TY - JOUR
T1 - Evaluation of Levodopa and Carbidopa Antioxidant Activity in Normal Human Lymphocytes In Vitro: Implication for Oxidative Stress in Parkinson's Disease
AU - Santoro, Massimo
AU - Duranti, G
AU - Sabatini, S
AU - Ceci, R
AU - Testa, A
AU - Padua, Luca
AU - Cozzi, R.
AU - Colamartino, M
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Parkinson
KW - carbidopa antioxidant activity
KW - levodopa
KW - Parkinson
KW - carbidopa antioxidant activity
KW - levodopa
UR - https://publicatt.unicatt.it/handle/10807/63757
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84921371017&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84921371017&origin=inward
U2 - 10.1007/s12640-014-9495-7
DO - 10.1007/s12640-014-9495-7
M3 - Article
SN - 1029-8428
SP - 106
EP - 117
JO - Neurotoxicity Research
JF - Neurotoxicity Research
IS - 27
ER -