Fluoride Abstracts 2

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Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.
            (Adedara et al., 2016) Download
Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

[Action of the body fluorine of healthy persons and thyroidopathy patients on the function of hypophyseal-thyroid the system].
            (Bachinskiĭ et al., 1985) Download
Altogether 123 persons were examined: 47 healthy persons, 43 patients with thyroid hyperfunction and 33 with thyroid hypofunction. It was established that prolonged consumption of drinking water with a raised fluorine content (122 +/- 5 mumol/l with the normal value of 52 +/- 5 mumol/l) by healthy persons caused tension of function of the pituitary-thyroid system that was expressed in TSH elevated production, a decrease in the T3 concentration and more intense absorption of radioactive iodine by the thyroid as compared to healthy persons who consumed drinking water with the normal fluorine concentration. The results led to a conclusion that excess of fluorine in drinking water was a risk factor of more rapid development of thyroid pathology. Indicators of the fluorine content in daily urine provide most of the information on changes of the fluorine amount in the body.

Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride.
            (Banji et al., 2013) Download
The study investigated the role of Spirulina platensis in reversing sodium fluoride-induced thyroid, neurodevelopment and oxidative alterations in offspring of pregnant rats. The total antioxidant activity, phycocyanins, and β carotene content were quantified in Spirulina. Thirty female pregnant rats were allocated to six groups and treatment initiated orally from embryonic day (ED) 6 to postnatal day (PND) 15. Treatment groups included control, Spirulina alone, sodium fluoride (20 mg/kg) alone, and sodium fluoride along with Spirulina (250 and 500 mg/kg). Serum fluoride levels were determined on ED 20 and PND 11. Offspring were subjected to behavioural testing, estimation of thyroid levels, oxidative measurements in brain mitochondrial fraction and histological evaluation of the cerebellum. Fluoride-induced alterations in thyroid hormones, behaviour and increased oxidative stress. Spirulina augmented the displacement of fluoride, facilitated antioxidant formation, improved behaviour and protected Purkinje cells. Supplementing Spirulina during pregnancy could reduce the risk of fluoride toxicity in offspring.

Fluoride toxicity and status of serum thyroid hormones, brain histopathology, and learning memory in rats: a multigenerational assessment.
            (Basha et al., 2011) Download
High-fluoride (100 and 200 ppm) water was administered to rats orally to study the fluoride-induced changes on the thyroid hormone status, the histopathology of discrete brain regions, the acetylcholine esterase activity, and the learning and memory abilities in multigeneration rats. Significant decrease in the serum-free thyroxine (FT4) and free triiodothyronine (FT3) levels and decrease in acetylcholine esterase activity in fluoride-treated group were observed. Presence of eosinophilic Purkinje cells, degenerating neurons, decreased granular cells, and vacuolations were noted in discrete brain regions of the fluoride-treated group. In the T-maze experiments, the fluoride-treated group showed poor acquisition and retention and higher latency when compared with the control. The alterations were more profound in the third generation when compared with the first- and second-generation fluoride-treated group. Changes in the thyroid hormone levels in the present study might have imbalanced the oxidant/antioxidant system, which further led to a reduction in learning memory ability. Hence, presence of generational or cumulative effects of fluoride on the development of the offspring when it is ingested continuously through multiple generations is evident from the present study.

Oestradiol protects against the harmful effects of fluoride more by increasing thiol group levels than scavenging hydroxyl radicals.
            (Dlugosz et al., 2009) Download
The aim of the study was to investigate the role of oestrogens in free radical detoxication upon exposure to fluoride. Interactions between xenobiotics and oestrogens need to be investigated, especially as many chemicals interact with the oestrogen receptor. It is still unknown whether free radical-generating xenobiotics can influence the antioxidative ability of oestradiol (E(2)). In an in vitro examination of human placental mitochondria, thiobarbituric active reagent species (TBARS), hydroxyl radical ((*)OH) generation and protein thiol (-SH) groups were detected. 17beta-E(2) was examined in physiological (0.15-0.73 nM) and experimental (1-10 microM) concentrations and sodium fluoride (NaF) in concentrations of 6-24 microM. E(2) in all the concentrations significantly decreased lipid peroxidation measured as the TBARS level, in contrast to NaF, which increased lipid peroxidation. Lipid peroxidation induced by NaF was decreased by E(2). The influence of E(2) on (*)OH generation was not very significant and depended on the E(2 )concentration. The main mechanism of E(2) protection in NaF exposure appeared to be connected with the influence of E(2 )on thiol group levels, not (*)OH scavenging ability. The E(2) in concentrations 0.44-0.73 nM and 1-10 microM significantly increased the levels of -SH groups, in contrast to NaF, which significantly decreased them. E(2) at every concentration reversed the harmful effects of NaF on -SH group levels. No unfavourable interactions in the influence of E(2) and NaF on TBARS production, (*)OH generation, or -SH group levels were observed. The results suggest that postmenopausal women could be more sensitive to NaF-initiated oxidative stress.

Study of thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in subjects with dental fluorosis.
            (Hosur et al., 2012) Download
OBJECTIVE:  Apart from its well-known deleterious dental and skeletal effects, fluoride excess can have toxic effects on many other tissues. Fluoride, when in excess, is known to interfere with thyroid gland function. Fluoride-induced thyroid disturbances similar to those observed in iodine deficiency state in spite of adequate iodine intake have been documented. Similar thyroid disturbances in individuals with dental fluorosis have not been well studied in populations with endemic fluorosis. This work was undertaken to study the effects of fluoride-induced thyroid disturbances in individuals with dental fluorosis. METHODS:  The study group included 65 subjects with dental fluorosis from endemic fluorosis populations. An additional control group was comprised of 10 subjects without dental fluorosis. The drinking water fluoride levels of the study populations were analyzed. Serum free FT3, FT4, and TSH levels of both groups were assessed. RESULTS:  All subjects with dental fluorosis had serum levels of thyroid hormones (FT3, FT4, and TSH) within the normal range, with the exception of 1 individual, who had elevated levels of TSH. Statistical significance was found when FT3 and TSH values were compared with different Dean's index groups by a 1-way ANOVA test: FT3 (F = 3.4572; P=.0377) and TSH (F = 3.2649 and P=.0449). CONCLUSIONS:  Findings of this study did not show any significant alterations in the levels of the thyroid hormones FT3, FT4, and TSH in subjects with dental fluorosis. Our observations suggest that thyroid hormone levels were not altered in subjects with dental fluorosis. Hence, future studies of this kind, along with more detailed investigations are needed.

Fluoride-induced disruption of reproductive hormones in men.
            (Ortiz-Pérez et al., 2003) Download
Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27 mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13 mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27 mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.

Management of fluoride induced testicular disorders by calcium and vitamin-E co-administration in the albino rat.
            (Sarkar et al., 2006) Download
Fluoride contamination of drinking water can disrupt male gametogenesis and steroidogenesis and induce testicular oxidative stress. Treatment of rats with sodium fluoride at the dose of 20 mg/kg/day for 28 days resulted in significant diminution of testicular Delta5,3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-hydroxysteroid dehydrogenase (HSD) activities and low plasma levels of testosterone, follicular stimulating hormone (FSH) and leutinizing hormone (LH). Spermatogenesis inhibited after sodium fluoride treatment has been assessed here by the quantification of different generation of germ cells like spermatogonia A (ASg), preleptotene spermatocyte (PLSc), midpachytene spermatocyte (MPSc) and step 7 spermatid (7Sd) at stage VII of seminiferous epithelial cycle. Furthermore, fluoride treatment was associated with low activities of testicular, prostatic and epididymal catalase (CAT), superoxide dismutase (SOD) and peroxidase along with elevation of malondialdehyde (MDA) and conjugated dienes (CD) in those tissues. Co-administration of calcium and Vitamin-E with fluoride resulted in a significant recovery from testicular disorders and oxidative stress in the testis and male accessory sex organs. The results of this study demonstrate that fluoride exposure, at the dose available in drinking water in contaminated areas, led to inhibition of testicular gametogenesis and steroidogenesis in association with oxidative stress in the testis and male accessory sex organs, which are protected significantly by dietary agents like Vitamin-E and calcium.

γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice.
            (Yang et al., 2016) Download
AIM:  This study evaluated the protective effects of γ-aminobutyric acid (GABA), a non-protein amino acid and anti-oxidant, against fluoride-induced hypothyroidism in mice. MAIN METHODS:  Light microscope sample preparation technique and TEM sample preparation technique were used to assay thyroid microstructure and ultrastructure; enzyme immunoassay method was used to assay hormone and protein levels; immunohistochemical staining method was used to assay apoptosis of thyroid follicular epithelium cells. KEY FINDINGS:  Subacute injection of sodium fluoride (NaF) decreased blood T4, T3 and thyroid hormone-binding globulin (TBG) levels to 33.98 μg/l, 3 2.8 ng/ml and 11.67 ng/ml, respectively. In addition, fluoride intoxication induced structural abnormalities in thyroid follicles. Our results showed that treatment of fluoride-exposed mice with GABA appreciably decreased metabolic toxicity induced by fluoride and restored the microstructural and ultrastructural organisation of the thyroid gland towards normalcy. Compared with the negative control group, GABA treatment groups showed significantly upregulated T4, T3 and TBG levels (42.34 μg/l, 6.54 ng/ml and 18.78 ng/ml, respectively; P<0.05), properly increased TSH level and apoptosis inhibition in thyroid follicular epithelial cells. SIGNIFICANCE:  To the best of our knowledge, this is the first study to establish the therapeutic efficacy of GABA as a natural antioxidant in inducing thyroprotection against fluoride-induced toxicity.

Effects of sodium fluoride on reproductive function in female rats.
            (Zhou et al., 2013b) Download
The aim of this study was to investigate the effects of sodium fluoride (NaF) on female reproductive function and examine the morphology of the ovaries and uteri of rats exposed to NaF. Eighty female Sprague-Dawley (SD) rats were divided randomly into four groups of 20: one control group and three NaF treated groups. The three NaF treated groups received 100, 150, and 200 ppm, respectively, of NaF for 6 months via their drinking water, while the control group (GC) received distilled water. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), progesterone (P) and estradiol (E2) were measured using an enzyme-linked immunosorbent assay. Pathomorphological evaluation of the uteri and ovaries was conducted after staining with hematoxylin-eosin and immunohistochemistry. The rate of successful pregnancy in the NaF-treated groups declined in a dose-dependent manner. The concentration of reproductive hormones was significantly lower in the three NaF-treated groups, and the endometrium was damaged. The maturation of follicles was inhibited. In addition, the total number of follicles of all types was significantly lower in the NaF-treated groups. These results suggest that female reproductive function is inhibited by NaF and that exposure to NaF causes ovarian and uterine structural damage. NaF may thus significantly reduce the fertility of female rats.

The toxicity mechanism of sodium fluoride on fertility in female rats.
            (Zhou et al., 2013a) Download
Recognition of the harmful effects of sodium fluoride (NaF) on human reproduction is increasing, especially as it relates to female reproduction. However, the mechanism by which NaF interferes with female reproduction is unclear. The aims of the present study were to investigate the effects of fluoride exposure on female fertility and to elucidate the mechanisms underlying these effects. Female Sprague-Dawley rats were divided into three groups: one control group and two NaF-treated groups (100 and 200 mg/L in the drinking water for 12 weeks). Several parameters were evaluated, including: (i) fluoride concentrations; (ii) estrogen (E2) and progesterone (P) concentrations; (iii) estrogen receptor alpha protein (ERα); (iv) progesterone receptor (PgR) protein; (v) follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) protein. The results indicated that administration of NaF lead to significant decreases in E2 and P levels in the serum and in the expression of FSHR protein. In addition, fluoride exposure significantly increased Erα and PgR protein expression levels and LHR protein expression. These results suggest that the reproductive hormone reduction and the abnormalities of related receptor proteins expression are important factors underlying the decreased fertility observed in female rats that have been exposed to NaF.

 


References

Adedara, IA, et al. (2016), ‘Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.’, Biol Trace Elem Res, PubMed: 27334436
Bachinskiĭ, PP, et al. (1985), ‘[Action of the body fluorine of healthy persons and thyroidopathy patients on the function of hypophyseal-thyroid the system].’, Probl Endokrinol (Mosk), 31 (6), 25-29. PubMed: 4088985
Banji, D, et al. (2013), ‘Investigation on the role of Spirulina platensis in ameliorating behavioural changes, thyroid dysfunction and oxidative stress in offspring of pregnant rats exposed to fluoride.’, Food Chem, 140 (1-2), 321-31. PubMed: 23578649
Basha, PM, P Rai, and S Begum (2011), ‘Fluoride toxicity and status of serum thyroid hormones, brain histopathology, and learning memory in rats: a multigenerational assessment.’, Biol Trace Elem Res, 144 (1-3), 1083-94. PubMed: 21755305
Dlugosz, A, A Roszkowska, and M Zimmer (2009), ‘Oestradiol protects against the harmful effects of fluoride more by increasing thiol group levels than scavenging hydroxyl radicals.’, Basic Clin Pharmacol Toxicol, 105 (6), 366-73. PubMed: 19799602
Hosur, MB, et al. (2012), ‘Study of thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in subjects with dental fluorosis.’, Eur J Dent, 6 (2), 184-90. PubMed: 22509122
Ortiz-Pérez, D, et al. (2003), ‘Fluoride-induced disruption of reproductive hormones in men.’, Environ Res, 93 (1), 20-30. PubMed: 12865044
Sarkar, SD, R Maiti, and D Ghosh (2006), ‘Management of fluoride induced testicular disorders by calcium and vitamin-E co-administration in the albino rat.’, Reprod Toxicol, 22 (4), 606-12. PubMed: 16769200
Yang, H, et al. (2016), ‘γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice.’, Life Sci, 146 1-7. PubMed: 26724496
Zhou, Y, et al. (2013a), ‘The toxicity mechanism of sodium fluoride on fertility in female rats.’, Food Chem Toxicol, 62 566-72. PubMed: 24071475
Zhou, Y, et al. (2013b), ‘Effects of sodium fluoride on reproductive function in female rats.’, Food Chem Toxicol, 56 297-303. PubMed: 23459146