Evaluation of Levodopa and Carbidopa Antioxidant Activity in Normal Human Lymphocytes In Vitro: Implication for Oxidative Stress in Parkinson’s Disease

Monica Colamartino, Massimo Santoro, Guglielmo Duranti, Stefania Sabatini, Roberta Ceci, Antonella Testa, Luca Padua, Renata Cozzi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)106-117
Number of pages12
JournalNeurotoxicity Research
Volume27
Issue number2
DOIs
Publication statusPublished - 2014

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Keywords

  • Carbidopa
  • l-Dopa
  • Oxidative stress
  • Parkinson’s disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology
  • Medicine(all)

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