Advanced glycation end products (AGEs) are increased in conditions of oxidative stress and promote inflammation by interacting with their receptor RAGE on cell membrane. By contrast, the soluble receptor sRAGE exerts protective effects by competing with RAGE for ligand binding. AGEs/sRAGEs interaction is involved in the pathogenesis of several diseases related to oxidative stress. In the present study, we evaluated the AGEs/sRAGEs oxidative balance in Hashimoto’ thyroiditis (HT).
We measured the levels of sRAGE, by ELISA, and AGEs, by spectrophotometric method, in the serum of 50 HT patients (5 M, 45 F; mean age 38.5 ± 12 years) and 50 age-, sex- and BMI-matched healthy controls. All subjects were euthyroid at recruitment and none was on LT-4 therapy.
Serum sRAGEs were significantly lower (median 424 vs 738 pg/ml; p = 0.001) and AGEs higher (205 vs 114 AU/g prot; p = 0.001) in HT patients compared to controls, and the two parameters were inversely correlated (p = 0.016). Accordingly, the AGEs/sRAGEs ratio was threefold higher in HT patients than controls (0.48 vs 0.15; p = 0.0001). In regression analysis models, serum TPO-Ab were the main predictors for AGEs and sRAGEs levels and AGEs/sRAGEs ratio (p < 0.0001), irrespective of TSH and/or FT4 values.
sRAGEs were decreased and AGEs increased, suggesting a dysregulation of AGE/sRAGEs-related oxidative homeostasis in HT patients, even when in euthyroid status. Autoimmunity per se seems to play an important role in AGEs/sRAGE imbalance, irrespective of thyroid function alterations.
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Kalousová M, Zima T, Tesar V, Dusilová-Sulková S, Skrha J (2005) Advanced glycoxidation end products in chronic diseases—clinical chemistry and genetic background. Mutat Res 579:37–46
Nenna A, Spadaccio C, Lusini M, Ulianich L, Chello M, Nappi F (2015) Basic and clinical research against advanced glycation end products (AGEs): new compounds to tackle cardiovascular disease and diabetic complications. Recent Pat Cardiovasc Drug Discov 10:10–33
Ruggeri RM, Vicchio TM, Cristani M, Certo R, Caccamo D, Alibrandi A, Giovinazzo S, Saija A, Campennì A, Trimarchi F, Gangemi S (2016) Oxidative stress and advanced glycation end products in Hashimoto’s thyroiditis. Thyroid 4:504–511
Ruggeri RM, Cristani M, Vicchio TM, Alibrandi A, Giovinazzo S, Saija A, Campennì A, Trimarchi F, Gangemi S (2019) Increased serum interleukin-37 (IL-37) levels correlate with oxidative stress parameters in Hashimoto’s thyroiditis. J Endocrinol Investig 42:199–205. https://doi.org/10.1007/s40618-018-0903-3
de Groot L, Hinkema H, Westra J, Smit AJ, Kallenberg CG, Bijl M, Posthumus MD (2011) Advanced glycation end products are increased in rheumatoid arthritis patients with controlled disease. Arthritis Res Ther 13:R205
Sternberg Z, Ostrow P, Vaughan M, Chichelli T, Munschauer F (2011) AGE-RAGE in multiple sclerosis brain. Immunol Investig 40:197–205
Alexiou P, Chatzopoulou M, Pegklidou K, Demopoulos VJ (2010) RAGE: a multi-ligand receptor unveiling novel insights in health and disease. Curr Med Chem 17:2232–2252
Wautier MP, Guillausseau PJ, Wautier JL (2017) Activation of the receptor for advanced glycation end products and consequences on health. Diabetes Metab Syndr 11:305–309. https://doi.org/10.1016/j.dsx.2016.09.009
Yang G, Huang Y, Wu X, Lin X, Xu J, Chen X, Bai X, Li Q (2018) Endogenous secretory receptor for advanced glycation end products protects endothelial cells from AGEs induced apoptosis. Biomed Res Int 2018:8216578. https://doi.org/10.1155/2018/8216578
Prasad K, Mishra M (2018) AGE-RAGE stress, stressors, and antistressors in health and disease. Int J Angiol 27:1–12. https://doi.org/10.1055/s-0037-1613678
Corica D, Aversa T, Ruggeri RM, Cristani M, Alibrandi A, Pepe G, De Luca F, Wasniewska M (2019) Could AGE/RAGE-related oxidative homeostasis dysregulation enhance susceptibility to pathogenesis of cardio-metabolic complications in childhood obesity? Front Endocrinol 10:426. https://doi.org/10.3389/fendo.2019.00426
Caturegli P, De Remigis A, Rose NR (2014) Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun Rev 13:391–397
Aslan M, Cosar N, Celik H, Aksoy N, Dulger AC, Begenik H, Soyoral YU, Kucukoglu ME, Selek S (2011) Evaluation of oxidative status in patients with hyperthyroidism. Endocrine 40:285–289
Baser H, Can U, Baser S, Yerlikaya FH, Aslan U, Hidayetoglu BT (2014) Assessment of oxidative status and its association with thyroid autoantibodies in patients with euthyroid autoimmune thyroiditis. Endocrine 48:916–923
Reddy SV, Suchitra MM, Pradeep V, Alok S, Suresh V, Bitla AR, Srinivasa Rao PV (2015) Ischemia-modified albumin levels in overt and subclinical hypothyroidism. J Endocrinol Investig 38:885–890
Ates I, Yilmaz FM, Altay M, Yilmaz N, Berker D, Güler S (2015) The relationship between oxidative stress and autoimmunity in Hashimoto’s thyroiditis. Eur J Endocrinol 173:791–799
Korkmaz H, Tabur S, Ozkaya M, Oguz E, Aksoy N, Akarsu E (2015) Serum prolidase levels in Graves’ disease without ophthalmopathy and its association with oxidative status. J Endocrinol Investig 11:1167–1173
Rotondo Dottore G, Ionni I, Menconi F, Casini G, Sellari-Franceschini S, Nardi M, Vitti P, Marcocci C, Marinò M (2018) Antioxidant effects of β-carotene, but not of retinol and vitamin E, in orbital fibroblasts from patients with Graves’ orbitopathy (GO). J Endocrinol Investig 41:815–820. https://doi.org/10.1007/s40618-017-0809-5
Ye J, Zhong X, Du Y, Cai C, Pan T (2017) Role of levothyroxine and vitamin E supplementation in the treatment of oxidative stress-induced injury and apoptosis of myocardial cells in hypothyroid rats. J Endocrinol Investig 40:713–719
Karimi F, Omrani GR (2019) Effects of selenium and vitamin C on the serum level of antithyroid peroxidase antibody in patients with autoimmune thyroiditis. J Endocrinol Investig 42:481–487. https://doi.org/10.1007/s40618-018-0944-7
Caspar-Bell G, Dhar I, Prasad K (2016) Advanced glycation end products (AGEs) and its receptors in the pathogenesis of hyperthyroidism. Mol Cell Biochem 414:171–178. https://doi.org/10.1007/s11010-016-2669-2
Peng S, Li C, Wang X, Liu X, Han C, Jin T, Liu S, Zhang X, Zhang H, He X, Xie X, Yu X, Wang C, Shan L, Fan C, Shan Z, Teng W (2016) Increased toll-like receptors activity and TLR ligands in patients with autoimmune thyroid diseases. Front Immunol 7:578. https://doi.org/10.3389/fimmu.2016.00578
Tsan MF, Gao B (2004) Endogenous ligands of toll-like receptors. J Leukoc Biol 76:514–519
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Ruggeri, R.M., Barbalace, M.C., Cristani, M.T. et al. Serum levels of advanced glycation end products (AGEs) are increased and their soluble receptor (sRAGE) reduced in Hashimoto’s thyroiditis. J Endocrinol Invest 43, 1337–1342 (2020). https://doi.org/10.1007/s40618-020-01231-7
- Hashimoto’s thyroiditis
- Oxidative stress
- Advanced glycation end products (AGEs)
- soluble Advanced Glycation End Products Receptor (sRAGE)