| Z-Ligustilide Potentiates the Cytotoxicity of Dopamine in Rat Dopaminergic PC12 Cells. | |
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MedLine Citation:
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PMID: 22451226 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hongyi Qi; Jia Zhao; Yifan Han; Allan S Y Lau; Jianhui Rong |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-27 |
Journal Detail:
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Title: Neurotoxicity research Volume: - ISSN: 1476-3524 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100929017 Medline TA: Neurotox Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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