title: Evaluation of levodopa and carbidopa antioxidant activity in normal human lymphocytes in vitro: implication for oxidative stress in Parkinson's disease.
abstract: The main pathochemical hallmark of Parkinson's disease (PD) is the loss of dopamine in the striatum of the brain, and the oral administration of levodopa (L-dopa) is a treatment that partially restores the dopaminergic transmission. In vitro assays have demonstrated both toxic and protective effects of L-dopa on dopaminergic cells, while in vivo studies have not provided any convincing data. The peripheral metabolic pathways significantly decrease the amount of L-dopa reaching the brain; therefore, all of the current commercial formulations require an association with an inhibitor of dopa-decarboxylase, such as carbidopa. However, the dosage and the actual effectiveness of carbidopa have not yet been well defined. PD patients exhibit a reduced efficiency of the endogenous antioxidant system, and peripheral blood lymphocytes (PBLs) represent a dopaminergic system for use as a cellular model to study the pharmacological treatments of neurodegenerative disorders in addition to analysing the systemic oxidative stress. According to our previous studies demonstrating a protective effect of both L-dopa and carbidopa on neuroblastoma cells in vitro, we used the PBLs of healthy donors to evaluate the modulation of DNA damage by different concentrations of L-dopa and carbidopa in the presence of oxidative stress that was exogenously induced by H2O2. We utilised a TAS assay to evaluate the in vitro direct scavenging activity of L-dopa and carbidopa and analysed the expression of genes that were involved in cellular oxidative metabolism. Our data demonstrate the antioxidant capacity of L-dopa and carbidopa and their ability to protect DNA against oxidative-induced damage that derives from different mechanisms of action.
authors.affiliation: Department of Science, University "Roma Tre", Viale Guglielmo Marconi 446, 00146, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Colamartino
authors.forename: Massimo
authors.initials: M
authors.lastname: Santoro
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Duranti
authors.forename: Stefania
authors.initials: S
authors.lastname: Sabatini
authors.forename: Roberta
authors.initials: R
authors.lastname: Ceci
authors.forename: Antonella
authors.initials: A
authors.lastname: Testa
authors.forename: Luca
authors.initials: L
authors.lastname: Padua
authors.forename: Renata
authors.initials: R
authors.lastname: Cozzi
mesh_terms: D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity; D002230:Carbidopa / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology* / Q000633:toxicity; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D007980:Levodopa; D002230:Carbidopa