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Z-Ligustilide Potentiates the Cytotoxicity of Dopamine in Rat Dopaminergic PC12 Cells.
MedLine Citation:
PMID:  22451226     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Dopamine toxicity is an ongoing controversy surrounding the use of levadopa (L: -Dopa) in the therapy of Parkinson's disease. The initial objective of this study was to investigate the potential of neuroprotective botanicals such as Z-ligustilide in reducing the cytotoxicity of dopamine. We surprisingly found that Z-ligustilide potentiated dopamine toxicity in a dopaminergic cell specific manner. Using rat dopaminergic cell line PC12 as a model, we demonstrated that dopamine and Z-ligustilide in combination profoundly induced cell death, although these drugs alone, to a lesser extent, affected the cell viability in a concentration-dependent manner. The synergistic cytotoxicity of dopamine and Z-ligustilide is likely mediated via apoptosis, characterized by DNA fragmentation and chromatin shrinking after 12 h incubation. By measuring the intracellular reactive oxygen species (ROS) and reduced glutathione (GSH), Z-ligustilide and dopamine in combination dramatically enhanced the ROS formation and further depleted reduced GSH, whereas these drugs alone showed much less activity. Importantly, the synergistic cytotoxicity of dopamine and Z-ligustilide could be largely prevented by thiol-containing antioxidant N-acetylcysteine and GSH other than vitamin C and Trolox. Since the cytotoxicity of Z-ligustilide was not reported previously, the results of this study should raise public concerns over the potential risk associated with the combined use of herbal medicines containing Z-ligustilide with L: -Dopa in the therapy of Parkinson's disease.
Authors:
Hongyi Qi; Jia Zhao; Yifan Han; Allan S Y Lau; Jianhui Rong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-27
Journal Detail:
Title:  Neurotoxicity research     Volume:  -     ISSN:  1476-3524     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100929017     Medline TA:  Neurotox Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong.
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