Levodopa therapy reduces DNA damage in peripheral blood cells of patients with Parkinson’s disease

Abstract

Oxidative stress seems to play a major role in the pathogenesis of neurodegeneration. In Parkinson's disease (PD) patients, the dopaminergic neurons are subjected to oxidative stress resulting from reduced levels of antioxidant defenses such as glutathione and high amount of intracellular iron. Levodopa (LD) is widely used for the symptomatic treatment of PD, but its role in oxidative damage control is still unclear. The aim of this study was to analyze the presence of DNA damage in peripheral blood lymphocytes (PBL) of PD patients, during a washout and a controlled LD dosage and to evaluate the oxidative damage fluctuation after LD intake. The standard and the Fpg-modified version of Comet assay were applied in analyzing DNA damage in PBL from blood samples of nine PD patients and nine matched controls. Due to the limited number of patients we cannot reach definite conclusions even if our data confirm the accumulation of DNA lesions in PD patients; these lesions decrease after LD intake.

The Role of Innate and Adaptive Immunity in Parkinson's Disease

“…Lymphocytes from PD patients display an increased incidence of micronuclei, single strand DNA breaks, and oxidized purine bases [109]. Interestingly, levodopa treatment seems to reduce this DNA damage in peripheral blood lymphocytes [110]. Markers of apoptosis, caspase-3, and Cu/Zn superoxide dismutase activity are increased in lymphocytes from people with PD [111].…”

Recent advances in pharmacological therapy of Parkinson’s disease: Levodopa and carbidopa protective effects against DNA oxidative damage

“…Apart from baseline damage present in PD patients, L-Dopa does not seem to have an adverse effect, but rather a protective effect both on lymphocytes [72] and on human dopaminergic cell line [76].…”

“…These results were still left open the debate on L-Dopa until 2009, when our research group [72] analyzed the presence of DNA damage in peripheral blood lymphocytes [6] isolated from blood samples of nine PD patients and nine matched controls, during a controlled dosage and washout of L-Dopa. We evaluated the oxidative DNA damage fluctuation after L-Dopa intake through the standard and the Fpg-modified version of Comet assay.…”

Homocysteine Level and Mechanisms of Injury in Parkinson's Disease as Related to MTHFR, MTR, and MTHFD1 Genes Polymorphisms and LDopa Treatment

“…Some studies (e.g. [68]) suggest a toxic effect of L-dopa on neuronal cell in vitro, while in vivo studies in animal models are contradictory. Since less than 5% of an oral dose of L-dopa is delivered to the brain, the remaining plasma levels of the drug undergo peripheral oxidative metabolism and may generate ROS.…”

“…Since less than 5% of an oral dose of L-dopa is delivered to the brain, the remaining plasma levels of the drug undergo peripheral oxidative metabolism and may generate ROS. It is likely that the peripheral oxidation status in PD might be affected by L-dopa therapy [68]. The study of Spencer et al [69] showed that the augmented oxidative stress in PD patients treated with L-dopa might influence the degree of reduction of antioxidants (GSH), disturbed mitochondrial transport, and excessive oxidation of dopamine.…”