Impact of high bromide intake in the rat dam on iodine transfer to the sucklings.

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.

Effect of high bromide levels in the organism on the biological half-life of iodine in the rat.

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.

High bromide intake affects the accumulation of iodide in the rat thyroid and skin.

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.

Bromide kinetics and distribution in the rat. I. Biokinetics of 82Br-bromide.

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.

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.

Biological half-life of bromine in the rat thyroid.

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.

Effect of increased bromide intake on iodine excretion in rats.

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.

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.

Study of distribution and interaction of arsenic and selenium in rat thyroid.

Seventy-eight Wistar weanling rats were pretreated with arsenate (100 mg/L As), selenite (1 mg/L Se), and arsenate (100 mg/L As) plus selenite (1 mg/L Se) added to the drinking water. After 4 w, all the animals were sacrificed and serum T3 and T4 were determined by double-antibody radioimmunoassay. Thyroid tissue concentrations of As and Se were determined in female rats by neutron activation analysis, and tissue specimens were examined histopathologically. For both sexes, the measurements indicated that T4/T3 was lowest in the Se group, intermediate in the As group, and highest in the controls. Corrected for the mean value of the controls, mean As concentration of thyroid tissue was of the same magnitude in the group pretreated with As + Se as the sum of the mean As concentration in the groups pretreated with As or Se alone. The outcome was symmetric with regard to the Se concentration: In the As + Se pretreated group, the mean Se concentration was of the same magnitude as the sum of the mean Se concentration in the groups pretreated with As or Se alone. Thus, As and Se tended to accumulate in the thyroid tissue. Postmortem examination showed that the thyroid tissue of rats pretreated with As alone exhibited obvious, toxic changes, whereas only minor or no changes were found in the tissues of the groups pretreated with Se or As + Se, and in the tissues of the controls. Multivariate analyses demonstrated that s-T4 and s-T3 were significantly correlated with sex, that s-T3 was positively correlated (p < or = 0.001) with Se pretreatment, and that the T4/T3 ratio was negatively correlated with both As (p < or = 0.012) and Se pretreatment (p < or = 0.001). The results were discussed in relation to the cancer preventive effect of Se.

Vanadium levels in urine and cystine levels in fingernails and hair of exposed and normal persons.

Vanadium was determined by radiochemical neutron activation analysis (RNAA) with proven accuracy in urine of workers occupationally exposed to vanadium-rich dust in a vanadium pentoxide production plant, and values in the range of 3.02-762 ng/mL (median 33.0 ng/mL) were found. In a control group consisting of administrative workers of the plant, urinary vanadium levels were found in the range of 1.05-53.4 ng/mL (median 2.53 ng/mL), whereas in an another control group of occupationally nonexposed persons, these values amounted to 0.066-0.489 ng/mL (median 0.212 ng/mL). Accuracy of the results was tested by analysis of reference material IAEA A-13 Animal Blood and NIST SRM-1515 Apple Leaves, and very good agreement was found with literature and the NIST certified values, respectively. Unlike urine, no significant differences were found for cystine levels in fingernails and hair of exposed and control persons.

Effects of orally administered vanadium on the immune system and bone metabolism in experimental animals.

Experiments were carried out to gain more information on the effects of long term exposure to low doses of vanadium administered to mice and rats in drinking water. The selective immunotoxic effects of vanadium were depression of phagocytosis, splenotoxicity, enlargement of spleen, elevation of peripheral blood leucocytes and T and B cell activation. Vanadium accumulates in hard tissues and influences the mineralisation of epiphyseal cartilage. This effect is obviously evident in young animals. Significant differences in vanadium concentration were found between young and adult animals.

Vanadium levels in hair and blood of normal and exposed persons.

Vanadium was determined by both instrumental neutron activation analysis (INAA) and NAA with radiochemical separation (RNAA) in hair of normal children and of children potentially exposed by accidental drinking of vanadium contaminated water (long-term, low-dose exposure). Vanadium hair levels in the two groups did not differ significantly and were in the range 46-313 micrograms/kg (median 98 micrograms/kg) and 24-235 micrograms/kg (median 88 micrograms/kg for the normal and exposed groups, respectively. Using RNAA with proven reliability at the ultratrace level, vanadium was determined in whole blood of the exposed and normal children, normal adults and workers professionally exposed to vanadium in a factory producing vanadium pentoxide. Significantly increased vanadium concentrations were found in blood of exposed children (range 0.018-0.239 micrograms/l, median 0.078 micrograms/l) compared to normal children (range 0.024-0.226 micrograms/l, median 0.042 micrograms/l), while no differences could be detected between blood vanadium levels of normal children and normal adults (range 0.032-0.095 micrograms/l, median 0.056 micrograms/l). Preliminary results for vanadium in blood of occupationally highly exposed persons showed values 2-4 orders of magnitude higher than in normal adults.

Reticulocyte-dependent labeling alterations of red cell membrane in pyruvate kinase deficiency anemia.

The radioactive labeling of spectrin using the pentavalent complex of molybdenum-99 was applied to the study of membrane protein in pyruvate kinase deficient red cells. Compared to the control, the labeling profile of the enzymopathic red cell membrane proteins remained generally unchanged but the molybdenum uptake was found to depend largely on the reticulocyte count. This finding may reflect changes during the cell maturation.

Structural analogy among mammalian spectrins and spectrin-like proteins revealed by molybdenum labeling.

Pentavalent complex of 99Mo with ascorbic acid binds in vitro to the plasma membranes of human, rabbit, rat and mouse red cell membranes and to bovine synaptic and rat intestinal brush border membranes. Red cell spectrins and spectrin-like proteins from non-erythroid cells were determined as the molybdenum-binding proteins in the membranes. Specificity of this binding among all membrane proteins suggests structural analogy in this group of proteins.

The mechanism of action of molybdenum and tungsten upon collagen structures in vivo.

The effect of in vivo administration of molybdenum (as sodium molybdate) and tungsten (as sodium tungstate) was investigated in the skin of laboratory rats. It was proved that the amount of both bound molybdenum and tungsten in collagen is relatively small being 0.05 and 0.06 moles per mole respectively. Besides the fraction of firmly bound molybdenum and tungsten a much higher extractable pool of both these metals was found. It was also demonstrated that in vivo shadowing of collagen is caused by the fraction of loosely bound metals. On the other hand pronounced changes were shown in the mechanical properties of connective tissue after molybdate and tungstate administration. Surprisingly, the change in mechanical properties indicated a lower level of cross-linking after the administration of the investigated metals. It is therefore concluded that bitopical binding of molybdenum and tungsten in the collagen structure is unlikely. It also appears that the biological effect of these metals is due to the competition with copper and the interference with the physiological cross-linking reactions based on the partial blockade of lysyloxidase.

Effects of molybdenum on the organism (a review).

Molybdenum belongs to a group of essential microelements and occurs in all components of the environment. Major Mo sources for man are foods, especially vegetable, to a lesser extent drinking water. Its metabolism is primarily influenced by interaction with other metals, specifically copper and iron. In the organism it is primarily accumulated in the liver, kidneys, skin and hard tissues. In the blood it binds specifically with alpha-2-macroglobulin, in the erythrocytic membrane with spectrin; it enhances the osmotic resistance of red blood cells. From the organism it is eliminated in the urine, bile and feces. The biochemical importance of molybdenum lies in that it catalyzes the oxidation of xanthine and purine bases and the reduction of nitrates and molecular nitrogen; it is also present in the prosthetic group of flavoprotein enzymes. As shown in both epidemiological and animal studies, molybdenum ions may prevent dental caries. Long-term overexposure to Mo may produce molybdenosis (teart) in cattle. Increased exposures of humans may be primarily encountered in the foundry industry, but the toxic manifestations are invariably nonspecific, similarly as in the case of other heavy metals. Molybdenum-exposed workers may also show elevated uric acid concentrations in their blood, simultaneously with clinical symptoms resembling gout (gout-like syndrome). A similar finding may also occur among individuals living in areas characterized by elevated molybdenum and decreased copper contents in soil. The maximum allowable concentration limits established for soluble and insoluble molybdenum compounds in the workplace air have been accepted in many countries, but their values vary in a wide range. No specific exposure test for molybdenum has been developed as yet.

Specific molybdenum binding to spectrin subunits.

Molybdenum in the form of its pentavalent complex binds primarily to spectrin when incubated with erythrocytes. Only the band 1 subunit is involved in this interaction thus indicating some structural differences between spectrin subunits.