OXIDATIVE STRESS IN HUMAN THYROID GLAND UNDER IODINE DEFICIENCY NODULAR GOITER: FROM HARMLESSNESS TO HAZARD DEPENDING ON COPPER AND IODINE SUBCELLULAR DISTRIBUTION

H Falfushynska,A Shulgai,L Gnatyshyna,O Stoliar,V Shidlovski

doi:10.11603/ijmmr.2413-6077.2015.1.2822

Abstract

Background. Thyroid disorders are the second most common endocrinopathies found in humans and animals. Determination of their key molecular markers presents a special interest. Objective. We studied iodine and copper accumulation in nodular, paranodular and contralateral (not affected tissue by node) tissues of human thyroid gland in relation to the level of metal-binding proteins, potential antioxidants, and oxidative changes in tissue for this goal. Lower level of organificated iodine and higher level and mass fraction of inorganic iodine and copper in the nodular and paranodular tissue versus contralateral part of thyroid gland was established. Results. The level of both metal-binding and apo-form of metallothioneins was higher. Content of reduced glutathione was lower in node-affected tissue compared to the contralateral part. Signs of oxidative stress (higher activity of superoxide dismutase, catalase, glutathione-transferase and level of oxyradicals) and cytotoxicity (higher cathepsin D activity, higher level of DNA strand breaks and glycolysis activation) in affected tissue were observed. The range of indice variability in paranodular tissue was smaller than in nodule compared to the parenchyma of contralateral part. Conclusions. Excess of copper unbound to metallothionein in goitrous-changed tissue and high level of inorganic iodine could be the reason for elevated DNA fragmentation and increased lysosomal membrane permeability and activation of antioxidant defense. The main criterions of goiter formation were represented by low level of organificated iodine and high level of DNA damage in thyroid gland.KEY WORDS: iodine deficiency nodular colloidal goiter, iodine, copper, metallothioneins, oxidative stress, cytotoxicity

Highlights

Thyroid disorders are the second most common endocrinopathies found in humans and animals [1]
Excess of copper unbound to metallothionein in goitrous-changed tissue and high level of inorganic iodine could be the reason for elevated DNA fragmentation and increased lysosomal membrane permeability and activation of antioxidant defense
The results showed the coherent activation of superoxide dismutase, catalase and glutathione-transferase, decrease of GSH level and the increase of metallothioneins level in affected part of thyroid gland (Fig. 1, 2)

Summary

Introduction

Thyroid disorders are the second most common endocrinopathies found in humans and animals [1]. Iodine deficiency in thyroid pathology occurrence rate is rapidly increasing [2] It has miscellaneous origins as a result of complex interaction of endogenous and exogenous factors and arises in the setting of high level of “nonspecific” goitrogens, among them copper, in the environment. Copper is an essential element for humans and animals, especially for antioxidant defense and the metabolism of the amino acid tyrosine, which is needed for the production of thyroid hormones [3]. Besides these ones, excessive amounts of copper in the body can pose a risk. Thyroid disorders are the second most common endocrinopathies found in humans and animals Determination of their key molecular markers presents a special interest

Methods

Results

Discussion

Conclusion