Introductory Chapter: The Relationship between Hyperthyroidism and Oxidative Stress-Mediated Cell Damage

1. Introduction

Oxidative stress describes the pathological condition that occurs as a result of the reaction of reactive oxygen species with various biomolecules in the organism [1]. It may occur as a result of the increase of free oxygen radicals in the body and the synthesis of nitric oxide [2, 3]. The free radicals formed combine with the DNA, carbohydrates, lipids, and proteins in the cell and cause the cell structure to deteriorate [4, 5, 6]. In addition, lipid peroxidation occurs as a result of the reaction of lipids in the cell membrane with free radicals [7]. MDA, the intermediate product of this reaction, is formed [8]. MDA formation is directly proportional to the cell membrane’s damage and irreversible damage [9]. Free radicals cause DNA double helix cleavage and nucleic acid base exchange, thus making DNA ready for mutation [10, 11]. Again, free radicals cause protein oxidation [12]. As a result of this reaction, the function of the proteins is impaired and the enzymatic reactions in which the proteins take part, the transport systems, and the functions of the receptors are impaired [13]. In addition, reactive oxygens oxidize monosaccharides to form oxoaldehydes, which cross-link with DNA and RNA [14]. This leads to cancer and aging. In addition, reactive oxygen species cause the destruction of immune system cells, thus weakening the immune system [15]. There are some antioxidant-effective enzymes as a protective system in the organism against this damage [16]. They protect the cell from oxidative stress by scavenging free oxygen radicals or reducing their effects [17]. Antioxidants are divided into two groups, enzymatic and non-enzymatic. While antioxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), peroxidase, and glutathione reductase (GR) are classified as enzymatic, GSH, vitamin C, urate, bilirubin, albumin, ceruloplasmin, transferrin, and lactoferrin are classified as non-enzymatic [18, 19, 20]. Thyroid hormones increase the metabolic activity of tissues in most living organisms [21, 22]. Thyroid hormones show their effect on energy metabolism, oxygen consumption, and some mitochondrial functions including oxidative phosphorylation, and by increasing mitochondrial respiration by making many changes in the activity and number of some mitochondrial respiratory chain components [23, 24]. With the effectiveness of thyroid hormones, superoxide formation in the mitochondrial electron transport system increases [25]. As a result of this increase, oxidative stress and cell damage occur [26]. The metabolic effects of thyroid hormones are well known, but the effects of thyroid hormone deficiency and excess on lipid peroxidation and antioxidant system have not been clearly demonstrated [27, 28]. In this section, we aimed to explain the mechanism of the relationship between hyperthyroidism and oxidative stress-mediated cell damage.

2. Hyperthyroidism and oxidative stress

Hyperthyroidism is defined as excessive secretion of thyroid hormones. Thyroid hormones increase basal metabolism and thus oxidative metabolism by inducing specific mitochondrial enzymes [29]. Therefore, hyperthyroidism accelerates the formation of free oxygen radicals and causes evenings in the antioxidant defense system [30] (Figure 1). As a result of increased free radical formation in patients with hyperthyroidism, changes in the concentrations of other related molecules (antioxidants, lipid peroxides) are expected [31]. It has been stated that there may be a relationship between the physiopathology of this disease and free radicals and antioxidants [32]. Defects in the antioxidant enzyme system can lead to the accumulation of reactive oxygen derivatives [33]. ROS targets protein oligosaccharides and alters their biological functions [34]. Due to oxidative stress, the extracellular matrix glycosaminoglycan structure is destroyed [35]. Hydrogen peroxide, formed due to the catalysis of superoxide ions by superoxide dismutase, is used as a substrate for thyroid hormone synthesis by thyroid peroxidase [36]. In a study, it was reported that the GSH level was significantly reduced in patients with hyperthyroidism [37]. Again, some studies determined that MDA levels increased in various tissues of patients with hyperthyroidism, and SOD activity decreased [38]. Thyroid hormones cause a hypermetabolic state by changing the activity and number of mitochondrial respiratory chain components and increasing the mitochondrial respiratory rate. The accelerated mitochondrial electron transport also increases the formation of superoxide, and in this way, the formation of many reactive species occurs [39]. As a result of oxidative stress and impaired antioxidant defense mechanism, cell membranes and organelles are damaged.

Figure 1.

Hyperthyroidism and oxidative stress.

3. Conclusion

As a result, hyperthyroidism is a pathological condition that occurs as a result of excessive secretion of thyroid hormone. In the case of hyperthyroidism, the increased thyroid hormone level causes an increase in the metabolic activity of the tissues. Particularly with the effectiveness of thyroid hormones, superoxide formation in the mitochondrial electron transport system increases. Increasing metabolic activity not only triggers the production of free oxygen radicals but also disrupts the antioxidant defense mechanism. In this case, increasing free oxygen radicals react with lipids, proteins, and carbohydrates in the cell membrane and disrupt their structure and activities. In this case, disruptions occur in reactions such as substance transport, enzymatic activity, and cell communication in the cell. Thus, hyperthyroidism causes oxidative stress-mediated cell damage.