Oxidative damage on nucleobases and Hoehn-Yahr stage in Parkinsons disease

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 ig/L). Compared to the initial stages (H-Y2) and 2-dG halves, both with statistical significance (p