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The effects of fluoride on thyroid hormones in rabbits
Abstract
In this study, our objective was to determine blood T3, T 4 and TSH levels in rabbits, which were administered fluoride chronically. Twenty one male rabbits were divided into three groups. The rabbits in group I (control), group II and III were administered, respectively, normal drinking water (containing 0.07 ppm fluoride), drinking water containing 10 ppm fluoride and water containing 40 ppm fluoride for 70 days. On the days 21 and 70 blood was taken and plasma T3, T4, TSH and fluoride levels were studied. According to the results obtained a statistically significant increase was observed in the T3 level of the rabbits receiving fluoride at 40 ppm level for 70 days compared with controls, and a statistically significant decrease was detected in T4 level. Plasma fluoride level increased in proportion to the amount and duration of the fluoride administered.
... The most likely hypothesis is that fluoride may compete with iodide when thyroxin is synthesized, but this effect may be dependent upon the level of both iodide and fluoride intake ( Wheeler and Fell 1983). Bilgili et al. (2004) reported a statistically significant increase in T 3 level of the rabbits receiving fluoride at 40 ppm level for 70 days as compared to control, and a significant decrease in T 4 level as compared to control animals. It was postulated that fluoride administered has no direct effect on pituitary, hypothalamus and thyroid glands, but is considered to precipitate the conversion of T 4 into T 3 in peripheral tissues. ...
Twelve male buffalo calves of 10 to 12 months of age were divided into 3 groups of four each. They were fed wheat straw+concentrate mixture +3 Kg greens. The chemical composition of the diet was same in all the three groups except fluoride which was added (as NaF) in concentrate mixture of group B and C to make the final fluoride concentration 30 ppm and 60 ppm respectively. The animals were kept on scheduled diet for a period of 90 days. Body weights were recorded at the start of the experiment and at fortnightly interval thereafter. Analysis of data revealed that the dry matter intake decreased non significantly in group B and C as compared to control group. A significant decrease in serum calcium and a significant increase in phosphorus concentration were observed in group C animals. A significant increase was observed in alkaline phosphatase activity in group C animals. A non significant decrease was observed in T4 values in group C animals. On the basis of these results it could be concluded that fluoride in the diet of buffalo calves @ 30 ppm is a safe level whereas 60 ppm has affected the blood metabolites.
Iodine is a raw material for the thyroid production of hormone which is on the major external control of TSH. The thyroid adaptation to iodine deficiency consists in an increasing iodine concentration from the circulation, an enhancing iodination of the tyrosyl residues in thyrogtobulin, a decreasing iodine storage associated to a better recycling of non hormonal iodine and thyroid hyperplasia to provide more synthetic possibilities. Genetic variation and environmental factors explain the wide variation of individuals response to iodine deficiency resulting in a high prevalence of goiter, a mild TSH level increase or overt hypothyroidism. At long term iodine deficiency may have severe pathological consequences and induce neuropsychological deficits in school-children. A policy of iodine supplementation mainly by iodized salt must be undertaken in many areas in the world. Effects of an iodine excess on thyroid function are variable depending upon the underlying thyroid disorder and ambient iodine intake. The most subjects remain euthyroid by mechanisms of autoregulation based on an inhibition of thyroid hormone synthesis and a decrease in the thyroide iodide trap. Euthyroid individuals from high iodine intake areas or those with a history of lymphocytic thyroiditis, treated Graves'disease or subtotal thyroidectomy develop hypothyroidism. On the other hand iodine induced hyperthyroidism is more common in areas of iodine deficiency and in older patients with nodular goiter.
IN drinking-water, concentrations of fluoride in excess of 100 p.p.m. inhibit bone growth in experimental animals, and this effect has usually been explained as a local action of fluoride on bone1. That fluoride acts in this way is certainly true in tissue culture2. In the intact animal, however, large resorption cavities containing fibrous tissue and many osteoclasts are often seen in the long bones and vertebrae. These resorption cavities, which have received scant attention since their original observation by Roholm3, are difficult to explain as a purely local effect of fluoride: it is not easy to reconcile the fact that fluoride appears selectively to depress osteoblasts on one hand, yet concomitantly to stimulate osteoclasts on the other, despite the fact that these latter cells contain at least one enzyme—acid phosphatase—that is known to be inhibited by fluoride in vitro
4. Furthermore, smaller concentrations of fluoride, given to rabbits, appeared to exert their effect on bone principally by reducing resorption5.
Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases, which convert thyroxine (T4) to the more metabolically active 3,3'-5 triiodothyronine (T3). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also labeled with 75Se by in vivo treatment of rats with 75Se-Na2SeO3. Thus, the type I iodothyronine 5'-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent selenium deficiency could be a major determinant of the severity of iodine deficiency.
The contribution of the stomach and the small intestine to absorption of fluoride from the gastrointestinal tract was examined in rats. Fasted adult male rats weighing approximately 350 g were given 50 micrograms of fluoride in 1 ml of water by stomach intubation, with 14C-labeled polyethylene glycol as a marker of water movement through the gastrointestinal tract. Rats were killed at intervals up to 120 min, and the stomach, duodenum, jejunum, ileum, distal ileum and cecum were rapidly clamped and removed for fluoride analysis and 14C counting. Approximately 90% of the fluoride dose was absorbed in 120 min. Peak plasma fluoride concentration occurred 10 min after intubation and began to decline after 40 min as the rate of fluoride absorption slowed. Absorption from the stomach was derived from rates of gastric emptying and remaining fluoride. Even at 10 min after intubation, when the bulk of the fluoride remained in the stomach, only approximately 25% of fluoride absorption had occurred from the stomach and 75% from the small intestine. After 120 min, 19.8% of total fluoride absorption had occurred from the stomach. Although the stomach is unquestionably a significant site for fluoride absorption, its contribution is much smaller than that of the small intestine.
The purpose of this study was to determine whether total serum calcium, parathyroid gland structure, and/or levels of parathyroid hormone, 1,25 and 24,25 DHCC, are altered in pigs with dental and skeletal fluorosis. Eight experimental animals receiving 2 mg F-/kg b.w. per day from age 8-14 months were compared with eight controls. Concentrations of plasma fluoride and total plasma calcium were assessed at intervals throughout the experiment and during a 48 hour period at day 110-111 of the experiment. At the same time, concentrations of immunoreactive parathyroid hormone were measured using a homologous labeled antibody for porcine hormone, and a radioimmunoassay was used to assess concentrations of 1,25 DHCC and 24,25 DHCC. Parathyroid tissue volumes were assessed at the end of the experiment by quantitative histology using volumetry and point counting. Plasma fluoride increased from 0.0007 +/- 0.0001 mmol/liter to 0.0127 +/- 0.002 mmol/liter in pigs receiving fluoride. In spite of this increase, total plasma calcium remained the same throughout the experiment. Volumes of parathyroid tissue, and levels of circulating parathyroid hormone 1,25 DHCC and 24,25 DHCC, were not significantly changed. It was therefore concluded that disturbance of calcium homeostasis is not an obligatory finding in dental and skeletal fluorosis and consequently does not play an essential role in the pathogenesis of these hard tissue lesions.
Adenyl cyclase activity of sheep thyroid mitochondrial (9000 ×g) fractions was determined by measuring the rate of formation of radioactive 3′,5′-adenosine monophosphate from 32P-labeled adenosine triphosphate. Thyrotropin (TSH) and sodium fluoride added in vitro markedly increased thyroid adenyl cyclase activity by a mechanism unrelated to inhibition of phosphodiesterase or adenosine triphosphatase. Several similarities in the TSH- and sodium fluoride-activated adenyl cyclase system were found. Thus, proportionality to thyroid protein concentration and pH and ATP concentration optima were the same for both TSH and NaF. Repeated freezing and thawing of thyroid homogenates or mitochondria reduced the adenyl cyclase response to TSH and NaF to about the same decree. However, activation of adenyl cyclase by maximally effective concentrations of sodium fluoride was increased by the addition of maximal doses of TSH, indicating differences in the sites of action of these compounds. In addition, the α- and β-adrenergic blocking drugs, phentol,amine and propranolol, greatly inhibited TSH effects on adenyl cyclase, while sodium fluoride-induced enzyme activation was unaffected. These data suggest that, although the adenyl cyclase systems in thyroid that respond to TSH and sodium fluoride have many characteristics in common, these compounds interact at different sites on the enzyme system to elicit their effects. (Endocrinology 86: 346, 1970)
Adenyl cyclase activity of sheep thyroid mitochondrial (9000 ×g) fractions was determined by measuring the rate of formation of radioactive 3′,5′-adenosine monophosphate from 32P-labeled adenosine triphosphate. Thyrotropin (TSH) and sodium fluoride added in vitro markedly increased thyroid adenyl cyclase activity by a mechanism unrelated to inhibition of phosphodiesterase or adenosine triphosphatase. Several similarities in the TSH- and sodium fluoride-activated adenyl cyclase system were found. Thus, proportionality to thyroid protein concentration and pH and ATP concentration optima were the same for both TSH and NaF. Repeated freezing and thawing of thyroid homogenates or mitochondria reduced the adenyl cyclase response to TSH and NaF to about the same decree. However, activation of adenyl cyclase by maximally effective concentrations of sodium fluoride was increased by the addition of maximal doses of TSH, indicating differences in the sites of action of these compounds. In addition, the α- and β-adrenergic blocking drugs, phentol,amine and propranolol, greatly inhibited TSH effects on adenyl cyclase, while sodium fluoride-induced enzyme activation was unaffected. These data suggest that, although the adenyl cyclase systems in thyroid that respond to TSH and sodium fluoride have many characteristics in common, these compounds interact at different sites on the enzyme system to elicit their effects. (Endocrinology 86: 346, 1970)
The increasing use of fluoride for prevention of dental caries poses the problem as to whether this halogen has antagonistic properties towards iodine, whereby it could hamper the success of iodine prophylaxis of endemic goitre. Review of the literature shows that some authors have found an inhibition by fluoride of various steps of thyroid hormone biosynthesis in animal experiments. By and large, the inhibition was only slight and it was elicited only with fluoride doses greatly in excess of those recommended for caries prevention. The inhibition was not consistently present and other authors could not confirm it in comparable experiments. There is no convincing evidence that fluoride produces true goitres with epithelial hyperplasia in experimental animals. There are some reports based on casual observations that fluoride is goitrogenic in man. On the other hand, several good studies with adequate exposed and control populations failed to detect any goitrogenic effect of fluoride in man. It is noteworthy in particular that fluoride does not potentiate the consequences of iodine deficiency in populations with a borderline or low iodine intake. Published data failed to support the view that fluoride, in doses recommended for caries prevention, adversely affects the thyroid.
The existence of G protein-dependent and -independent mechanisms activated by sodium fluoride was examined in muscle cells isolated separately from the circular and longitudinal layers of guinea pig intestine. The cells were transiently permeabilized by incubation with Trans. Port Reagent in the presence or absence of GDP beta S (100 microM) and then re-sealed. In the absence of GDP beta S, NaF (1 mM) induced contraction and caused an increase in [Ca2+]i, IP3 and diacylglycerol levels and in protein kinase C (PKC) activity in both cell types. In the presence of GDP beta S, the increases in IP3, DAG and PKC were abolished whereas contraction and the increase in [Ca2+]i were partly inhibited. Residual contraction and [Ca2+]i were abolished by the Ca2+ channel blocker, methoxyverapamil. We conclude that contraction and Ca2+ mobilization induced by NaF is mediated by G protein activation as well as by a G protein-independent mechanism involving activation of plasmalemmal Ca2+ channels.
This study describes alterations in the nervous system resulting from chronic administration of the fluoroaluminum complex (AlF3) or equivalent levels of fluoride (F) in the form of sodium-fluoride (NaF). Twenty seven adult male Long-Evans rats were administered one of three treatments for 52 weeks: the control group was administered double distilled deionized drinking water (ddw). The aluminum-treated group received ddw with 0.5 ppm AlF3 and the NaF group received ddw with 2.1 ppm NaF containing the equivalent amount of F as in the AlF3 ddw. Tissue aluminum (Al) levels of brain, liver and kidney were assessed with the Direct Current Plasma (DCP) technique and its distribution assessed with Morin histochemistry. Histological sections of brain were stained with hematoxylin & eosin (H&E), Cresyl violet, Bielschowsky silver stain, or immunohistochemically for beta-amyloid, amyloid A, and IgM. No differences were found between the body weights of rats in the different treatment groups although more rats died in the AlF3 group than in the control group. The Al levels in samples of brain and kidney were higher in both the AlF3 and NaF groups relative to controls. The effects of the two treatments on cerebrovascular and neuronal integrity were qualitatively and quantitatively different. These alterations were greater in animals in the AlF3 group than in the NaF group and greater in the NaF group than in controls.
Iodine is an scarce metalloid, essential for life, more abundant in the aquatic ecosystem than in land. Marine species do not need to store and transform the inorganic iodine into organic iodine through the thyroid gland. Adaptation to terrestrial ecosystem has required phylogenetic processes, and animal species have used different strategies to solve the iodine captation problem according to their needs. Jellyfish lack of thyroid gland while lampery developed the thyroid gland during evolution in order to adapt to the terrestrial ecosystem. This review is a comparative phylogenetic study of thyroid gland development and iodine physiology, includes functional disorders, as well as iodine captation ability and requirements during growth and reproduction in different species.