Z-ligustilide potentiates the cytotoxicity of dopamine in rat dopaminergic PC12 cells

Hongyi Qi, Jia Zhao, Yifan Han, Allan S.Y. Lau, Jianhui Rong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

11 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)345-354
Number of pages10
JournalNeurotoxicity Research
Volume22
Issue number4
DOIs
Publication statusPublished - 1 Nov 2012

Keywords

  • Cytotoxicity
  • Dopamine
  • Parkinson's disease
  • Reactive oxygen species
  • Reduced glutathione
  • Z-Ligustilide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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