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PAVELKA, Babicky, Vobecky
Biological half-life of bromide in the rat depends primarily on the magnitude of sodium intake.Pavelka S, Babicky A, Vobecky M. Physiol Res. 2005;54(6):639-44.
"The parallel course of the excretion rates of bromide and sodium ions was demonstrated in adult male and female rats administered simultaneously with potassium 82Br-bromide and 24Na-sodium chloride. The animals were exposed to various intakes of sodium ions accompanied with five different anions: Br-, Cl-, HCO3-, ClO4-, and SCN-. Regardless of the anion accompanying the sodium ion, the excretion rates of 82Br- and 24Na+ ions were proportional to the magnitude of sodium intake in the animals. Hence, we have proved our hypothesis that the biological half-life of bromide depends on the magnitude of sodium intake rather than on the intake of chloride."
Biological half-lives of bromide and sodium in the rat are connected and dependent on the physiological state.Babicky A, Pavelka S, Vobecky M. Biol Trace Elem Res. 2005 Jan;103(1):49-58. [abstract only]
"The parallel course of the excretion rates of sodium and bromide ions was demonstrated in adult male rats administered simultaneously with 24Na-sodium chloride and 82Br-bromide. These excretion rates were inversely proportional to the magnitude of sodium intake in the animals. The biological half-life of bromide, as a substitute for sodium or chloride, was investigated with the aid of the radionuclide 82Br in animals situated in very different physiological states (i.e., in lactating and nonlactating female rats as well as in young rats of varying ages [2, 4, 6, and 10 wk of age]). The 82Br radioactivity retained in mothers and in whole litters was measured in vivo at appropriate time intervals (up to 240 h) after the application of 82Br-bromide to the mothers. The time-course of the changes in the 82Br radioactivity of the young was calculated as the difference between the rate of 82Br intake in the mother's milk and the 82Br excretion through the kidneys into the urine. The rate of 82Br excretion through the kidneys of the dam could be calculated also. Nonweaned young rats (12 d) had the highest half-life (269 h) and lactating dams had the lowest (44 h). The determined values demonstrated that nonweaned young apparently conserve sodium, because of its relatively low concentration in mother's milk, whereas lactating dams, because of their large food intake, waste sodium."
Metabolism of bromide and its interference with the metabolism of iodine.Pavelka S. Physiol Res. 2004;53 Suppl 1:S81-90. Review.
"The present knowledge about the metabolism of bromide with respect to its goitrogenic effects, including some conclusions drawn from our recent research on this subject, is reviewed. Firstly, the biological behavior of bromide ion is compared with that of chloride and iodide. Secondly, the details about distribution and kinetics of bromide ions in the body and in 15 different organs and tissues of the rat are given. Significant correlation between the values of the steady-state concentration of bromide in the respective tissue and of the corresponding biological half-life was found in most tissues examined. A remarkably high concentration of radiobromide was found in the skin, which represents, due to its large mass, the most abundant depot of bromide in the body of the rat. Thirdly, the effects of excessive bromide on the rat thyroid are summarized, along with the interference of exogenous bromide with the whole-body metabolism of iodine. It is suggested that high levels of bromide in the organism of experimental animals can influence their iodine metabolism in two parallel ways: by a decrease in iodide accumulation in the thyroid and skin (and in the mammary glands in lactating dams), and by a rise in iodide excretion by kidneys. By accelerating the renal excretion of iodide, excessive bromide can also influence the pool of exchangeable iodide in the thyroid. Finally, our recent results concerning the influence of high bromide intake in the lactating rat dam on iodine and bromide transfer to the suckling, and the impact of seriously decreased iodine content and increased bromide concentration in mother's milk on the young are discussed. We must state, however, that the virtue of the toxic effects of excessive bromide on the thyroid gland and its interference with the biosynthesis of thyroid hormones, as well as the exact mechanism of bromide interference with postnatal developmental processes remains to be elucidated."
The effect of bromide on the ultrastructure of rat thyrocytes.Velicky J, Titlbach M, Lojda Z, Duskova J, Vobecky M, Raska I. Ann Anat. 2004 Jun;186(3):209-16. [abstract only]
"Electron microscopic examination of thyroid tissue following administration of bromide to rats showed marked hypertrophy and hyperplasia in the thyrocytes, microfollicular rearrangement and lowered volume of colloid. The luminal surface of the thyrocytes showed increased size and number of microvilli, often filling the microlumen. Most of the nuclei were irregular in shape with unusual incisions and a higher density of chromatin. Proliferation of ER was seen with significantly dilated cisterns containing low electron density material. The Golgi complex was well developed and larger in rats receiving 10 mg Br/l drinking water (16 days) and 100 mg Br/l (16 and 66 days) than in control rats. Granules and small spherical structures (50-100 nm) appeared in the subapical part of the cytoplasm and their number increased in animals after administration of 50 mg Br-/l (16 and 66 days), 100 mg Br-/l (16 and 66 days), 200 and 400 mg Br-/l (133 days). In contrast, their number was reduced in thyrocytes of rats treated with 100 mg Br/l (16, 66 and 133 days). Colloid droplets were only rarely found. There was no significant change in the amount of mitochondria, secondary lysosomes including phagolysosomes. Some thyrocytes showed signs of necrosis in animals following administration of 10 mg Br/l (16 days, 100 and 400 mg Br/l, 133 days). Clusters of thyrocytes with spongy cytoplasm and bizarre shaped nuclei were found in groups treated with 100 mg Br/l, and 400 mg Br-/l (133 days). These changes, with previously published light microscopical, radioanalytical and biochemical findings, confirm the goitrogenic effect of bromide."
Impact of high bromide intake in the rat dam on iodine transfer to the sucklings.Pavelka S, Babicky A, Lener J, Vobecky M. Food Chem Toxicol. 2002 Jul;40(7):1041-5. [abstract only]
"A significant impact of high bromide levels in the organism of the mother on iodine transfer to the sucklings was established in experiments with female Wistar rats. The observed decrease in iodine transfer to the young through mothers' milk and/or an increase in the bromide concentration in the milk, caused a decrease in body weight of the pups. Enhanced bromide levels also adversely affected the thyroid gland of the young. High bromide intake in the lactating dams caused a decrease in iodide accumulation in the mammary glands, and also an increase in iodide elimination through the kidneys."
High bromide intake affects the accumulation of iodide in the rat thyroid and skin.Pavelka S, Babicky A, Vobecky M, Lener J. Biol Trace Elem Res. 2001 Summer;82(1-3):133-42. [abstract only]
"The effect of a high bromide intake on the kinetics of iodide uptake and elimination in the thyroid and skin of adult male rats was studied. In rats fed a diet with sufficient iodine supply (> 25 microg I/d), the iodide accumulation in the skin predominated during the first hours after 131I iodide application. From this organ, radioiodide was gradually transferred into the thyroid. A high bromide intake (> 150 mg Br-/d) in these animals led to a marked decrease in iodide accumulation, especially by the thyroid, because of an increase in iodide elimination both from the thyroid and from the skin. In rats kept under the conditions of iodine deficiency (< 1 micro I/d), the iodide accumulation in the thyroid, but not in the skin, was markedly increased as a result of a thyrotropic stimulation. The effect of a high bromide intake (> 100 mg Br-/d) in these animals was particularly pronounced because the rates of iodide elimination were most accelerated both from their thyroid and from their skin."
Effect of high bromide levels in the organism on the biological half-life of iodine in the rat.Pavelka S, Babicky A, Vobecky M, Lener J. Biol Trace Elem Res. 2001 Summer;82(1-3):125-32. [abstract only]
"In experiments on rats, a significant influence of
an extraordinarily high bromide intake on the whole-body biological half-life of
iodine was established. Very high bromide intake (1) decreased the amount of
radioiodide accumulated in the thyroid, (2) changed the proportion between the
amount of iodine retained in the thyroid and the total amount of absorbed
iodine, (3) significantly shortened the biological half-life of iodine in the
thyroid from approximately 101 h to 33 h in animals maintained on an
iodine-sufficient diet and from 92 h to about 30 h in rats fed a low-iodine
diet, and (4) changed the time-course (added a further phase) of iodine
elimination from the body. These changes were caused, with high probability, by
an increase of iodine elimination by kidneys due to an excess of bromide. The
overall picture of iodine elimination in animals fed the low-iodine diet was
similar to that in animals maintained on iodine-sufficient diet."
Bromide kinetics and distribution in the rat. I. Biokinetics of 82Br-bromide.Pavelka S, Babicky A, Vobecky M, Lener J, Svandova E. Biol Trace Elem Res. 2000 Jul;76(1):57-66. [abstract only]
"Biological half-lives of bromine in 15 different organs and tissues of the rat, in addition to the whole-body half-life, were determined by measuring the radioactive concentration of 82Br-bromide in samples of tissues collected at the time intervals of 12-396 h from animals that continuously (up to 17 d) received 82Br-labeled bromide in their drinking water. The half-life values, calculated from the experimental data by the method of gradual estimates of the parameters in question with the SPSS statistical program, ranged from 94.3+/-14.6 h in the thyroid gland to 235.0+/-88.9 h in liver. In most of the studied tissues, the biological half-lives of bromine were shorter than in the whole body, in which it equaled 197.8+/-22.2 h. Significant correlation between the values of the steady-state concentration of bromide and of the biological half-life was found for most tissues (except for liver). The steady-state concentrations of 82Br in tissues are probably proportional to the magnitude of bromide space, and, consequently, of chloride space."
Bromide kinetics and distribution in the rat. II. Distribution of bromide in the body.Pavelka S, Babicky A, Vobecky M, Lener J. Biol Trace Elem Res. 2000 Jul;76(1):67-74. [abstract only]
"The distribution of 82Br-bromide in 15 different organs and tissues of rats has been determined by high-resolution gamma-ray spectrometry and by the scintillation counting technique at different times after the application of Na 82Br, either by subcutaneous injection or by continuous administration in the drinking water. The amount of 82Br-bromide in the various tissues reached its largest uptake within a few hours, and the concentration ratio of 82Br in the tissues to blood remained practically constant between 8 and 396 h after the application. The whole stomach of rats was the only organ of those investigated that had a larger uptake of 82Br than blood. Contrary to some previous findings, the concentration of radiobromide in the thyroid was found not to exceed that in the blood. A remarkably high concentration of 82Br was found in the skin, which represented, because of its large mass, the most abundant depot of bromide in the body of rats. The demonstrated excretion of bromide was mainly renal, at a rate of approximately 5% of the administered dose per 24 h."
Long-term action of potassium bromide on the rat thyroid gland.Velicky J, Titlbach M, Lojda Z, Duskova J, Vobecky M, Strbak V, Raska I. Acta Histochem. 1998 Feb;100(1):11-23. [abstract only]
"Male rats fed by a standard diet with determined of bromine and iodine content were exposed to a 133-day oral administration of KBr (100, 200, 400 mg Br-/l drinking water). Their thyroid glands showed increased growth of the epithelial cells reflected by a microfollicular rearrangement of the parenchyma due to proliferation of very small follicles with a low or zero content of colloid. Morphometric analysis of thyroids of Br(-)-exposed animals revealed a significant decrease in the volume of intrafollicular colloid and marked increase in the number of the smallest follicles (areas up to 100 and 100-300 micron 2). In addition, the nuclei of thyrocytes showed an increased number of mitoses. The vascularization was increased as well. In the blood plasma of the Br(-)-exposed animals the T4 concentration was significantly decreased in dependence on the bromine concentrations. Thyroglobulin immunoreactivity in the colloid of Br(-)-exposed animals decreased after administration of 400 mg Br-/l drinking water. Increasing concentrations of Br- in the drinking water caused an increased bromine concentration in the thyroid, a decreased iodine content and a decreased I/Br molar ratio. The changes in the rat thyroid caused by long-term administration of 100 mg Br-/l were similar to hyperplastic parenchymal goitre and were comparable to those induced in previous experiments by the same bromine concentration administered over a 16- and 66-day period respectively."
Biological half-life of bromine in the rat thyroid.Vobecky M, Babicky A, Lener J, Pavelka S. Physiol Res. 1997;46(5):385-9. [abstract only]
"The biological half-life of bromine in the rat thyroid was determined by measuring the radioactivity of thyroids of animals which continuously received 82Br labelled bromide in their food. The value of this half-life (110 h) is practically the same as the biological half-life of iodine. The rate of establishing the I/Br concentration ratio in the thyroid depends on the biological half-life of bromine. The mechanism of this process depends on the state of iodine supply. When the supply is sufficient, the iodine concentration in the thyroid remains constant, while during iodine deficiency the iodine atoms are replaced by atoms of bromine."
Expression of the proliferating cell nuclear antigen (PCNA) in the rat thyroid gland after exposure to bromide.Velicky J, Titlbach M, Lojda Z, Jelinek F, Vobecky M, Raska I. Acta Histochem. 1997 Nov;99(4):391-9. [abstract only]
"Analysis of expression of the proliferating cell nuclear antigen (PCNA) was used to determine the presumed hyperplastic character of morphological changes in the rat thyroid evoked by bromide administration. Male rats fed by a standard diet with determined iodine and bromine content were given potassium bromide. Control animals received no bromide. Experimental animals were given 10, 50 or 100 mg Br- per 11 drinking water for 16 and 66 days, or 100, 200, 400 mg Br-/l drinking water for 133 days. The thyroids of treated animals showed activation of growth of the epithelial follicular component as well as diffuse and focal microfollicular rearrangement of the parenchyma with higher follicular cells accompanied by a decrease of the amount of colloid even at low bromine concentrations (10-100 mg Br-/l drinking water). Using the PCNA-LI index (PCNA-positive nuclei.100/total number of follicular cell nuclei in the section), immunohistochemical analysis of PCNA in the nuclei of the follicular cells was carried out in parrafin sections. The index was significantly higher in bromide exposed animals (P < 0.01) and correlated well with the histological changes, with bromide concentration and with a increased mitotic activity of the follicular cells. PCNA analysis showed that morphological changes resembling a parenchymatic goitre reflect a microfollicular rearrangement of the thyroid of rats exposed to bromide and have the character of hyperplasia owing to the increased mitotic activity of the follicular epithelium."
Potassium bromide and the thyroid gland of the rat: morphology and immunohistochemistry, RIA and INAA analysis.Velicky J, Titlbach M, Duskova J, Vobecky M, Strbak V, Raska I. Ann Anat. 1997 Oct;179(5):421-31. [abstract only]
"The increasing environmental concentration of bromine has resulted in attempts to obtain information on its possibly deleterious effect on humans, particularly on a major target organ of this halogen i.e. the thyroid gland. In order to establish the morphological and functional effects of bromine on the thyroid, we have performed experiments on male rats which, in addition to a standard diet with an estimated iodine/bromine content, were fed for periods of 16 and 66 days with the small quantities of bromide expected to be encountered in the environment (10, 50 and 100 mg of Br-/l in drinking water). This treatment induced growth of the follicular epithelial component and microfollicular tissue rearrangement, a reduction of intrafollicular colloid, an increase in the height of the follicular cells and the number of mitoses, and it enhanced vascularization. Image analysis revealed a significant reduction in the volume of colloid, despite the accompanying rise in the number of minute follicles. The immunohistochemical positivity of the thyroglobulin fell in the microfollicular colloid of the exposed animals, although this was affected to a lesser extent in the larger follicles. The concentration of bromine in the thyroid increased with the amount of bromine intake, while at the same time the molar ratio of iodine/bromine decreased. The plasma level of T4 was lowered after both 16 and 66 days of treatment, but the T3 level only after 66 days treatment. The level of TSH did not exhibit any significant change. The observed changes, which have a parenchymatous goitre-like character, may have a direct relevance for human medicine, since the concentrations of bromide chosen in these experiments are readily encountered in the environment."
Effect of increased bromide intake on iodine excretion in rats.Vobecky M, Babicky A, Lener J. Biol Trace Elem Res. 1996 Dec;55(3):215-9. [abstract only]
"The time course of iodine excretion in adult male rats substantially differs from bromine excretion. Bromine is excreted at a single rate, whereas iodine evinces two excretion rates. Even a strong increase in bromide intake in experimental animals failed to affect the rate of iodine excretion but it lowered the fraction of iodine accumulated in the thyroid gland by 20% probably by affecting the transport of iodide into the thyroid gland."
Interaction of bromine with iodine in the rat thyroid gland at enhanced bromide intake.Vobecky M, Babicky A, Lener J, Svandova E. Biol Trace Elem Res. 1996 Sep;54(3):207-12. [abstract only]
"In experiments with rats, we have found that at enhanced intake of bromide, bromine does not replace chlorine in the thyroid; it replaces iodine. Under our experimental conditions, more than one-third of the iodine content in the thyroid was replaced by bromine. In the thyroid, bromine probably remained in the form of bromide and, in proportional to its increased concentration, the production of iodinated thyronines decreased, with the sum of the iodine and bromine concentrations being constant at the value of 20.51 +/- 1.16 mumol/g dry wt of the thyroid. In contrast to other organs, the biological behavior of bromine in the thyroid is not similar to the biological behavior of chlorine but resembles more that of iodine."
Effect of enhanced bromide intake on the concentration ratio I/Br in the rat thyroid gland.Vobecky M, Babicky A. Biol Trace Elem Res. 1994 Fall;43-45:509-16. [abstract only]
"Interaction of bromine with iodine was studied in the rat thyroid gland under the conditions of different bromide intake. Bromine and iodine in the thyroid dry weight were determined by instrumental neutron activation analysis (INAA). It was found that with increased bromide intake the bromine concentration in the thyroid gland increased with simultaneous decrease in the iodine concentration. The change in the I/Br concentration ratio depends on a number of halogen binding positions and on the bromide supply. The I/Br parameter reacts sensitively to the changes of bromide intake already in the region of low bromine concentration levels."
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