreciable effect on the rate of metamorphosis. In an effort to determine if the morphological effects observed were related to alteration in thyroid activity, measurement of triiodothyronine (T3) in the test organisms and coadministration studies using thyroxine (agonist) or propylthiouracil (antagonist) were performed based on the morphological response noted during tail resorption. Of the nine compounds found to inhibit the rate of tail resorption, six were found to reduce the levels of T3. In each case, the inhibitory response could be at least partially alleviated by the co-administration of thyroxine. Larvae exposed to the four stimulatory agents had somewhat elevated levels of T3 and were responsive to propylthiouracil antagonism. These results suggest that 12 of the 14 compounds tested in this study that altered the rate of tail resorption did so via the thyroid axis. Overall, the X. laevis model appeared to be a suitable system for evaluating the impact of environmental agents and chemical products on thyroid function.

Effects of Soyasaponins on Lipid Peroxidation through the Secretion of Thyroid Hormones

Abstract: We investigated how soyasaponins (SS), which had been isolated from soybeans (Glycine max Merrill, seeds), influenced lipid peroxidation. The in vivo reduction in hepatic lipid peroxidation in mice intraperitoneally injected with total soyasaponins (TSS) was comparable to that which has been observed for alpha-tocopherol (VE). However, TSS and its five main constituent saponins (I, II, III, A1, and A2) had a much weaker in vitro inhibitory effect on lipid peroxidation induced by NADPH in mouse liver microsomes than VE. Therefore, we were not able to explain the in vivo effect of SS on lipid peroxidation level through direct antioxidative effects. We also demonstrated that TSS increased the levels of serum thyroid hormones. The effect of serum thyroid hormones on in vitro lipid peroxidation was much stronger than that observed for VE. Furthermore, the effects of TSS on levels of serum thyroid hormones and LPO were markedly decreased by propylthiouracil, an antithyroid drug. These results indicate that the effects of SS on lipid peroxidation levels appear to be mediated through the secretion of thyroid hormones.

Effects of methylmercaptoimidazole (MMI), propylthiouracil (PTU), potassium perchlorate (KClO4) and potassium iodide (KI) on the serum concentrations of thyrotrophin (TSH) and thyroid hormones in the rat.

Abstract: Male Sprague-Dawley rats were given graded doses of methylmercaptoimidazole (MMI), propylthiouracil (PTU), KClO4 or KI in drinking water for 4 days, or the lowest effective dose of each drug for various times. The rats were sacrificed at 1--2 p.m. and serum T3, T4 and TSH concentrations were measured by radioimmunoassays. It was found that administration of 5 mg/l of MMI, 10 mg/l of PTU and 100 mg/l of KClO4 for 4--14 days induced a transient rise in serum TSH and a fall in serum T3 or T4 or in both. The effects of KI were not consistent. In another series of experiments, PTU (10 mg/l) was given in drinking water for 4 days, and then graded doses of T3 or T4 were given iv, or 100 ng of TRH was injected into a tail vein, or the animals were exposed to 4 degrees C for 30 min. The initial high TSH levels were further increased by TRH and cold and decreased by T3 and T4. The PTU-treated animals had goitres after 4 days. We infer that low doses, that is to say 10--100 times lower than previously described, of antithyroid drugs induce a hypothyroidism characterized by an increased TSH level and a decreased serum T3 or T4 level or both. A 4 days' treatment with PTU (40 mg/l in tap water) is a suitable tool for studying the effect of various conditions on TSH secretion.