Abstract
ObjectiveThis study aimed to investigate the influence of low-dose levodopa (L-DOPA) on neuronal cell death under oxidative stress.MethodsPC12 cells were treated with L-DOPA at different concentrations. We detected the L-DOPA induced reactive oxygen species (ROS). Meanwhile, MTT and LDH assay were performed to determine the proliferation and growth of PC12 cells with or without ROS scavenger. In addition, after pretreatment with L-DOPA at different concentrations alone or in combination with CD39 inhibitor, PC12 cells were incubated with hydrogen peroxide (H2O2) and the cell viability was evaluated by MTT and LDH assay. In addition, the expression of pCREB and CD39 was detected by immunofluorescence staining and Western blot assay in both cells and rat’s brain after L-DOPA treatment.ResultsAfter treatment with L-DOPA for 3 days, the cell proliferation and growth were promoted when the L-DOPA concentration was <30 µM, while cell proliferation was comparable to that in control group when the L-DOPA concentration was >30 µM. Low dose L-DOPA could protect the PC12 cells from H2O2 induced oxidative stress, which was compromised by CD39 inhibitor. In addition, the expression of CD39 and pCREB increased in both PC12 cells and rats’ brain after L-DOPA treatment.ConclusionsL-DOPA at different concentrations has distinct influence on proliferation and growth of PC12 cells, and low dose (<30 µM) L-DOPA protects PC12 cells against oxidative stress which might be related to the up-regulation of CD39 and pCREB expression.
Highlights
Levodopa (L-DOPA) is the most widely used drug in the treatment of Parkinson’s disease (PD)
Elevated oxidative stress during the L-DOPA treatment may lead to the gradual degeneration of dopaminergic neurons because the self-oxidation or enzymatic oxidation of L-DOPA may result in the production of reactive oxygen species (ROS), causing damage to neurons, including the residual nigrostriatal dopaminergic neurons [1]
Influence of L-DOPA at Different Concentrations on the Growth of PC12 Cells is Related to the ROS Due to LDOPA Metabolism
Summary
Levodopa (L-DOPA) is the most widely used drug in the treatment of Parkinson’s disease (PD). The clinical evidence for its neurotoxicity is based on the fact that L-DOPA alone can not alleviate PD, the honeymoon of this treatment last only 2–5 years and it may cause adverse effects in the long term treatment. There is still evidence indicating that L-DOPA has no neurotoxicity. In vivo study showed that long-term treatment of high dose L-DOPA did not cause damage to dopaminergic cells, while increased the density of dopaminergic nerve fibers [7,8,9]. In patients whose nigra-striatal system is intact, long-term L-DOPA treatment does not cause any damage to the dopaminergic neurons [10]. A multicenter, randomized, double-blind four-year clinical trial (ELLDOPA) reported the protective effect of L-DOPA in 361 patients with PD [10]
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