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

TitleZ-ligustilide potentiates the cytotoxicity of dopamine in rat dopaminergic PC12 cells
Authors
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
Citation
Neurotoxicity Research, 2012, v. 22 n. 4, p. 345-354 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/152802
ISSN
2014 Impact Factor: 3.538
2014 SCImago Journal Rankings: 1.186
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorQi, Hen_HK
dc.contributor.authorZhao, Jen_HK
dc.contributor.authorHan, Yen_HK
dc.contributor.authorLau, ASYen_HK
dc.contributor.authorRong, Jen_HK
dc.date.accessioned2012-07-16T09:48:41Z-
dc.date.available2012-07-16T09:48:41Z-
dc.date.issued2012en_HK
dc.identifier.citationNeurotoxicity Research, 2012, v. 22 n. 4, p. 345-354en_HK
dc.identifier.issn1029-8428en_HK
dc.identifier.urihttp://hdl.handle.net/10722/152802-
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.en_HK
dc.languageengen_US
dc.publisherSpringer New York LLC. The Journal's web site is located at http://www.springerlink.com/content/1029-8428en_HK
dc.relation.ispartofNeurotoxicity Researchen_HK
dc.rightsThe original publication is available at www.springerlink.com-
dc.subjectCytotoxicityen_HK
dc.subjectDopamineen_HK
dc.subjectParkinson's diseaseen_HK
dc.subjectReactive oxygen speciesen_HK
dc.subjectReduced glutathioneen_HK
dc.titleZ-ligustilide potentiates the cytotoxicity of dopamine in rat dopaminergic PC12 cellsen_HK
dc.typeArticleen_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.emailRong, J: jrong@hku.hken_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.identifier.authorityRong, J=rp00515en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s12640-012-9319-6en_HK
dc.identifier.pmid22451226-
dc.identifier.scopuseid_2-s2.0-84870299180en_HK
dc.identifier.hkuros203763en_US
dc.identifier.volume22-
dc.identifier.issue4-
dc.identifier.spage345en_HK
dc.identifier.epage354en_HK
dc.identifier.eissn1476-3524-
dc.identifier.isiWOS:000308966400009-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridRong, J=7005980047en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK
dc.identifier.scopusauthoridHan, Y=8527680500en_HK
dc.identifier.scopusauthoridZhao, J=55122766600en_HK
dc.identifier.scopusauthoridQi, H=35367105300en_HK

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