Abstract
Oxidative stress results from either overproduction of free radicals or insufficiency of several anti-oxidant defense systems. It leads to oxidation of main cellular macromolecules and a resultant molecular dysfunction. Thyroid hormones regulate oxidative metabolism and, thus, play a role in free radical production. Studies evaluating oxidative stress in patients with hypothyroidism and hyperthyroidism have been encountered in recent years; however, oxidative status in patients with euthyroid autoimmune thyroiditis (AIT) was not investigated previously. Thirty-five subjects with euthyroid AIT and 35 healthy controls were enrolled in the study. Serum oxidative status was determined by the measurement of total anti-oxidant status (TAS), total oxidant status (TOS), ischemia-modified albumin (IMA), and oxidized-low density lipoprotein (ox-LDL) levels. Serum TAS levels were significantly lower (p < 0.001), while serum TOS levels and IMA levels were significantly higher (p < 0.001 and p = 0.020, respectively) in patients compared to controls. In both groups, ox-LDL levels were similar (p = 0.608). Serum TAS levels were negatively correlated with anti-thyroid peroxidase and anti-thyroglobulin (anti-TG) levels (rho = −0.415, p = 0.001 and rho = −0.484, p < 0.001, respectively). Serum TOS was positively correlated with anti-TG levels (rho = 0.547, p < 0.001). Further, TAS was positively correlated with free T4 levels (r = 0.279, p = 0.043). No correlation was observed between thyrotropin, free T3 levels, and TOS and TAS levels. These results suggest that oxidants are increased, and anti-oxidants are decreased in patients with euthyroid AIT, and oxidative/anti-oxidative balance is shifted to the oxidative side. Increased oxidative stress might have a role in thyroid autoimmunity.
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References
L. Oziol, P. Faure, N. Bertrand, P. Chomard, Inhibition of in vitro macrophage-induced low density lipoprotein oxidation by thyroid compounds. J. Endocrinol. 177(1), 137–146 (2003)
B. Halliwell, Free radicals, antioxidants and human disease: curiosity, cause or consequence? Lancet 344(8924), 721–724 (1994)
L. Dumitriu, R. Bartoc, H. Ursu, M. Purice, V. Lonescu, Significance of high levels of serum malonyl dialdehyde (MDA) and ceruloplasmin (CP) in hyper- and hypothyroidism. Endocrinologie 26(1), 35–38 (1988)
F. Costantini, S.D. Pierdomenico, D. De Cesare, P. De Remigis, T. Bucciarelli, G. Bittolo-Bon, G. Cazzolato, G. Nubile, M.T. Guanano, S. Sensi, F. Cuccurullo, A. Mezzetti, Effect of thyroid function on LDL oxidation. Arterioscler. Thromb. Vasc. Biol. 18(5), 732–737 (1998)
J.M. Gutteridge, Free radicals in disease processes: a compilation of cause and consequence. Free Radic. Res. Commun. 19(3), 141–158 (1993)
I. Fridovich, Superoxide anion radical (O2-), superoxide dismutases, and related matters. J. Biol. Chem. 272(30), 18515–18517 (1997)
B.S. Berlett, E.R. Stadtman, Protein oxidation in aging, disease and oxidative stress. J. Biol. Chem. 272(33), 20313–20316 (1997)
O. Erel, A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin. Biochem. 37(4), 277–285 (2004)
S.G. Ma, W. Xu, C.L. Wei, X.J. Wu, B. Hong, Z.J. Wang, H.R. Hao, H.Q. Guo, Role of ischemia-modified albumin and total homocysteine in estimating symptomatic lacunar infarction in type 2 diabetic patients. Clin. Biochem. 44(16), 1299–1303 (2011)
S. Turedi, O. Cinar, I. Yavuz, A. Mentese, A. Gunduz, S.C. Karahan, M. Topbas, E. Cevik, A.O. Yildirim, A. Uzun, U. Kaldirim, Differences in ischemia-modified albumin levels between end stage renal disease patients and the normal population. J. Nephrol. 23(3), 335–340 (2010)
C.Y. Chen, W.L. Tsai, P.J. Lin, S.C. Shiesh, The value of serum ischemia-modified albumin for assessing liver function in patients with chronic liver disease. Clin. Chem. Lab. Med. 49(11), 1817–1821 (2011)
D. Bar-Or, G. Curtis, N. Rao, N. Bampos, E. Lau, Characterization of the Co(2+) and Ni(2+) binding amino-acid residues of the N-terminus of human albumin. Eur. J. Biochem. 268(1), 42–47 (2001)
S. Gidenne, F. Ceppa, E. Fontan, F. Perrier, P. Burnat, Analytical performance of the albumin cobalt binding (ACB) test on the Cobas MIRA Plus analyzer. Clin. Chem. Lab. Med. 42(4), 455–461 (2004)
H. Esterbauer, G. Wag, H. Puhl, Lipid peroxidation and its role in atherosclerosis. Br. Med. Bull. 49(3), 566–576 (1993)
D. Steinberg, S. Parthasarathy, T.E. Carew, J.C. Khoo, J.L. Witztum, Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N. Eng. J. Med. 320(14), 915–924 (1989)
A.N. Torun, S. Kulaksizoglu, M. Kulaksizoglu, B.O. Pamuk, E. Isbilen, N.B. Tutuncu, Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clin. Endocrinol. (Oxf) 70(3), 469–474 (2009)
M. Aslan, N. Cosar, H. Celik, N. Aksoy, A.C. Dulger, H. Begenik, Y.U. Soyoral, M.E. Kucukoglu, S. Selek, Evaluation of oxidative status in patients with hyperthyroidism. Endocrine 40(2), 285–289 (2011)
K. Ersoy, İ. Anaforoglu, E. Algün, Serum ischemic modified albumin levels might not be a marker of oxidative stress in patients with hypothyroidism. Endocrine 43(2), 430–433 (2013)
S.G. Ma, L.X. Yang, F. Bai, W. Xu, B. Hong, Ischemia-modified albumin in patients with hyperthyroidism and hypothyroidism. Eur. J. Intern. Med. 23(6), 136–140 (2012)
M. Lampka, R. Junik, A. Nowicka, E. Kopczyńska, T. Tyrakowski, G. Odrowaz-Sypniewska, Oxidative stress markers during a course of hyperthyroidism. Endokrynol. Pol. 57(3), 218–222 (2006)
A. Oge, E. Sozmen, A.O. Karaoglu, Effect of thyroid function on LDL oxidation in hypothyroidism and hyperthyroidism. Endocr. Res. 30(3), 481–489 (2004)
O. Erel, A new automated colorimetric method for measuring total oxidant status. Clin. Biochem. 38(12), 1103–1111 (2005)
D. Bar-Or, E. Lau, J.V. Winkler, A Novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia- a preliminary report. J. Emerg. Med. 19(4), 311–315 (2000)
G. Lippi, M. Montagnana, G.L. Salvagno, G.C. Guidi, Standardization of ischemia-modified albumin testing: adjustment for serum albumin. Clin. Chem. Lab. Med. 45(2), 261–262 (2007)
M.J. Coria, A.I. Pastán, M.S. Gimenez, Serum oxidative stress parameters of women with hypothyroidism. Acta Biomed. 80(2), 135–139 (2009)
H. Erdamar, B. Cimen, H. Gülcemal, R. Saraymen, B. Yerer, H. Demirci, Increased lipid peroxidation and impaired enzymatic antioxidant defense mechanism in thyroid tissue with multinodular goiter and papillary carcinoma. Clin. Biochem. 43(7–8), 650–654 (2010)
L.E. Laatikainen, M.D. Castellone, A. Hebrant, C. Hoste, M.C. Cantisani, J.P. Laurila, G. Salvatore, P. Salerno, F. Basolo, J. Näsman, J.E. Dumont, M. Santoro, M.O. Laukkanen, Extracellular superoxide dismutase is a thyroid differentiation marker down-regulated in cancer. Endocr. Relat. Cancer 17(3), 785–796 (2010)
O. Young, T. Crotty, R. O’Connell, J. O’Sullivan, A.J. Curran, Levels of oxidative damage and lipid peroxidation in thyroid neoplasia. Head Neck 32(6), 750–756 (2010)
E. Carmeli, A. Bachar, S. Barchad, M. Morad, J. Merrick, Antioxidant status in the serum of persons with intellectual disability and hypothyroidism: a pilot study. Res. Dev. Disabil. 29(5), 431–438 (2008)
A. Saad-Hussein, H. Hamdy, H.M. Aziz, H. Mahdy-Abdallah, Thyroid functions in paints production workers and the mechanism of oxidative-antioxidants status. Toxicol. Ind. Health 27(3), 257–263 (2011)
C. Marcocci, L. Bartalena, Role of oxidative stress and selenium in Graves’ hyperthyroidism and orbitopathy. J. Endocrinol. Invest. 36(10 Suppl), 15–20 (2013)
A. Kaur, S. Pandey, S. Kumar, A.A. Mehdi, A. Mishra, Oxidative stress profile in graves’ ophthalmopathy in Indian patients. Orbit 29(2), 97–101 (2010)
B. Pereira, L.F. Rosa, D.A. Safi, E.L. Bechara, R. Curi, Control of superoxide dismutase, catalase and glutathione peroxidase activities in rat lymphoid organs by thyroid hormones. J. Endocrinol. 140(1), 73–77 (1994)
A. Swaroop, T. Ramasarma, Heat exposure and hypothyroid conditions decrease hydrogen peroxide generation in liver mitochondria. Biochem. J. 226(2), 403–408 (1985)
V.S. Reddy, S. Gouroju, M.M. Suchitra, V. Suresh, A. Sachan, P.V. Srinivasa Rao, A.R. Bitla, Antioxidant defense in overt and subclinical hypothyroidism. Horm. Metab. Res. 45(10), 754–758 (2013)
M. Kaçmaz, M. Atmaca, A. Arslan, H. Demir, M.F. Ozbay, Oxidative stress in patients with thyroidectomy and thyroparathyroidectomy under replacement therapy. Endocrine. (2014). doi:10.1007/s12020-014-0270-6
M. Oncel, A. Kıyıcı, S. Onen, Evaluation of the Relationship Between Ischemia-Modified Albumin Levels and Thyroid Hormone Levels. J. Clin. Lab. Anal. (2014). doi:10.1002/jcla.21789
N.I. Krinsky, Mechanism of action of biological antioxidants. Proc. Soc. Exp. Biol. Med. 200(2), 248–254 (1992)
B. Halliwell, J.M. Gutteridge, Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 186, 1–85 (1990)
U. Resch, G. Helsel, F. Tatzber, H. Sinzinger, Antioxidant status in thyroid dysfunction. Clin. Chem. Lab. Med. 40(11), 1132–1134 (2002)
V. Sundaram, A.N. Hanna, L. Koneru, H.A. Newman, J.M. Falko, Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation. J. Clin. Endocrinol. Metab. 82(10), 3421–3424 (1997)
T. Diekman, P.N. Demacker, J.J. Kastelein, A.F. Stalenhoef, W.M. Wiersinga, Increased oxidizability of low-density lipoproteins in hypothyroidism. J. Clin. Endocrinol. Metab. 83(5), 1752–1755 (1998)
B.T. Kurien, H. Scofield, Autoimmunity and oxidatively modified autoantigens. Autoimmun. Rev. 7(7), 567–573 (2008)
D. Shah, N. Mahajan, S. Sah, S.K. Nath, B. Paudyal, Oxidative stress and its biomarkers in systemic lupus erythematosus. J. Biomed. Sci. 21, 23 (2014)
N.C. Laddha, M. Dwivedi, M.S. Mansuri, A.R. Gani, M. Ansarullah, A.V. Ramachandran, S. Dalai, R. Begum, Vitiligo: interplay between oxidative stress and immune system. Exp. Dermatol. 22(4), 245–250 (2013)
B. Zhang, C. Lo, L. Shen, R. Sood, C. Jones, K. Cusmano-Ozog, S. Park-Snyder, W. Wong, M. Jeng, T. Cowan, E.G. Engleman, J.L. Zehnder, The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP. Blood 117(17), 4569–4579 (2011)
M.M. Delmastro, J.D. Piganelli, Oxidative stess and redox modulation potential in type 1 diabetes. Clin. Dev. Immunol. 2011, 593863 (2011)
R. Rostami, M.R. Aghasi, A. Mohammadi, J. Nourooz-Zadeh, Enhanced oxidative stress in Hashimoto’s thyroiditis: inter-relationships to biomarkers of thyroid function. Clin. Biochem. 46(4–5), 308–312 (2013)
G. Vitale, S. Salvioli, C. Franceschi, Oxidative stress and the ageing endocrine system. Nat. Rev. Endocrinol. 9(4), 228–240 (2013)
P. Mitrou, S.A. Raptis, G. Dimitriadis, Thyroid disease in older people. Maturitas 70(1), 5–9 (2011)
C. Duthoit, V. Estienne, A. Giraud, J.M. Durand-Gorde, A.K. Rasmussen, U. Feldt-Rasmussen, P. Carayon, J. Ruf, Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity? Biochem. J. 360(Pt 3), 557–562 (2001)
C.L. Burek, N.R. Rose, Autoimmune thyroiditis and ROS. Autoimmun. Rev. 7(7), 530–537 (2008)
B. Poljsak, D. Suput, I. Milisav, Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid. Med. Cell. Longev. (2013). doi:10.1155/2013/956792
B. Halliwell, The wanderings of a free radical. Free Radic. Biol. Med. 46(5), 531–542 (2009)
K. Schlesier, M. Harwat, V. Böhm, R. Bitsch, Assessment of antioxidant activity by using different in vitro methods. Free Radic. Res. 36(2), 177–187 (2002)
R.L. Prior, G. Cao, In vivo total antioxidant capacity: comparison of different analytical methods. Free Radic. Biol. Med. 27(11–12), 1173–1181 (1999)
D. Wang, J.F. Feng, P. Zeng, Y.H. Yang, J. Luo, Y.W. Yang, Total oxidant/antioxidant status in sera of patients with thyroid cancers. Endocr. Relat. Cancer 18(6), 773–782 (2011)
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This study approved by the local ethical committee (Approval date and number- 26.12.2012/2012-75).
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Baser, H., Can, U., Baser, S. et al. Assesment of oxidative status and its association with thyroid autoantibodies in patients with euthyroid autoimmune thyroiditis. Endocrine 48, 916–923 (2015). https://doi.org/10.1007/s12020-014-0399-3
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DOI: https://doi.org/10.1007/s12020-014-0399-3