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Iodine Research
Resource Network of The Iodine Movement
IODINE AND OTHER HALOGENS
BROMIDE
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.
BROMIDE
- Pavelka, et al, have studied the metabolism of bromide and its interference with the
metabolism of iodine, 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. They
have also established the biological half-life of bromide in rats. - Van Leeuwen, et al, have focused on the toxicology of the bromide ion and its effects on
the thyroid, skin, endocrine system, reproduction, and central nervous system. - Rauws has studied the pharmacokinetics of the bromide ion.
- Simchowitz has studied the interactions of bromide, iodide, fluoride, and chloride in human
neutrophils. - Zhang looks at the effects of dietary intake of cereals and marine products on urinary
bromide levels. - Buchberger focuses on the effects of bromide on thyroid hormones.
- INCHEM discusses the toxicology of the bromide ion.
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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