Abstract
Selenium (Se), an important oligoelement, is a component of the antioxidant system. Over the last decade, it has been ever more frequently discussed in the context of thyroid disorders. Graves’ disease and Hashimoto’s thyroiditis, differentiated thyroid cancer, and even endemic goiter may have common triggers that are activated by excess reactive oxygen species (ROS), which are involved in various stages of the pathogenesis of thyroid disorders. Most oxidative events occur in mitochondria, organelles that contain enzymes with Se as a cofactor. Mitochondria are responsible for the production of ATP in the cell and are also a major site of ROS production. Thyroid hormone status (the thyroid being the organ with the highest concentration of Se in the body) has a profound impact on mitochondria biogenesis. In this review, we focus on the role of Se in mitochondrial function in thyroid disorders with impaired oxidative stress, since both thyroid hormone synthesis and thyroid dysfunction involve ROS. The role of Se deficiency or its excess in relation to mitochondrial dysfunction in the context of thyroid disorders is therefore of interest.
Similar content being viewed by others
References
Rizzo AM, Berselli P, Zava S, Montorfano G, Negroni M, Corsetto P, Berra B (2010) Endogenous antioxidants and radical scavengers. Adv Exp Med Biol 698:52–67
Di MS, Reed TT, Venditti P, Victor VM (2016) Role of ROS and RNS sources in physiological and pathological conditions. Oxidative Med Cell Longev 2016:1245049
Duntas LH, Benvenga S (2015) Selenium: an element for life. Endocrine 48:756–775
Wallenberg M, Misra S, Bjornstedt M (2014) Selenium cytotoxicity in cancer. Basic Clin Pharmacol Toxicol 114:377–386
Kurokawa S, Takehashi M, Tanaka H, Mihara H, Kurihara T, Tanaka S, Hill K, Burk R, Esaki N (2011) Mammalian selenocysteine lyase is involved in selenoprotein biosynthesis. J Nutr Sci Vitaminol (Tokyo) 57:298–305
Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443
Labunskyy VM, Hatfield DL, Gladyshev VN (2014) Selenoproteins: molecular pathways and physiological roles. Physiol Rev 94:739–777
Schomburg L (2011) Selenium, selenoproteins and the thyroid gland: interactions in health and disease. Nat Rev Endocrinol 8:160–171
Valea A, Georgescu CE (2018) Selenoproteins in human body: focus on thyroid pathophysiology. Hormones (Athens ) 17:183–196
Biesalski HK (2002) Meat and cancer: meat as a component of a healthy diet. Eur J Clin Nutr 56(Suppl 1):S2–S11
Faria CC, Peixoto MS, Carvalho DP, Fortunato RS (2019) The emerging role of estrogens in thyroid redox homeostasis and carcinogenesis. Oxidative Med Cell Longev 2019:2514312
Schweizer U, Chiu J, Kohrle J (2008) Peroxides and peroxide-degrading enzymes in the thyroid. Antioxid Redox Signal 10:1577–1592
Szanto I, Pusztaszeri M, Mavromati M (2019) H2O2 metabolism in normal thyroid cells and in thyroid tumorigenesis: focus on NADPH oxidases. Antioxidants (Basel) 8
Lushchak VI (2014) Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol Interact 224:164–175
Ghaddhab C, Kyrilli A, Driessens N, Van Den Eeckhaute E, Hancisse O, De Deken X, Dumont JE, Detours V, Miot F, Corvilain B (2019) Factors contributing to the resistance of the thyrocyte to hydrogen peroxide. Mol Cell Endocrinol 481:62–70
Maouche N, Meskine D, Alamir B, Koceir EA (2015) Trace elements profile is associated with insulin resistance syndrome and oxidative damage in thyroid disorders: manganese and selenium interest in Algerian participants with dysthyroidism. J Trace Elem Med Biol 32:112–121
Ylikallio E, Suomalainen A (2012) Mechanisms of mitochondrial diseases. Ann Med 44:41–59
Di DG, Hirshberg J, Lyle D, Freij JB, Caturegli P (2016) Reactive oxygen species in organ-specific autoimmunity. Auto Immun Highlights 7:11
Wesselink E, Koekkoek WAC, Grefte S, Witkamp RF, van Zanten ARH (2018) Feeding mitochondria: potential role of nutritional components to improve critical illness convalescence. Clin Nutr
Harrois A, Huet O, Duranteau J (2009) Alterations of mitochondrial function in sepsis and critical illness. Curr Opin Anaesthesiol 22:143–149
Selivanov VA, Votyakova TV, Pivtoraiko VN, Zeak J, Sukhomlin T, Trucco M, Roca J, Cascante M (2011) Reactive oxygen species production by forward and reverse electron fluxes in the mitochondrial respiratory chain. PLoS Comput Biol 7:e1001115
Liemburg-Apers DC, Willems PH, Koopman WJ, Grefte S (2015) Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Arch Toxicol 89:1209–1226
Galley HF (2011) Oxidative stress and mitochondrial dysfunction in sepsis. Br J Anaesth 107:57–64
Cline SD (2012) Mitochondrial DNA damage and its consequences for mitochondrial gene expression. Biochim Biophys Acta 1819:979–991
Forini F, Nicolini G, Kusmic C, Iervasi G (2019) Protective effects of euthyroidism restoration on mitochondria function and quality control in cardiac pathophysiology. Int J Mol Sci 20
de Castro AL, Tavares AV, Fernandes RO, Campos C, Conzatti A, Siqueira R, Fernandes TR, Schenkel PC, Sartorio CL, Llesuy S, Bello-Klein A, da Rosa Araujo AS (2015) T3 and T4 decrease ROS levels and increase endothelial nitric oxide synthase expression in the myocardium of infarcted rats. Mol Cell Biochem 408:235–243
Forini F, Nicolini G, Kusmic C, D'Aurizio R, Rizzo M, Baumgart M, Groth M, Doccini S, Iervasi G, Pitto L (2018) Integrative analysis of differentially expressed genes and miRNAs predicts complex T3-mediated protective circuits in a rat model of cardiac ischemia reperfusion. Sci Rep 8:13870
Xu M, Wang Y, Ayub A, Ashraf M (2001) Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential. Am J Physiol Heart Circ Physiol 281:H1295–H1303
Chi HC, Tsai CY, Tsai MM, Yeh CT, Lin KH (2019) Molecular functions and clinical impact of thyroid hormone-triggered autophagy in liver-related diseases. J Biomed Sci 26:24
Yau WW, Singh BK, Lesmana R, Zhou J, Sinha RA, Wong KA, Wu Y, Bay BH, Sugii S, Sun L, Yen PM (2019) Thyroid hormone (T3) stimulates brown adipose tissue activation via mitochondrial biogenesis and MTOR-mediated mitophagy. Autophagy 15:131–150
Mehta SL, Kumari S, Mendelev N, Li PA (2012) Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. BMC Neurosci 13:79
Cheng SY, Leonard JL, Davis PJ (2010) Molecular aspects of thyroid hormone actions. Endocr Rev 31:139–170
de Vries EM, Fliers E, Boelen A (2015) The molecular basis of the non-thyroidal illness syndrome. J Endocrinol 225:R67–R81
Berger MM, Lemarchand-Beraud T, Cavadini C, Chiolero R (1996) Relations between the selenium status and the low T3 syndrome after major trauma. Intensive Care Med 22:575–581
Schomburg L, Riese C, Michaelis M, Griebert E, Klein MO, Sapin R, Schweizer U, Kohrle J (2006) Synthesis and metabolism of thyroid hormones is preferentially maintained in selenium-deficient transgenic mice. Endocrinology 147:1306–1313
Angstwurm MW, Schopohl J, Gaertner R (2004) Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients. Eur J Endocrinol 151:47–54
Manzanares W, Lemieux M, Elke G, Langlois PL, Bloos F, Heyland DK (2016) High-dose intravenous selenium does not improve clinical outcomes in the critically ill: a systematic review and meta-analysis. Crit Care 20:356
Olivieri O, Girelli D, Stanzial AM, Rossi L, Bassi A, Corrocher R (1996) Selenium, zinc, and thyroid hormones in healthy subjects: low T3/T4 ratio in the elderly is related to impaired selenium status. Biol Trace Elem Res 51:31–41
McLachlan SM, Aliesky H, Banuelos B, Hee SSQ, Rapoport B (2017) Variable effects of dietary selenium in mice that spontaneously develop a spectrum of thyroid autoantibodies. Endocrinology 158:3754–3764
Brcic L, Baric A, Gracan S, Torlak V, Brekalo M, Skrabic V, Zemunik T, Barbalic M, Punda A, Boraska PV (2019) Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto’s thyroiditis. Sci Rep 9:5360
Duthoit C, Estienne V, Giraud A, Durand-Gorde JM, Rasmussen AK, Feldt-Rasmussen U, Carayon P, Ruf J (2001) Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity? Biochem J 360:557–562
Niethammer P, Grabher C, Look AT, Mitchison TJ (2009) A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 459:996–999
Duntas LH (2015) The role of iodine and selenium in autoimmune thyroiditis. Horm Metab Res 47:721–726
Ates I, Yilmaz FM, Altay M, Yilmaz N, Berker D, Guler S (2015) The relationship between oxidative stress and autoimmunity in Hashimoto’s thyroiditis. Eur Fed Endocr Soc 173(6):791–799. https://doi.org/10.1530/EJE-15-0617
Baser H, Can U, Baser S, Yerlikaya FH, Aslan U, Hidayetoglu BT (2015) Assessment of oxidative status and its association with thyroid autoantibodies in patients with euthyroid autoimmune thyroiditis. Endocrine 48:916–923
Ruggeri RM, Vicchio TM, Cristani M, Certo R, Caccamo D, Alibrandi A, Giovinazzo S, Saija A, Campenni A, Trimarchi F, Gangemi S (2016) Oxidative stress and advanced glycation end products in Hashimoto’s thyroiditis. Thyroid 26:504–511
Pritchard J, Han R, Horst N, Cruikshank WW, Smith TJ (2003) Immunoglobulin activation of T cell chemoattractant expression in fibroblasts from patients with Graves’ disease is mediated through the insulin-like growth factor I receptor pathway. J Immunol 170:6348–6354
Marcocci C, Bartalena L (2013) Role of oxidative stress and selenium in Graves’ hyperthyroidism and orbitopathy. J Endocrinol Investig 36:15–20
Duntas LH (2012) The evolving role of selenium in the treatment of Graves’ disease and ophthalmopathy. J Thyroid Res 2012:736161
Teixeira RB, Fernandes-Piedras TRG, Bello-Klein A, Carraro CC, Araujo ASDR (2019) An early stage in T4-induced hyperthyroidism is related to systemic oxidative stress but does not influence the pentose cycle in erythrocytes and systemic inflammatory status. Arch Endocrinol Metab
Komosinska-Vassev K, Olczyk K, Kucharz EJ, Marcisz C, Winsz-Szczotka K, Kotulska A (2000) Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves’ disease during therapy. Clin Chim Acta 300:107–117
Kocak M, Akarsu E, Korkmaz H, Taysi S (2019) The effect of antithyroid drugs on osteopontin and oxidative stress in Graves’ disease. Acta Endocrinol (Buchar ) 15:221–224
Ademoglu E, Ozbey N, Erbil Y, Tanrikulu S, Barbaros U, Yanik BT, Bozbora A, Ozarmagan S (2006) Determination of oxidative stress in thyroid tissue and plasma of patients with Graves’ disease. Eur J Intern Med 17:545–550
Kihara M, Kontani K, Yamauchi A, Miyauchi A, Nakamura H, Yodoi J, Yokomise H (2005) Expression of thioredoxin in patients with Graves’ disease. Int J Mol Med 15:795–799
Choi W, Li Y, Ji YS, Yoon KC (2018) Oxidative stress markers in tears of patients with Graves’ orbitopathy and their correlation with clinical activity score. BMC Ophthalmol 18:303
Ursu HI, Badiu C, Gheorghiu ML (2012) Selenium, mild Graves ophtalmopathy and current smoking status. Acta Endo (Buc) 8:467–470
Zhang F, Yu W, Hargrove JL, Greenspan P, Dean RG, Taylor EW, Hartle DK (2002) Inhibition of TNF-alpha induced ICAM-1, VCAM-1 and E-selectin expression by selenium. Atherosclerosis 161:381–386
Li YB, Han JY, Jiang W, Wang J (2011) Selenium inhibits high glucose-induced cyclooxygenase-2 and P-selectin expression in vascular endothelial cells. Mol Biol Rep 38:2301–2306
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40
Bhattacharjee A, Basu A, Sen T, Biswas J, Battacharya S (2017) Nano-Se as a novel candidate in the management of oxidative stress related disorders and cancer. Nucleus:137–145
Kong L, Yuan Q, Zhu H, Li Y, Guo Q, Wang Q, Bi X, Gao X (2011) The suppression of prostate LNCaP cancer cells growth by selenium nanoparticles through Akt/Mdm2/AR controlled apoptosis. Biomaterials 32:6515–6522
Lee KH, Jeong D (2012) Bimodal actions of selenium essential for antioxidant and toxic pro-oxidant activities: the selenium paradox (review). Mol Med Rep 5:299–304
Cao TM, Hua FY, Xu CM, Han BS, Dong H, Zuo L, Wang X, Yang Y, Pan HZ, Zhang ZN (2006) Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells. Ann Hematol 85:434–442
Collery P (2018) Strategies for the development of selenium-based anticancer drugs. J Trace Elem Med Biol 50:498–507
Negro R, Hegedus L, Attanasio R, Papini E, Winther KH (2019) A 2018 European thyroid association survey on the use of selenium supplementation in Graves’ hyperthyroidism and Graves’ orbitopathy. Eur Thyroid J 8:7–15
Acknowledgments
The authors would like to thank Prof. Leonidas Duntas for his constructive criticism and scientific guidance in the elaboration of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Gheorghiu, M.L., Badiu, C. Selenium involvement in mitochondrial function in thyroid disorders. Hormones 19, 25–30 (2020). https://doi.org/10.1007/s42000-020-00173-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42000-020-00173-2