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Serum levels of advanced glycation end products (AGEs) are increased and their soluble receptor (sRAGE) reduced in Hashimoto’s thyroiditis

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Abstract

Purpose

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).

Methods

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.

Results

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.

Conclusion

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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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    R. M. Ruggeri & G. Giuffrida

  2. Endocrine Unit, University Hospital AOU Policlinico G. Martino, 98125, Messina, Italy

    R. M. Ruggeri, S. Giovinazzo, G. Giuffrida & S. Cannavò

  3. Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, Bologna, Italy

    M. C. Barbalace

  4. Department of Pharmaceutical Sciences and Health Products, University of Messina, Messina, Italy

    M. T. Cristani

  5. Unit of Statistical and Mathematical Sciences, Department of Economics, University of Messina, Messina, Italy

    A. Alibrandi

  6. Accademia Peloritana dei Pericolanti, University of Messina, Messina, Italy

    F. Trimarchi

  7. Department of Human Pathology DETEV, University of Messina, Messina, Italy

    S. Cannavò

  8. Unit of Nuclear Medicine, Department of Biomedical Sciences and Morphological and Functional Images, University of Messina, Messina, Italy

    A. Campennì

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  1. R. M. Ruggeri
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Correspondence to R. M. Ruggeri.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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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

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  • DOI: https://doi.org/10.1007/s40618-020-01231-7

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