8-hydroxy-2--deoxyguanosine and Scleroderma--Systemic

Oxidative stress has been implicated in the pathogenesis of systemic sclerosis (SSc). Our objective was to determine whether SSc is associated with altered redox homeostasis in human saliva.. Study participants were 70 women with SSc and 120 female controls. 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin F 2alpha (8-epi-PGF2alpha), and total protein carbonyls were assayed by ELISA to quantify oxidative damage to nucleic acids, lipids, and proteins, respectively, in whole nonstimulated saliva.. We observed a significantly positive association between salivary log protein carbonyls and SSc in a crude statistic (OR 9.06, p < 0.0001), and multivariable model adjusted for log 8-OHdG, log 8-epi-PGF2alpha, and antioxidant exposure (OR 9.26, p < 0.0001). No significant association was noted between SSc and salivary log 8-epi-PGF2alpha or log 8-OHdG.. Salivary redox homeostasis is perturbed in patients with SSc and may inform on the pathophysiology and presence of the disease (biomarkers) and efficacy of therapeutic interventions.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Deoxyguanosine; Dinoprost; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Homeostasis; Humans; Middle Aged; Oxidation-Reduction; Oxidative Stress; Protein Carbonylation; Saliva; Scleroderma, Systemic

Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of SSc. Protein and lipid damage have previously been demonstrated, but scarce data are available on oxidative damage to DNA. In patients with SSc, we evaluated levels of 8-hydroxy-2'-deoxyguanosine (8-oxodG), the main validated biomarker of endogenous oxidative damage to DNA, compared to levels of F2-isoprostane, a product of free radical-mediated peroxidation of arachidonic acid.. Urinary levels of 8-oxodG and 8-isoprostaglandin-F(2α) (8-iso-PGF(2α)) were determined by competitive ELISA method in consecutive SSc patients and controls matched for age and sex.. We included 80 unrelated SSc patients (72 women, mean age 56 ± 11 yrs) and 39 controls (33 women, mean age 64 ± 8 yrs). Urinary levels of 8-oxodG/creat and 8-iso-PGF(2α)/creat in SSc patients were found to be higher than in controls (6.5 ng/mg vs 3.7 ng/mg, p = 0.0001; and 11.4 ng/mg vs 4.2 ng/mg, p < 0.0001). In multivariate analysis, 8-oxodG levels were associated with the presence of pulmonary fibrosis on computerized tomography scan, decreased forced vital capacity, and decreased DLCO/alveolar volume. In patients with the diffuse cutaneous subset, a modified Rodnan skin score > 14 was independently associated with 8-oxodG levels. In SSc, 8-oxodG and 8-iso-PGF(2α) values were correlated (r = 0.32; p = 0.005).. Our study confirmed marked oxidative stress in SSc. We also found increased values of 8-oxodG in SSc patients and a relevant association with a fibrotic phenotype. The predictive value of this marker and its potential influence on fibrotic disturbances remain to be determined.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Deoxyguanosine; Dinoprost; DNA Damage; Female; Humans; Lipid Peroxidation; Middle Aged; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Scleroderma, Systemic