| Effect of fraxetin and myricetin on rotenone-induced cytotoxicity in SH-SY5Y cells: comparison with N-acetylcysteine. | |
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MedLine Citation:
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PMID: 12860476 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of this study was to investigate the potential neuroprotective effects of myricetin (flavonoid) and fraxetin (coumarin) on rotenone-induced apoptosis in SH-SY5Y cells, and the possible signal pathway involved in a neuronal cell model of Parkinson's disease. These two compounds were compared to N-acetylcysteine. The viability of cells was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and cytotoxicity was assayed by lactate dehydrogenase (LDH) released into the culture medium. Parameters related to apoptosis, such as caspase-3 activity, the cleavage of poly(ADP-ribose) polymerase and the levels of reactive oxygen species were also determined. Rotenone caused a time- and dose-dependent decrease in cell viability and the degree of LDH release was proportionally to the effects on cell viability. Cells were pretreated with fraxetin, myricetin and N-acetylcysteine at different concentrations for 30 min before exposure to rotenone. Cytotoxicity of rotenone (5 microM) for 16 h was significantly diminished as well as the release of LDH into the medium, by the effect of fraxetin, myricetin and N-acetylcysteine, with fraxetin (100 microM) and N-acetylcysteine (100 microM) being more effective than myricetin (50 microM). Rotenone-induced apoptosis in SH-SY5Y cells was detected by an increase in caspase-3 activity and in the cleavage of poly(ADP-ribose) polymerase. After exposing these cells to rotenone, a significant increase in reactive oxygen species preceded apoptotic events. Fraxetin (100 microM) and N-acetylcysteine (100 microM) not only reduced rotenone-induced reactive oxygen species formation, but also attenuated caspase-3 activity and poly(ADP-ribose) polymerase cleavage at 16 h against rotenone-induced apoptosis. The effect of fraxetin in both experiments was similar to that of N-acetylcysteine. These results demonstrated the protective action of fraxetin and suggest that it can reduce apoptosis, possibly by decreasing free radical generation in SH-SY5Y cells. Myricetin at 100 microM was without any preventive effect. |
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Authors:
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M Francisca Molina-Jimenez; M Isabel Sanchez-Reus; Juana Benedi |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 472 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2003 Jul |
Date Detail:
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Created Date: 2003-07-15 Completed Date: 2004-04-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 81-7 Citation Subset: IM |
Affiliation:
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Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense, Plaza de Ramon y Cajal s/n 28040, Madrid, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcysteine
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pharmacology* Apoptosis / drug effects Caspase 3 Caspases / metabolism Cell Line, Tumor Cell Survival / drug effects Coumarins / pharmacology* Flavonoids / pharmacology* Humans L-Lactate Dehydrogenase / metabolism Neuroblastoma / enzymology, pathology Neuroprotective Agents / pharmacology* Reactive Oxygen Species / metabolism Rotenone / toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Coumarins; 0/Flavonoids; 0/Neuroprotective Agents; 0/Reactive Oxygen Species; 529-44-2/myricetin; 574-84-5/fraxetin; 616-91-1/Acetylcysteine; 83-79-4/Rotenone; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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