title: Protective effects of L-dopa and carbidopa combined treatments on human catecholaminergic cells.
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 H(2)O(2), carbidopa is effective in reducing the damage caused by reactive oxygen intermediates both alone and in combination with L-Dopa.
authors.affiliation: Department of Biology, University, Roma TRE, Roma, Italy .
authors.forename: Monica
authors.initials: M
authors.lastname: Colamartino
authors.forename: Luca
authors.initials: L
authors.lastname: Padua
authors.forename: Carlo
authors.initials: C
authors.lastname: Meneghini
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cornetta
authors.forename: Antonella
authors.initials: A
authors.lastname: Testa
authors.forename: Renata
authors.initials: R
authors.lastname: Cozzi
mesh_terms: D000978:Antiparkinson Agents / Q000378:metabolism / Q000494:pharmacology; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002230:Carbidopa / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism / Q000494:pharmacology*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000978:Antiparkinson Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D016877:Oxidants; D017382:Reactive Oxygen Species; D007980:Levodopa; D006861:Hydrogen Peroxide; D004296:Dopa Decarboxylase; D002230:Carbidopa; D004298:Dopamine