High DNA oxidative damage in systemic sclerosis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Avouac
Jerome
J
Service de Rhumatologie A, Hôpital Cochin, Université Paris Descartes, AP-HP, Paris, France.
Borderie
Didier
D
Ekindjian
Ovanesse Garabed
OG
Kahan
Andre
A
Allanore
Yannick
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000652:urine
D017382:Reactive Oxygen Species; C075750:8-epi-prostaglandin F2alpha; D000080242:8-Hydroxy-2'-Deoxyguanosine; D015237:Dinoprost; D003849:Deoxyguanosine