Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves’ disease during therapy

Komosińska-Vassev, Katarzyna; Olczyk, Krystyna; Kucharz, Eugene J.; Marcisz, C; Winsz-Szczotka, Katarzyna; Kotulska, Anna

doi:10.1016/s0009-8981(00)00306-5

Cited by 123 publications

(107 citation statements)

References 33 publications

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“…Following treatment, the levels of oxidative stress and DNA damage parameters approached those of healthy controls, but were still significantly higher. This is in contrast to studies by Adali et al, [24] and Komosinska-Vassev et al, [26]. There was no significant difference between post treatment and control levels in terms of GSH in the study by Adali et al, nor in terms of GPx in the study by Komosinska-Vassev et al, Nevertheless in our study, thyroid function test results did not significantly differ between controls and patients following treatment.…”

Section: Discussioncontrasting

confidence: 99%

“…In response to oxidative stress, its activity increases, and following treatment, the overproduction of free radicals by thyroid hormones is reduced, which in turn lowers its activity, as our results indicate. Some studies support our results [26,27] while others indicate decreased levels before medical treatment [28,29]. This decrease, however, has been attributed to nutritional state of the patients [22,29].…”

Section: Discussionsupporting

confidence: 83%

“…While there have been some which report decreased activity [29], most studies demonstrate increased levels [26,30,31]. Our results support neither view, as we could not find any significant change in plasma SOD levels in patients compared to controls.…”

Section: Discussionsupporting

confidence: 47%

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Evaluation of Leukocyte DNA Damage and Antioxidant Defense in Graves’ Disease; Effect of Medical Treatment

Akçay¹,

Erdem²,

S³

2017

IJCPT

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IntroductionGraves' disease is the most common cause of hyperthyroidism [1]. It is characterized by palpitations, fatigue, heat intolerance, weight loss, and sometimes dermopathy and ophthalmopathy manifests through the progression of the disease [2]. Thyroid hormones increase oxidative metabolism by affecting basal metabolic rate and several mitochondrial enzymes [3,4], and hyperthyroidism causes changes in the antioxidant systems in various tissues by increasing the production of free radicals [5]. These radicals induce a variety of lesions in DNA, including DNA strand breaks, oxidized bases, and formation of cross-links between DNA and proteins [6]. DNA damage is constantly fixed by repair mechanisms in aerobic organisms; however, if cell division occurs before repairs are completed, the DNA damage becomes permanent [7]. A major site of radical attack is at the 8th position of guanine to yield 8-hydroxy-2-deoxyguanosine (8-OHdG). This modification might cause severe mutations [8], and sites within DNA which contain these alterations are more susceptible to strand breaks. These lesions can be detected by employing single cell gel electrophoresis, also known as comet assay. Furthermore, utilizing formamidopyrimidine DNA glycosylase (FPG), a damage specificrepair endonuclease, during this assay will cause additional strand breaks at sites with oxidized bases [9].Several antioxidant defense mechanisms exist in order to counter the harmful effects of free radicals. One of these defense agents is glutathione [10]. Glutathione, in its reduced form (GSH), is a physiological component of the intracellular antioxidant mechanisms. It acts against the effects of free radicals through serving as a cofactor for the enzyme glutathione peroxidase (GPx) [11]. Beside GPx, superoxide dismutase (SOD) is another enzyme deAbstract Background: Oxidative stress has been implicated in many pathological conditions, including hyperthyroidism. In this study, our aim was to investigate the effect of medical treatment on oxidative/antioxidative status and subsequent DNA damage in Graves' disease, in terms of reduced glutathione (GSH) levels, superoxide dismutase (SOD), glutathione peroxidase (GPx) activity and DNA strand breaks. Methods: Fifty female patients suffering from Graves' disease and thirty-seven healthy female controls were recruited in the study. Blood samples were taken from the patients before and after treatment. Free T3, free T4 and thyroid stimulating hormone (TSH) levels were determined using chemiluminescent particle assay, GSH, SOD and GPx activity using photometric techniques, and comet assay was utilized to analyze strand breaks with formamidopyrimidine DNA glycosylase (FPG) sensitive sites. Results: Free T3, free T4, GPx activity, DNA strand breaks and FPG sensitive sites were significantly higher, and TSH and GSH levels were significantly lower in patients prior to treatment compared to healthy controls. Following treatment, the levels of free T3, free T4 and TSH were restored to those of healthy controls, but the ...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 83%

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Evaluation of Leukocyte DNA Damage and Antioxidant Defense in Graves’ Disease; Effect of Medical Treatment

Akçay¹,

Erdem²,

S³

2017

IJCPT

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“…2A), the resident macrophages of the liver (29,39). In man, hyperthyroidism is characterized by significant changes in circulating parameters related to oxidative stress, including (i) higher levels of lipid peroxidation indicators (40)(41)(42)(43)(44)(45)(46)(47)(48)(49); (ii) enhancement in hydrogen peroxide and lipid hydroperoxide levels (49); and (iii) diminished levels of antioxidants such as a-tocopherol (41), coenzyme Q (44), ascorbic acid (41), and reduced thiols (42,46,50). These changes correlated with the enhancement in urinary lipid peroxidation products (40) and chemiluminescence response (51) and are either significantly reduced or normalized by thyrostatic therapy or antioxidant supplementation (40-46, 49, 50).…”

Section: T 3 -Induced Enhancement Of Liver O 2 Consumption and Oxidatmentioning

confidence: 99%

Hormetic responses of thyroid hormone calorigenesis in the liver: Association with oxidative stress

Videla

2010

IUBMB Life

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SummaryThyroid hormone (L-3,3 0 ,5-triiodothyronine, T 3 ) exerts calorigenic effects by accelerating mitochondrial O 2 consumption through transcriptional activation of respiratory genes, with consequent increased reactive oxygen species (ROS) production. In the liver, ROS generation occurs at different sites of hepatocytes and in the respiratory burst of Kupffer cells, triggering the activation of the transcription factors nuclear factor-jB, signal transducer and activator of transcription 3, and activating protein 1. Under these conditions, the redox upregulation of Kupffer cell-dependent expression of cytokines [tumor necrosis factor-a, interleukin (IL)-1, and IL-6] is achieved, which upon interaction with specific receptors in hepatocytes trigger the expression of antioxidant enzymes (manganese superoxide dismutase, inducible nitric oxide synthase), antiapoptotic proteins (Bcl-2), and acute-phase proteins (haptoglobin, b-fibrinogen). These responses and the promotion of hepatocyte and Kupffer cell proliferation observed represent hormetic effects re-establishing redox homeostasis, promoting cell survival, and protecting the liver against ischemia-reperfusion (IR) injury. It is proposed that hormesis underlying T 3 action may constitute a novel preconditioning strategy for IR injury during liver surgery in man or in liver transplantation using reduced-size grafts from living donors, considering that (i) with the exception of the controversial ischemic preconditioning, all other studied strategies have failed to reach the clinical setting and (ii) T 3 is a well-tolerated therapeutic agent that either lacks major adverse effects or has minimal and controlled side effects. IUBMBIUBMB Life, 62(6): [460][461][462][463][464][465][466] 2010

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“…Stimulation of energy metabolism by thyroid hormones implies an enhanced generation of ROS in target tissues, which determines a greater consumption of cellular antioxidants and inactivation of enzymatic mechanisms providing antioxidant protection, thus inducing oxidative stress (6). In fact, in patients with hyperthyroidism and with untreated GD, a significant increase in circulating lipid peroxidation activity indices has been described (34), which are suppressed by propylthiouracil treatment (35). In addition, T 3 administration induces an increase in ROS generation by mononuclear cells (36).…”

confidence: 99%

Decreased number of circulating endothelial progenitor cells in patients with Graves’ hyperthyroidism

Ciuceis

Pilu

Cappelli

et al. 2010

J Endocrinol Invest

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ABSTRACT. Objective: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves' hyperthyroidism (GD), in whom an increased oxidative stress was observed. Design and methods: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin ( INTRODUCTIONGraves' disease (GD) is a thyroid disorder caused by an antibody-mediated immune reaction against the receptor for TSH resulting in an abnormal chronic stimulation of the gland and consequent hyperthyroidism (1, 2). This, in turn, causes the clinical symptoms of hyperthyroidism. Indeed, thyroid hormones may exert multiple effects on the heart and vascular system, inducing an hyperkinetic status and the onset of isolated systolic hypertension (3, 4). Activation of the sympathetic and of the renin-angiotensin-aldosterone (RAS) systems may elicit a major role in inducing cardiovascular changes in GD (5). Moreover, in hyperthyroidism, an unbalance between oxidant and antioxidant substances has been identified, thus leading to enhanced generation of reactive oxygen species (ROS), able to induce vascular dysfunction and damage (6). This may be the consequence of both an activation of RAS system and of a stimulation of energy metabolism induced by thyroid hormones (5). In addition, chronic inflammation has been shown in active GD, as well as in autoimmune thyroid disorders, and production of acute-phase proteins and proinflammatory cytokines [such as interleukin (IL)-12, IL-18, and tumor necrosis factor-α (TNF-α)] (7). Hemodynamic and metabolic changes may lead to vascular injury, as suggested by an increase of markers of endothelial damage observed in GD (8-10). In the last years, endothelial progenitor cells (EPC) have been recognized to play important roles in post-natal neovascularization and vascular repair, and, therefore in maintaining endothelial integrity and function (11,12). EPC are generated from bone marrow and represent precursors which preserve stem cell features, able therefore to proliferate, migrate, and differentiate in mature endothelial cells (11,12). EPC number has been demonstrated to be correlated with the number of cardiovascular risk factors, with indices of endothelial dysfunction (13-15), and the incidence of cardiovascular events (16,17). However, no data are presently available about the EPC number in hyperthyroidism caused by GD. Therefore the aim of the present study is to investigate the presence of oxidative stress and inflammation ...

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Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves’ disease during therapy

Cited by 123 publications

References 33 publications

Evaluation of Leukocyte DNA Damage and Antioxidant Defense in Graves’ Disease; Effect of Medical Treatment

Evaluation of Leukocyte DNA Damage and Antioxidant Defense in Graves’ Disease; Effect of Medical Treatment

Hormetic responses of thyroid hormone calorigenesis in the liver: Association with oxidative stress

Decreased number of circulating endothelial progenitor cells in patients with Graves’ hyperthyroidism

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