**5. Influence of L-dopa treatment duration on the level of oxidative damage to DNA and thiols compounds concentration in patients with Parkinson's disease**

The discussion about value of the L-dopa treatment in PD concerning on: toxicity, biochemical effects, clinical motor complications, especially after long-term its administrations (Belcastro et al., 2010; Muller, 2009a). Long-term treatment with L-dopa in PD patients may be promotes Hcy levels increase. Moreover, only PD patients with hyper-Hcy (Hcy above 15 µM) may have disturbed metabolism Hcy to Cys. As showed, hyper-Hcy in PD patients has been correlated with duration of disease and L-dopa dose.

#### **5.1 Patients (see point 2.1.1) 5.2 Analysis of Hcy and Met (see point 3.3.2), and Cys (see point 3.2.2) concentrations, and 8-oxo2dG level (see point 2.1.2) 5.3 Results**

During the initial five years and within the following 10 years of treatment with L-dopa (Table 11), the levels of 8-oxo2dG were augmented (p<0.05, as compared to the controls). Similarly to 8-oxo2dG, the levels of Hcy were highest after the initial five years of L-dopa administration (p<0.05, as compared to the controls). Subsequent treatment for another five to ten years resulted in the elevated levels of Hcy (p<0.01, as compared to the controls) which were even more significant if the treatment was extended over ten years (p<0.001, as compared to the controls). Moreover, the initial five years of L-dopa treatment were accompanied by relatively low levels of Met (p<0.05, as compared to the controls) and a slight increase in concentration of Cys. After ten years of treatment, similar levels of Hcy and Met were detected (Met, p<0.01), as compared to the controls, and Cys, (p<0.05), as compared to the group treated for five to ten years.


Table 11. Levels of oxidative DNA damage (8-oxo2dG/dG x 10-5), and homocysteine (µM), methionine (µM) and cysteine (µM) concentrations as related to duration of L-dopa administration to patients with PD. Results are expressed as means ± SD. Differences significant at \*p<0.05, \*\*p<0.01, \*\*\*p<0.001, as compared to the controls. Differences significant at (\*)p<0.05 between patients treated with L-dopa for 5-10 year and those treated for over 10 year.

As shown by the literature (Spencer et al., 1995) and by our studies, the elevated level of oxidized guanine in DNA (8-oxo2dG) in PD reflects also pharmacotherapy with L-dopa preparations. In present study, levels of 8-oxo2dG in the patients treated with L-dopa

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preparations have reflected duration of administration of the drug. Patients have seemed most exposed to oxidative stress, resulting from L-dopa administration, during the first 5 years of treatment with the preparation and following long-term (over 10 years) its administration. According to Spencer et al. (1995), the augmented oxidative stress in patients treated with L-dopa might have resulted from lowered levels of antioxidants (GSH), disturbed mitochondrial transport and from excessive oxidation of dopamine.

Reports of the literature (Miller et al., 2003) and present results indicate that plasma Hcy levels in PD have been affected also by pharmacotherapy with L-dopa. In present study levels of the sulfuric amino acid were also affected by duration of the pharmacotherapy. The most exposed to neurotoxic effects of Hcy have seemed to be the patients during the first 5 years L-dopa treatment while its continued administration has resulted in stably elevated Hcy level, it seems that all time are disturbed metabolism of Hcy to Met and Cys.

Treatment with L-dopa preparations seems to be a potential risk factor for vascular diseases in PD patients. According to Lamberti et al. (2005), administration of vitamin B12 and of folates decreases plasma level of Hcy particularly in patients with PD during treatment with L-dopa preparations and in this way prevents against intensification of vascular lesions and dementia in the patients.
