Abstract
Background: the imbalance between reactive oxygen species (ROS) and antioxidant barrier is a typical condition of Parkinson's disease (PD), and may be the cause of oxidative alterations on DNA.
The oxidations on nucleobase guanine have been previously widely studied and the measurements of the hydroxylated form 8-hydroxy-guanine (8-OHGua) and its nucleoside 8-hydroxy-2-deoxy-guanosine (8-OHdG) have been proposed as sensible and reliable markers of this imbalance.
Objective: the study was carried out to demonstrate the relations between 8-OHGua, 8-OHdG and the corresponding non-oxidized nucleoside 2-deoxy-guanosine (2-dG) with PD clinical progression.
Method: the measurements of 8-OHGua, 8-OHdG and 2-dG were performed in urine samples of 198 PD subjects, ranked according to the Hoehn-Yahr scale (H-Y). The same analysis were also performed in a group of 33 subjects with other parkinsonisms.
Results: all markers were analyzed using high performance liquid chromatography and electrochemical detection (HPLC-ED). For 8-OHGua, a new method was specifically optimized; the low limit of detection (LOD 10 ng/L) and good intra- and inter-assay coefficients of variation (CV 2.2% and 3.6%, respectively), allowed reliable measurements of 8-OHGua in a wide range of concentrations (from 0.5 to 2000 ìg/L).
Compared to the initial stages (H-Y<2), 8-OHdG doubles in advanced ones (H-Y>2) and 2-dG halves, both with statistical significance (p <0.001).
The values of 8-OHGua also increased with the aggravation of the pathology, but in a less marked way and without statistical significance. Furthermore, the oxidative damage on guanine was more evident in males than in females, and higher in parkinsonism than in PD.
Conclusions: the redox imbalance in PD causes oxidative damage to DNA that increases with the progression of the disease. By attributing to 8-OHdG the role of marker of extent of oxidative damage, to 8-OHGua the one of efficiency of removal of oxidized bases from DNA, and to 2-dG the one of recovery of native nucleosides for the replacement of oxidized ones, our data seem to show that the DNA repair mechanisms in PD are insufficient to counteract the chronic oxidative insult that characterizes the disease.

Key words: oxidative stress markers, 8-OHdG, 8-OHGua, 2-dG, Hoehn-Yahr stage, Parkinson's disease