Oxidative Stress Change by Systemic Corticosteroid Treatment Among Patients Having Active Graves Ophthalmopathy

Abstract

To measure the 8-hydroxy-2Ј-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. Methods: 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. Results: 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 Ͻ .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levels were subsequently elevated in 2 patients having recurrent active GO when corticosteroid therapy was tapered or withdrawn. Conclusions: 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.

Oxidative stress in patients with Graves' ophthalmopathy: relationship between oxidative DNA damage and clinical evolution

“…Moreover, one of our earlier studies demonstrated that patients with active GO on maximal systemic steroid and after treatment had significantly lower urinary level of 8-OHdG (7.19 and 10.18 ng/mg creatinine, respectively) as compared with those before Table 3 The mean urinary 8-OHdG levels (ng/mg creatinine) of never smoker and current/ex-smoker among both groups treatment (17.47 ng/mg creatinine), and these changes were accompanied by a decrease of CAS and OI. 20 In addition, our current findings showed that the urinary 8-OHdG level was closely associated with the CAS of the GO patients. It appears that oxidative DNA damage may be a pathogenic factor, particularly in the inflammatory process of GO.…”

“…In an earlier study, we disclosed that there was a higher urinary 8-hydroxy-2 0 -deoxyguanosine (8-OHdG) level in eight patients with active GO, and this biomarker of oxidative DNA damage could be reduced after treatment with steroid. 20 This study was further carried out to investigate the urinary 8-OHdG level in GO patients and evaluated the association between urinary level of 8-OHdG and clinical evolution of GO, to realize more about the role of oxidative stress in the pathophysiology of GO, and hope to open up a potential new avenues for developing novel treatments for GO.…”

Increased oxidative DNA damage, lipid peroxidation, and reactive oxygen species in cultured orbital fibroblasts from patients with Graves’ ophthalmopathy: evidence that oxidative stress has a role in this disorder

“…We have previously reported that systemic corticosteroids are effective in reduction of both the clinical manifestation and oxidative DNA damage in patients with active GO. 21 In a small case series, oral antioxidants provided beneficial effect in the treatment of mild and moderately severe GO. 40 However, more basic work and clinical studies are warranted to provide more information about the role of antioxidants and corticosteroids in the treatment of GO, especially those patients with coexisting oxidative stress.…”

“…20 Furthermore, this biomarker of oxidative DNA damage could be reduced after treatment with systemic steroid in patients with active GO. 21 In this investigation, we determined the oxidative DNA damage in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with GO and compared them with the controls. In addition, lipid peroxidation and intracellular ROS levels in cultured orbital fibroblasts were also determined.…”

Oxidative Stress in Graves’ Disease

“…Interestingly, in the study by Bednarek et al [21], which also included Graves’ patients with active GO, increased peripheral ROS and antioxidant activity normalized only in patients without GO, suggesting that orbital inflammation contributed to the increased circulating markers of the oxidative status. Tsai et al [41] showed increased oxidative DNA damage, as evaluated by measurement of urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels, compared with controls, in 8 patients with active GO who had been rendered euthyroid for at least 6 months with ATD therapy. Treatment with oral glucocorticoids (GC) was associated with a significant decrease of urinary 8-OHdG compared with pretreatment levels, which paralleled changes in the clinical activity score and ophthalmopathy index.…”