Protective effects of L-dopa and carbidopa combined treatments on human catecholaminergic cells

Monica Colamartino, Luca Padua, Carlo Meneghini, Stefano Leone, Tommaso Cornetta, Antonella Testa, Renata Cozzi

Research output: Contribution to journalArticle

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative disorders characterized by decreased levels of the neurotransmitter dopamine (DA) in the striatum of the brain, as a result of degeneration of DA neurons. Levodopa (L-Dopa) crosses the blood-brain barrier and its administration replenishes the loss of DA in dopaminergic neurons in PD patients. Despite the evident beneficial effects, L-Dopa use may cause side effects and its toxicity found in in vitro assays has been attributed to the generation of reactive oxygen species (ROS): L-Dopa is converted to DA and its metabolism and autoxidation gives rise to quinones, semiquinones, and hydrogen peroxide. Despite this evidence, L-Dopa in some in vivo and in vitro experiments showed no toxic effects, or even antioxidant effects. Two major peripheral L-Dopa metabolic pathways, driven by the enzymes Aromatic L-amino acid decarboxylase (AADC) and catechol-O-methyl transferase (COMT), significantly deplete the amount of L-Dopa reaching the brain. The low bioavailability of L-Dopa may cause a wide variation in clinical response between patients. Strategies addressing to improve the bioavailability of L-Dopa include coadministering L-Dopa with carbidopa, a decarboxylase inhibitor, as multiple daily doses. We utilized catecholaminergic human neuroblastoma cells to study DNA damage and ROS production after L-Dopa and carbidopa treatments. Our data lead us to confirm that L-Dopa may have a protective effect on dopaminergic cells especially at certain concentrations, in particular, toward the production of ROS and their toxic effects on DNA. Furthermore in the combined treatment, with induction of ROS following administration of H2O2, carbidopa is effective in reducing the damage caused by reactive oxygen intermediates both alone and in combination with L-Dopa.

Original languageEnglish
Pages (from-to)1572-1579
Number of pages8
JournalDNA and Cell Biology
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 1 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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