8-hydroxy-2--deoxyguanosine and Graves-Ophthalmopathy

Thyroid-associated orbitopathy (TAO) is the most common autoimmune disease of the orbit. It occurs more often in patients presenting with hyperthyroidism, characteristic of Graves' disease, but may be associated with hypothyroidism or euthyroidism. The diagnosis of TAO is based on clinical orbital features, radiological criteria, and the potential association with thyroid disease. To date, there is no specific marker of the orbital disease, making the early diagnosis difficult, especially if the orbital involvement precedes the thyroid dysfunction.. The goal of this review is to present the disease and combine the available data in the literature concerning investigation of TAO biomarkers.. Despite the progress done in the understanding of TAO disease, some important pieces are still missing. Typically, for the future, major efforts have to be done in the discovery of new biomarkers, validation of the suspected candidates on multicenter cohorts with standardized methodologies, and establishment of their clinical performances on the specific clinical application fields in order to improve not only the management of the TAO patients but also the therapeutic options and follow-up.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Autoantibodies; Biomarkers; Cytokines; Deoxyguanosine; Graves Ophthalmopathy; Humans

To investigate the concentrations of oxidative stress markers, 8-hydroxy-2'-deoxyquanosine (8-OHdG) and malondialdehyde (MDA), in tears and their correlation with the clinical activity score (CAS) in patients with Graves' orbitopathy (GO) according to disease activity.. We recruited 27 participants with inactive stage GO, 35 participants with active stage GO, and 25 healthy controls without GO. The tear concentrations of 8-OHdG and MDA were determined by enzyme-linked immunosorbent assay. The correlation between CAS and the concentrations of tear 8-OHdG and MDA were analyzed according to the disease activity in the GO patients.. The levels of 8-OHdG and MDA were 56.30 ± 16.81 ng/mL and 5.39 ± 1.31 pmol/mg, respectively, in the control subjects, and 123.46 ± 22.67 ng/mL and 13.59 ± 3.93 pmol/mg, respectively, in patients with inactive stage GO, and 215.14 ± 35.61 ng/mL and 22.52 ± 4.63 pmol/mg, in patients with active stage GO. The mean concentrations of 8-OHdG and MDA were higher in patients with inactive and active stage GO compared with the control group (all P < 0.001). Furthermore, in the active stage group, tear concentrations of 8-OHdG and MDA were higher than those in the inactive stage group (all P < 0.001). The level of 8-OHdG (r = 0.676, P < 0.001) and MDA (r = 0.506, P = 0.002) correlated with CAS in the active stage GO group.. The concentrations of 8-OHdG and MDA in tears increased in patients with GO, especially in those in the active stage. In patients with active stage GO, CAS correlated significantly with the tear 8-OHdG and MDA levels.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Case-Control Studies; Deoxyguanosine; Female; Graves Ophthalmopathy; Humans; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Severity of Illness Index; Tears; Young Adult

To investigate whether orbital fibroblasts from patients with Graves' ophthalmopathy (GO) are more responsive to oxidative stress.. Lipid peroxidation, oxidative DNA damage, reactive oxygen species (ROS) contents and activities of antioxidant enzymes were measured in cultured orbital fibroblasts from GO patients and age-matched normal controls in response to 200 μM hydrogen peroxide (H(2)O(2)).. GO fibroblasts had increased basal levels of malondialdehyde (MDA), 8-hydroxy 2'-deoxyguanosine, superoxide anions, H(2)O(2), and manganese-dependent superoxide dismutase (Mn-SOD) activity, as well as decreased glutathione peroxidase (GPx) activity and the ratio between reduced (GSH) and oxidized glutathione (GSSG) compared with the orbital fibroblasts from normal subjects. After treatment of the cells with 200 μM H(2)O(2), the amplitude of increase in the intracellular levels of MDA (63% versus 26%), H(2)O(2) (24% versus 13%) and Mn-SOD activity (48% versus 23%) was exaggerated in GO fibroblasts compared with normal controls, respectively. In addition, treatment of GO fibroblasts with 200 μM H(2)O(2) led to a dramatic reduction of catalase activity (-59% versus -29%), GPx activity (-56% versus -13%), and GSH/GSSG ratio (-49% versus -21%), respectively.. Elevated ROS and redox imbalance in GO orbital fibroblasts were exacerbated by H(2)O(2) as a result of exhaustion of GSH and compromise of antioxidant enzymes. Hypersensitivity to oxidative stress of GO orbital fibroblasts may play a role in the pathogenesis of GO.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Case-Control Studies; Catalase; Cells, Cultured; Deoxyguanosine; DNA Damage; Fibroblasts; Glutathione; Glutathione Disulfide; Glutathione Peroxidase; Glutathione Reductase; Graves Ophthalmopathy; Humans; Hydrogen Peroxide; Lipid Peroxidation; Malondialdehyde; Orbit; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Superoxide Dismutase

We investigated the oxidative stress in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with Graves' ophthalmopathy (GO).. The content of 8-hydroxy 2'-deoxyguanosine (8-OHdG), an important biomarker of oxidative DNA damage, was measured in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with GO and compared with age-matched normal controls. A product of lipid peroxidation, malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) in cultured orbital fibroblasts was also determined.. There was no significant difference in the 8-OHdG content of orbital fibroadipose tissues between patients with GO and age-matched normal controls (P=0.074). However, the levels of 8-OHdG and MDA in GO orbital fibroblasts were significantly higher than those of normal controls (P=0.0026 and P<0.001, respectively). In addition, GO orbital fibroblasts had higher contents of superoxide anions and hydrogen peroxide compared with those of normal controls (P=0.0133 and 0.0025, respectively).. Orbital fibroblasts represent the most abundant cell type among orbital connective tissues and exhibit great differences in their phenotypes. Increased oxidative DNA damage and lipid peroxidation, as well as higher intracellular ROS levels in GO orbital fibroblasts may have a role in the pathogenesis of GO.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adipose Tissue; Biomarkers; Cells, Cultured; Deoxyguanosine; DNA Damage; Fibroblasts; Graves Ophthalmopathy; Humans; Hydrogen Peroxide; Lipid Peroxidation; Malondialdehyde; Orbit; Oxidative Stress; Reactive Oxygen Species; Superoxides

To evaluate the relationship between oxidative stress and clinical evolution in patients with Graves' ophthalmopathy (GO).. Thirty-one euthyroid GO patients and 25 healthy subjects participated in this study. Oxidative DNA damage was assessed by determination of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in urine by ELISA. The relationship of oxidative DNA damage to the clinical evolutions of GO, especially the smoking status, clinical activity scores (CAS), and ophthalmopathy index was examined.. The mean 8-OHdG was significantly higher in GO patients than that of normal controls (12.6+/-5.7 vs 6.7+/-2.5 ng/mg creatinine, P<0.001). Smokers had significant higher 8-OHdG than did never smokers in GO patients (P=0.029), but not in healthy controls (P=0.374). Among GO patients, only CAS remained significantly correlated with 8-OHdG (P=0.001) after adjusting for age, sex, disease duration, the status of antithyroid drug and smoking, and thyroid-stimulating hormone level. Patients with active GO (CAS>3) had higher 8-OHdG than did the patients with CAS

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Creatinine; Deoxyguanosine; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Graves Ophthalmopathy; Humans; Male; Middle Aged; Oxidative Stress; Prospective Studies; Severity of Illness Index; Smoking; Young Adult

To measure the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients having active Graves ophthalmopathy (GO) and to compare this oxidative stress biomarker and the clinical evolution of patients after systemic corticosteroid treatment.. In 8 euthyroid patients having active GO, we determined the 8-OHdG levels in urine before, during, and after intensive corticosteroid therapy. Clinical activity and ophthalmopathy index scores were assessed. Nine age- and sex-matched healthy volunteers served as control subjects.. The mean 8-OHdG level was statistically significantly increased in patients having active GO compared with that of controls (17.47 vs 5.97 ng/mg of creatinine, P < .001). During and after maximal systemic corticosteroid treatment, patients had statistically significantly lower mean 8-OHdG levels (7.19 and 10.18 ng/mg of creatinine, respectively) compared with the mean level before treatment. These changes were accompanied by decreases in clinical activity and ophthalmopathy index scores. The urinary 8-OHdG levels were subsequently elevated in 2 patients having recurrent active GO when corticosteroid therapy was tapered or withdrawn.. Oxidative stress may have a role in the pathogenesis of GO. Urinary 8-OHdG level can be used not only as a noninvasive biomarker of oxidative stress in patients having GO but also as an objective and quantitative parameter in the follow-up of patients during immunosuppressive treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Oral; Adult; Biomarkers; Deoxyguanosine; Enzyme-Linked Immunosorbent Assay; Female; Glucocorticoids; Graves Ophthalmopathy; Humans; Male; Middle Aged; Oxidative Stress; Prednisolone