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## Meet the editors

Dr. Volkan Gelen is a physiology specialist who received his veterinary degree from Kafkas University, Turkey, in 2011. From 2011 to 2015, he worked as an assistant in the Department of Physiology, Faculty of Veterinary Medicine, Atatürk University, Turkey. In 2016, he joined Kafkas University as an assistant professor where he has been engaged in various academic activities. Dr. Gelen has sixty journal articles and twenty poster presenta-

tions to his credit. His research interests include physiology, the endocrine system, cancer, diabetes, cardiovascular diseases, and isolated organ bath system studies.

Dr. Abdulsamed Kükürt graduated from Uludağ University, Turkey. In 2019, he obtained a Ph.D. in Biochemistry from the Institute of Health Sciences, Kafkas University, Turkey, where he is currently an assistant professor in the Department of Biochemistry. He has published twenty-eight research articles in academic journals, eleven book chapters, and thirty-seven papers. Dr. Kükürt has participated in ten academic projects and

is a reviewer for many academic journals.

Dr. Emin Şengül is a physiology specialist who received his veterinary degree from Atatürk University, Turkey, in 2008. In 2014, he became an assistant professor at the same university. He has published sixty-two journal articles and given twenty poster presentations at scientific congresses. His research interests include physiology, the endocrine system, cancer, diabetes, gastric ulcer, neurotoxicity, testicular toxicity, nephrotoxicity,

cardiovascular diseases, and isolated organ bath system studies.

### Contents



Preface

Hyperthyroidism involves physiological, biological, and clinical factors that cause hypermetabolism due to the excessive elevation of thyroid hormones in the blood and the surrounding tissues under the influence of high levels of hormones. There is a general acceleration in metabolism. The term 'thyrotoxicosis' is sometimes used to describe this syndrome. Symptoms include irritability, nervousness, excessive sweating, increased blood pressure and breathing, tachycardia, shortness of breath, diarrhea, goiter, exophthalmos, and skin changes. Graves' disease is a very common autoimmune disease. Antithyroid drugs, lithium carbonate, radioactive iodine, and dexamethasone are used in the treatment of hyperthyroidism. Thyrotoxicosis is characterized by hypermetabolism and hyperactivity syndrome, in which serum concentrations of T4, T3, or both are increased. Diseases that cause hyperthyroidism can originate from the thyroid gland, as well as from pituitary or non-pituitary causes. Hyperthyroidism is categorized into three groups: primary, secondary, and subclinical hyperthyroidism. This book provides comprehensive and important information on the secretion and functions of thyroid hormones, as well as the causes, types,

symptoms, associated diseases, and treatments of hyperthyroidism.

**Volkan Gelen,** 

Kafkas University, Kars, Turkey

Kafkas University, Kars, Turkey

Atatürk University, Erzurum, Turkey

**Emin Şengül,**

**Abdulsamed Kükürt,**

Faculty of Veterinary Medicine, Department of Physiology,

Faculty of Veterinary Medicine, Deparment of Biochemistry,

Faculty of Veterinary Medicine, Department of Physiology,

## Preface

Hyperthyroidism involves physiological, biological, and clinical factors that cause hypermetabolism due to the excessive elevation of thyroid hormones in the blood and the surrounding tissues under the influence of high levels of hormones. There is a general acceleration in metabolism. The term 'thyrotoxicosis' is sometimes used to describe this syndrome. Symptoms include irritability, nervousness, excessive sweating, increased blood pressure and breathing, tachycardia, shortness of breath, diarrhea, goiter, exophthalmos, and skin changes. Graves' disease is a very common autoimmune disease. Antithyroid drugs, lithium carbonate, radioactive iodine, and dexamethasone are used in the treatment of hyperthyroidism. Thyrotoxicosis is characterized by hypermetabolism and hyperactivity syndrome, in which serum concentrations of T4, T3, or both are increased. Diseases that cause hyperthyroidism can originate from the thyroid gland, as well as from pituitary or non-pituitary causes. Hyperthyroidism is categorized into three groups: primary, secondary, and subclinical hyperthyroidism. This book provides comprehensive and important information on the secretion and functions of thyroid hormones, as well as the causes, types, symptoms, associated diseases, and treatments of hyperthyroidism.

#### **Volkan Gelen,**

Faculty of Veterinary Medicine, Department of Physiology, Kafkas University, Kars, Turkey

#### **Abdulsamed Kükürt,**

Faculty of Veterinary Medicine, Deparment of Biochemistry, Kafkas University, Kars, Turkey

#### **Emin Şengül,**

Faculty of Veterinary Medicine, Department of Physiology, Atatürk University, Erzurum, Turkey

**1**

Section 1

Introduction

Section 1 Introduction

#### **Chapter 1**

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

*Volkan Gelen and Abdulsamed Kükürt*

#### **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 [4–6]. 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 [18–20]. 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.*

*Introductory Chapter: The Relationship between Hyperthyroidism and Oxidative… DOI: http://dx.doi.org/10.5772/intechopen.111572*

#### **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.

#### **Author details**

Volkan Gelen1 \* and Abdulsamed Kükürt2

1 Faculty of Veterinary Medicine, Department of Physiology, Kafkas University, Kars, Türkiye

2 Faculty of Veterinary Medicine, Department of Biochemistry, Kafkas University, Kars, Türkiye

\*Address all correspondence to: gelen\_volkan@hotmail.com

© 2023 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **References**

[1] Jakubczyk K, Dec K, Kałduńska J, Kawczuga D, Kochman J, Janda K. Reactive oxygen species—Sources, functions, oxidative damage. Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego. 2020;**48**:124-127

[2] Tan BL, Norhaizan ME, Liew W-P-P. Nutrients and oxidative stress: Friend or foe? Oxidative Medicine and Cellular Longevity. 2018;**9719584**

[3] Yang S, Lian G. ROS and diseases: Role in metabolism and energy supply. Molecular and Cellular Biochemistry. 2020;**467**:1-12

[4] Gelen V, Şengül E, Yıldırım S, Senturk E, Tekin S, Kükürt A. The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environmental Science and Pollution Research. 2021;**28**:47046-47055. DOI: 10.1007/ s11356-021-13969-5

[5] Yun HR, Jo YH, Kim J, Shin Y, Kim SS, Choi TG. Roles of autophagy in oxidative stress. International Journal of Molecular Sciences. 2020;**21**:3289

[6] Sies H. Oxidative stress: A concept in redox biology and medicine. Redox Biology. 2015;**4**:180-183

[7] Gelen V, Şengül E. Antioxidant, antiinflammatory and antiapoptotic effects of naringin on cardiac damage induced by cisplatin. Indian Journal of Traditional Knowledge. 2020;**19**:459-465

[8] Kara A, Gedikli S, Sengul E, Gelen V, Ozkanlar S. Oxidative stress and autophagy. In: Ahmad R, editor. Free Radicals and Diseases. London: IntechOpen; 2016. pp. 69-86. DOI: 10.5772/64569

[9] Sengul E, Gelen V, Yildirim S, Cinar İ, Aksu EH. Effects of naringin on oxidative stress, inflammation, some reproductive parameters, and apoptosis in acrylamide-induced testis toxicity in rat. Environmental Toxicology. 2023 Mar;**38**(4):798-808

[10] Gu Y, Han J, Jiang C, Zhang Y. Biomarkers, oxidative stress and autophagy in skin aging. Ageing Research Reviews. 2020;**59**:101036

[11] Vostrikova SM, Grinev AB, Gogvadze VG. Reactive oxygen species and antioxidants in carcinogenesis and tumor therapy. Biochemistry (Moscow). 2020;**85**:1254-1266

[12] Kükürt A, Gelen V, Başer ÖF, Deveci HA, Karapehlivan M. Thiols: Role in oxidative stress-related disorders. In: Atukeren P, editor. Accenting Lipid Peroxidation. London: IntechOpen; 2021. pp. 27-47. DOI: 10.5772/intechopen.96682

[13] Jakubczyk K, Kałduńska J, Dec K, Kawczuga D, Janda K. Antioxidant properties of small-molecule nonenzymatic compounds. Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego. 2020;**48**:128-132

[14] Kowalska K, Brodowski J, Pokorska-Niewiada K, Szczuko M. The change in the content of nutrients in diets eliminating products of animal origin in comparison to a regular diet from the area of Middle-Eastern Europe. Nutrients. 2020;**12**:2986

[15] Gelen V, Yıldırım S, Şengül E, Çınar A, Çelebi F, Küçükkalem M, et al. Naringin attenuates oxidative stress, inflammation, apoptosis, and oxidative DNA damage in acrylamide-induced nephrotoxicity in rats. Asian Pacific

*Introductory Chapter: The Relationship between Hyperthyroidism and Oxidative… DOI: http://dx.doi.org/10.5772/intechopen.111572*

Journal of Tropical Biomedicine. 2022;**12**(5):223-232

[16] Sies H, Jones DP. Reactive oxygen species (ros) as pleiotropic physiological signalling agents. Nature Reviews. Molecular Cell Biology. 2020;**21**:363-383

[17] Gelen V, Kükürt A, Şengül E, Devecı HA. Leptin and its role in oxidative stress and apoptosis: An overview. In: Role of Obesity in Human Health and Disease. [Working Title]. London, UK: IntechOpen; 2021. DOI: 10.5772/intechopen.101237

[18] Kim Y-M, Kim S-J, Tatsunami R, Yamamura H, Fukai T, Ushio-Fukai M. ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis. American Journal of Physiology. Cell Physiology. 2017;**312**:C749-C764

[19] Aldosari S, Awad M, Harrington EO, Sellke FW, Abid MR. Subcellular reactive oxygen species (ROS) in cardiovascular pathophysiology. Antioxidants Basel Switzerland. 2018;**7**:14

[20] Irazabal MV, Torres VE. Reactive oxygen species and redox signaling in chronic kidney disease. Cell. 2020;**9**:1342

[21] Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: A meta-analysis. The Journal of Clinical Endocrinology and Metabolism. 2014;**99**:923-931

[22] Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Archives of Internal Medicine. 2000;**160**:526-534

[23] Kasagi K, Takahashi N, Inoue G, Honda T, Kawachi Y, Izumi Y. Thyroid function in Japanese adults as assessed by a general health checkup system in relation with thyroid-related antibodies and other clinical parameters. Thyroid. 2009;**19**:937-944

[24] Empson M, Flood V, Ma G, Eastman CJ, Mitchell P. Prevalence of thyroid disease in an older Australian population. Internal Medicine Journal. 2007;**37**:448-455

[25] Rostami R, Aghasi MR, Mohammadi A, Nourooz-Zadeh J. Enhanced oxidative stress in Hashimoto's thyroiditis: Interrelationships to biomarkers of thyroid function. Clinical Biochemistry. 2013;**46**:308-312

[26] Ameziane El Hassani R, Buffet C, Leboulleux S, Dupuy C. Oxidative stress in thyroid carcinomas: Biological and clinical significance. Endocrine-Related Cancer. 2019;**26**:R131-R143

[27] Fahim YA, Sharaf NE, Hasani IW, Ragab EA, Abdelhakim HK. Assessment of thyroid function and oxidative stress state in foundry workers exposed to lead. Journal of Health and Pollution. 2020;**10**:200903

[28] Lassoued S, Mseddi M, Mnif F, Abid M, Guermazi F, Masmoudi H, et al. A comparative study of the oxidative profile in Graves' disease, Hashimoto's thyroiditis, and papillary thyroid cancer. Biological Trace Element Research. 2010;**138**:107-115

[29] Eleutherio ECA, Magalhães RSS, de Araújo Brasil A, Neto JRM, de Holanda Paranhos L. More than just an antioxidant. Archives of Biochemistry and Biophysics. 2021;**15**(697):108701

[30] Sepasi Tehrani H, Moosavi-Movahedi AA. Catalase and its mysteries. Progress in Biophysics and Molecular Biology. 2018;**140**:5-12

[31] Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radical Biology & Medicine. 2016;**95**:27-42

[32] Metere A, Frezzotti F, Graves CE, Vergine M, De Luca A, Pietraforte D, et al. A possible role for selenoprotein glutathione peroxidase (GPx1) and thioredoxin reductases (TrxR1) in thyroid cancer: Our experience in thyroid surgery. Cancer Cell International. 2018;**18**:7

[33] Torun AN, Kulaksizoglu S, Kulaksizoglu M, Pamuk BO, Isbilen E, Tutuncu NB. Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism. Clinical Endocrinology. 2009;**70**:469-474

[34] Erdamar H, Cimen B, Gülcemal H, Saraymen R, Yerer B, Demirci H. Increased lipid peroxidation and impaired enzymatic antioxidant defense mechanism in thyroid tissue with multinodular goiter and papillary carcinoma. Clinical Biochemistry. 2010;**43**:650-654

[35] Loomis SJ, Chen Y, Sacks DB, Christenson ES, Christenson RH, Rebholz CM, et al. Cross-sectional analysis of AGE-CML, SRAGE, and EsRAGE with diabetes and cardiometabolic risk factors in a community-based cohort. Clinical Chemistry. 2017;**63**:980-989

[36] Ruggeri RM, Giovinazzo S, Barbalace MC, Cristani M, Alibrandi A, Vicchio TM, et al. Influence of dietary habits on oxidative stress markers in Hashimoto's thyroiditis. Thyroid. 2021;**31**:96-105

[37] Kasai H. Analysis of a form of oxidative DNA damage, 8-hydroxy-20 deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis. Mutation Research/Reviews in Mutation Research. 1997;**387**:147-163

[38] Rovcanin BR, Gopcevic KR, Kekic DL, Zivaljevic VR, Diklic AD, Paunovic IR. Papillary thyroid carcinoma: A malignant tumor with increased antioxidant defense capacity. The Tohoku Journal of Experimental Medicine. 2016;**240**:101-111

[39] Ates I, Arikan MF, Altay M, Yilmaz FM, Yilmaz N, Berker D, et al. The effect of oxidative stress on the progression of Hashimoto's thyroiditis. Archives of Physiology and Biochemistry. 2018;**124**:351-356

### Section 2
