Back to Search
Start Over
Protective Effects of L-Dopa and Carbidopa Combined Treatments on Human Catecholaminergic Cells.
- Source :
-
DNA & Cell Biology . Nov2012, Vol. 31 Issue 11, p1572-1579. 8p. 6 Graphs. - Publication Year :
- 2012
-
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. In Parkinson's disease, the neurotransmitter dopamine is produced at decreased levels in the brain region substantia nigra. In this study, two pathways used for peripheral metabolism of L-Dopa were examined and a beneficial influence of carbidopa on reactive oxygen species and their toxic impact on host DNA were found. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10445498
- Volume :
- 31
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- DNA & Cell Biology
- Publication Type :
- Academic Journal
- Accession number :
- 82762755
- Full Text :
- https://doi.org/10.1089/dna.2011.1546