Cadmium Effects on Thyroid Gland & Function

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Cadmium Effects on Thyroid Gland & Function

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Buha A, Matovic V, Antonijevic B, et al - "Overview of Cadmium Thyroid Disrupting Effects and Mechanisms" Int J Mol Sci 19(5):1501 (2018) doi:10.3390/ijms19051501

Buha A, Antonijević B, Bulat Z, Jaćević V, Milovanović V, Matović V - "The impact of prolonged cadmium exposure and co-exposure with polychlorinated biphenyls on thyroid function in rats" Toxicol Lett ;221(2):83-90 (2013)
doi: 10.1016/j.toxlet.2013.06.216. Epub 2013 Jun 21. PubMed PMID: 23792431. ... t=abstract
"Thyroid hormones were adversely affected by cadmium, with most prominent effect observed on triiodothyroxine levels indicating Cd interference with thyroid function at extrathyroidal level. "

Caride A - "Cadmium chronotoxicity at pituitary level: effects on plasma ACTH, GH, and TSH daily pattern" J Physiol Biochem 66(3):213-20 (2010)

Hammouda F - "Reversal of cadmium-induced thyroid dysfunction by selenium, zinc, of their combination in rat" Biol Trace Elem Res 126(1-3):194-203 (2008)
Increase in TSH, lower serum T4

Jancic SA , Stosic BZ - "Cadmium effects on the thyroid gland" Vitam Horm 94:391-425 (2014)
  • Cadmium has been listed as one of the 126 priority pollutants and a category I carcinogen. Carcinogenic effects of cadmium on the lungs, testicles, and prostate are widely recognized, but there has been insufficient research on the effect of cadmium on the thyroid gland. Cadmium has the affinity to accumulate not only in the liver, kidneys, and pancreas but also in the thyroid gland. It has been established that cadmium blood concentration correlates positively with its accumulation in the thyroid gland. Women of fertile age have higher cadmium blood and urine concentrations than men. In spite of its redox inertia, cadmium brings about oxidative stress and damage to the tissue by indirect mechanisms. Mitochondria are considered to be the main intracellular targets for cadmium. Colloid cystic goiter, adenomatoid follicular hyperplasia with low-grade dysplasia and thyroglobulin hypo- and asecretion, and parafollicular cell diffuse and nodular hyperplasia and hypertrophy are often found in chronic cadmium toxicity.
Li ZH, Chen L, Wu YH, Li P, Li YF, Ni ZH - "Effects of waterborne cadmium on thyroid hormone levels and related gene expression in Chinese rare minnow larvae" Comp Biochem Physiol C Toxicol Pharmacol 161:53-7 (2014) doi:10.1016/j.cbpc.2014.02.001. Epub 2014 Feb 9. PubMed PMID: 24521933.

Li J, Liu Y, Kong D, Ren S, Li N - "T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc" Environ Sci Pollut Res Int 23(10):9843-51 (2016) doi: 10.1007/s11356-016-6095-5. Epub 2016 Feb 9.

Ling HT, Huang R, Liang XX, Li ZX, Wang J, Tan JB, Wu SX, Wang P, Chen ZH, Huang Q, Lyu YJ, Jiang Q, Yang XF, Wu YN - "Long-term effect of environmental cadmium exposure on human body's mineral metabolic balance" Zhonghua Yu Fang Yi Xue Za Zhi 50(4):316-21 (2016)
doi: 10.3760/cma.j.issn.0253-9624.2016.04.007.

Paier B, Hagmüller K, Noli MI, Gonzalez Pondal M, Stiegler C, Zaninovich AA - "Changes induced by cadmium administration on thyroxine deiodination and sulfhydryl groups in rat liver" J Endocrinol 138(2):219-24 (1993)
  • The effects of cadmium on 5'-deiodination of thyroxine (T4) by rat liver and on the hepatic concentration of non-protein sulfhydryl groups (NPSH) were studied in Wistar rats of 200-250 g body weight. A group of ten rats was injected with cadmium chloride (300 micrograms/100 g body weight i.p.) daily for 4 days. Another group of six rats received, in addition, dithiothreitol (DTT; 1 mg/100 g body weight i.p.) daily for the same period. A group of eight normal untreated rats served as control. T4 deiodination was also determined in aliquots of liver from untreated rats, with cadmium (2 or 5 mmol/l) and with or without DTT (0, 2.5, 5 or 10 mmol/l) plus 1 microCi 125I-labelled T4. Hepatic NPSH were measured by a colorimetric method employing dithioldinitrobenzoic acid. Homogenates were incubated for 90 min at 37 degrees C and chromatographed in a tertiary amyl alcohol:hexane:ammonia (2 mol/l) (10:1:12) system. Cadmium-injected rats showed a significant (P < 0.01) decrease in T4 deiodination and in the generation of 125I (P < 0.01) and tri-iodothyronine (T3) (P < 0.02). NPSH were also decreased (P <0.02). Administration of DTT restored T4 deiodination and NPSH to normal. In-vitro addition of cadmium or DTT to normal rat liver homogenates induced similar effects on the degradation of T4. Serum concentrations of T4 (P < 0.01) and T3 (P < 0.01) declined significantly in cadmium-injected rats, whereas DTT administration failed to normalize serum hormone levels. The data suggest that cadmium may have decreased 5' deiodinating activity through binding to sulfhydryl groups of 5'-deiodinase as it does in other enzymes.
Mohammed TM -"Effects of phytate on thyroid gland of rats intoxicated with cadmium" Toxicol Ind Health (2013)

Paier B, Pavia MA Jr, Hansi C, Noli MI, Hagmüller K, Zaninovich AA - "Cadmium inhibits the in vitro conversion of thyroxine to triiodothyronine in rat brown adipose tissue" Bull Environ Contam Toxicol. 59(1):164-70 (1997)

Brown adipose tissue (BAT) thermogenesis during cold exposure in the rat is stimulated by noradrenaline (NA) activation of the synthesis of several enzymes essential for heat production and dissipation (see reviews Nichols and Locke 1984; Himms-Hagen 1990). One of the enzymes is 5’-deiodinase, whose activity in the cold increases by several-fold resulting in an increased T4 to T3 deiodination in BAT (Silva and Larsen 1985). Augmented T3 production has been considered an important step in BAT response to cold, since deiodination of T4 to T3 optimizes NA activation of gene expression of the uncoupling protein (UCP), a protein crucial for uncoupling mitochondrial respiration to produce heat (Bianco and Silva 1987). In a previous study (Cageao et al. 1995) we observed that hypothyroid rats had a pronounced decrease of (3H)guanosine-5’-diphosphate (GDP) binding to BAT mitochondrial proteins. This change reflected a diminished UCP concentration which follows the lack of thyroid hormones (Bianco and Silva 1987). Cadmium has been shown to inhibit the in vitro conversion of T4 to T3 in several tissues (Yoshida et al. 1987; Paier et al. 1993; Pavia et al. 1997). Given the significance of BAT T3 production in thermogenesis, the present study set out to investigate the effects of cadmium on the in vitro conversion of T4 to T3 in BAT from cold-exposed and control rats.

Pavia Júnior MA - "Evidence suggesting that cadmium induces a non-thyroidal illness syndrome in the rat" J Endocrinol 154(1):113-7 (1997)
Increase in TSH around the clock

Rosati MV, Montuori L, Caciari T, Sacco C, Marrocco M, Tomei G, Scala B, Sancini A, Anzelmo V, Bonomi S, Tomei F - "Correlation between urinary cadmium and thyroid hormones in outdoor workers exposed to urban stressors" Toxicol Ind Healthpii: 0748233715602833 (2015) ... ormat=text
  • OBJECTIVES: The aim of this study is to evaluate whether exposure to low concentrations of cadmium (Cd) can have effects on the thyroid hormone level of outdoor workers exposed to urban pollutants.

    METHODS: The study was conducted on a final sample of 277 individuals (184 males and 93 females). The environmental monitoring of Cd was evaluated through the use of portable dosimeters, while the biological monitoring was achieved through the assessment of urinary Cd and thyroid hormones. The total sample was divided according to sex and task. The Pearson's correlation coefficient among the variables was calculated after subdivision on the basis of sex and task. The multiple linear regression was performed to take into account the major confounding factors.

    RESULTS: Statistical tests showed a negative correlation between urinary Cd levels and free triiodothyronine and free thyroxine and a positive correlation between urinary Cd and thyroid-stimulating hormone levels.

    CONCLUSIONS: Our early results seem to point out that occupational exposure to low concentrations of Cd present in urban air affects the thyroid hormone levels in exposed workers.
Yoshida K, Sugihira N, Suzuki M, Sakurada T, Saito S, Yoshinaga K, Saito H - "Effect of cadmium on T4 outer ring monodeiodination by rat liver" Environ Res 42(2):400-5 (1987)
  • The effect of cadmium on thyroxine (T4) outer ring monodeiodination was studied in vivo and in vitro in the rat liver. One microgram of T4 was incubated with rat liver homogenates in 50 mM Tris--HCl buffer, pH 7.4, with or without 0.5, 5, and 50 mM dithiothreitol (DTT) for 60 min in the presence of 10(-8) to 10(-3) M CdCl2, and the amount of 3,5,3'-triiodothyronine (T3) produced was determined by a specific radioimmunoassay. Subcutaneous injection of CdCl2, 1 mg/kg BW/day, 5 days a week for 10 weeks, to the rats resulted in a significant reduction in serum T3 concentration (by 37%) and hepatic T3 production from T4 (by 78 to 92%). In vitro addition of 1 microM to 1 mM CdCl2 to liver homogenates caused a concentration-dependent reduction in T3 generation. Without DTT a 50% reduction in the T4 to T3 converting activity was caused by 4 X 10(-6) M CdCl2. DTT (0.5 to 50 mM) partially restored T3 generation roughly in a concentration-dependent manner. These results indicate that cadmium has some effects on the metabolism of thyroid hormone.
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