Abstract
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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This work was supported by the Seed Funding for Basic Research (University of Hong Kong) (to J.R.).
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Qi, H., Zhao, J., Han, Y. et al. Z-Ligustilide Potentiates the Cytotoxicity of Dopamine in Rat Dopaminergic PC12 Cells. Neurotox Res 22, 345–354 (2012). https://doi.org/10.1007/s12640-012-9319-6
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DOI: https://doi.org/10.1007/s12640-012-9319-6