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Article: Z-ligustilide potentiates the cytotoxicity of dopamine in rat dopaminergic PC12 cells
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TitleZ-ligustilide potentiates the cytotoxicity of dopamine in rat dopaminergic PC12 cells
 
AuthorsQi, H1
Zhao, J1
Han, Y2
Lau, ASY1
Rong, J1
 
KeywordsCytotoxicity
Dopamine
Parkinson's disease
Reactive oxygen species
Reduced glutathione
 
Issue Date2012
 
PublisherSpringer New York LLC. The Journal's web site is located at http://www.springerlink.com/content/1029-8428
 
CitationNeurotoxicity Research, 2012, v. 22 n. 4, p. 345-354 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s12640-012-9319-6
 
AbstractDopamine 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.
 
ISSN1029-8428
2013 Impact Factor: 3.151
2013 SCImago Journal Rankings: 1.426
 
DOIhttp://dx.doi.org/10.1007/s12640-012-9319-6
 
ISI Accession Number IDWOS:000308966400009
 
DC FieldValue
dc.contributor.authorQi, H
 
dc.contributor.authorZhao, J
 
dc.contributor.authorHan, Y
 
dc.contributor.authorLau, ASY
 
dc.contributor.authorRong, J
 
dc.date.accessioned2012-07-16T09:48:41Z
 
dc.date.available2012-07-16T09:48:41Z
 
dc.date.issued2012
 
dc.description.abstractDopamine 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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationNeurotoxicity Research, 2012, v. 22 n. 4, p. 345-354 [How to Cite?]
DOI: http://dx.doi.org/10.1007/s12640-012-9319-6
 
dc.identifier.doihttp://dx.doi.org/10.1007/s12640-012-9319-6
 
dc.identifier.eissn1476-3524
 
dc.identifier.epage354
 
dc.identifier.hkuros203763
 
dc.identifier.isiWOS:000308966400009
 
dc.identifier.issn1029-8428
2013 Impact Factor: 3.151
2013 SCImago Journal Rankings: 1.426
 
dc.identifier.issue4
 
dc.identifier.pmid22451226
 
dc.identifier.scopuseid_2-s2.0-84870299180
 
dc.identifier.spage345
 
dc.identifier.urihttp://hdl.handle.net/10722/152802
 
dc.identifier.volume22
 
dc.languageeng
 
dc.publisherSpringer New York LLC. The Journal's web site is located at http://www.springerlink.com/content/1029-8428
 
dc.publisher.placeUnited States
 
dc.relation.ispartofNeurotoxicity Research
 
dc.rightsThe original publication is available at www.springerlink.com
 
dc.subjectCytotoxicity
 
dc.subjectDopamine
 
dc.subjectParkinson's disease
 
dc.subjectReactive oxygen species
 
dc.subjectReduced glutathione
 
dc.titleZ-ligustilide potentiates the cytotoxicity of dopamine in rat dopaminergic PC12 cells
 
dc.typeArticle
 
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<item><contributor.author>Qi, H</contributor.author>
<contributor.author>Zhao, J</contributor.author>
<contributor.author>Han, Y</contributor.author>
<contributor.author>Lau, ASY</contributor.author>
<contributor.author>Rong, J</contributor.author>
<date.accessioned>2012-07-16T09:48:41Z</date.accessioned>
<date.available>2012-07-16T09:48:41Z</date.available>
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<description.abstract>Dopamine toxicity is an ongoing controversy surrounding the use of levadopa (L-Dopa) in the therapy of Parkinson&apos;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&apos;s disease.</description.abstract>
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<subject>Cytotoxicity</subject>
<subject>Dopamine</subject>
<subject>Parkinson&apos;s disease</subject>
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<subject>Reduced glutathione</subject>
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Hong Kong Polytechnic University