8-hydroxy-2--deoxyguanosine and Multiple-System-Atrophy

8-hydroxy-2'-deoxyguanosine (8-OHdG) or 8-hydroxyguanosine (8-OHG), a product of oxidized DNA or RNA, is a good marker of oxidative cellular damage. In this study, we measured the 8-OHdG/8-OHG levels in the serum and cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) and multiple system atrophy (MSA). Compared to age-matched controls, the mean levels of serum 8-OHdG/8-OHG were significantly higher in PD (P < 0.0001). Although no gender differences were observed in the controls, the mean values of serum 8-OHdG/8-OHG were significantly higher in female PD cases (P < 0.005) than in male patients. 8-OHdG/8-OHG levels in CSF were also increased significantly in patients with PD and MSA, however, their relative values were generally much lower than those in the serum. Together with previous studies showing increased peripheral 8-OHdG levels in Alzheimer's disease and amyotrophic lateral sclerosis, the data presented here suggest that systemic DNA/RNA oxidation is commonly observed in neurodegenerative diseases. Our results also imply that female patients with PD show higher levels of oxidative stress, which may explain the faster progression of this disease in females.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Deoxyguanosine; DNA; Enzyme-Linked Immunosorbent Assay; Female; Guanosine; Humans; Male; Middle Aged; Multiple System Atrophy; Oxidation-Reduction; Oxidative Stress; Parkinson Disease; RNA

There is growing evidence for the involvement of oxidative stress and mitochondrial respiratory failure in nigral neuronal death in Parkinson's disease (PD). We report increased immunoreactivity of 8-oxo-dGTPase (8-oxo-7, 8-dihydrodeoxyguanosine triphosphatase [hMTH1]), an enzyme known to play an important role in controlling spontaneous mutagenesis, and 8-oxo-7, 8-deoxyguanosine (8-oxo-dG) in the mitochondria of the substantia nigra of 6 PD patients. Our results suggest that hMTH1 might be a useful marker of oxidative stress and can be used to explore the relation between such oxidative stress and genomic instability.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Deoxyguanosine; DNA Repair Enzymes; Humans; Immunohistochemistry; Mitochondria; Models, Chemical; Multiple System Atrophy; Neurons; Oxidative Stress; Parkinson Disease; Phosphoric Monoester Hydrolases; Reference Values; Substantia Nigra