Effects of (1 R,9 S)-β-hydrastine on l-DOPA-induced cytotoxicity in PC12 cells

(1 R,9 S)-β-Hydrastine in lower concentrations of 10–50 μM inhibits dopamine biosynthesis in PC12 cells (Planta Med. 57 (2001) 609). In this study, the effects of (1 R,9 S)-β-hydrastine on l-DOPA ( l-3,4-dihydroxyphenylalanine)-induced cytotoxicity in PC12 cells were investigated. (1 R,9 S)-Hydrasti...

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Published in:European journal of pharmacology 2004-03, Vol.488 (1), p.71-77
Main Authors: Yin, Shou Yu, Lee, Jae Joon, Kim, Yu Mi, Jin, Chun Mei, Yang, Yoo Jung, Kang, Min Hee, Kai, Masaaki, Lee, Myung Koo
Format: Article
Language:English
Subjects:
(1 R,9 S)-β-Hydrastine
Acetylcysteine - pharmacology
Alkaloids - pharmacology
Animals
Antioxidants - pharmacology
Apoptosis
Apoptosis - drug effects
Benzylisoquinolines
Cell Death - drug effects
Cell Survival - drug effects
Cytotoxicity
DNA Fragmentation - drug effects
Dopamine Agents - pharmacology
Flow Cytometry
Free Radical Scavengers - pharmacology
Isomerism
l-DOPA ( l-3,4-dihydroxyphenylalanine)
Levodopa - pharmacology
PC12 cell
PC12 Cells
Rats
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Summary:(1 R,9 S)-β-Hydrastine in lower concentrations of 10–50 μM inhibits dopamine biosynthesis in PC12 cells (Planta Med. 57 (2001) 609). In this study, the effects of (1 R,9 S)-β-hydrastine on l-DOPA ( l-3,4-dihydroxyphenylalanine)-induced cytotoxicity in PC12 cells were investigated. (1 R,9 S)-Hydrastine at concentrations up to 250 μM did not reduce cell viability. However, at concentrations higher than 500 μM it caused cytotoxicity in PC12 cells, as determined with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, TUNEL (terminal deoxynucleotidyltransferase dUTP nick-end labeling) method and flow cytometry. Exposure of PC12 cells to cytotoxic concentrations of (1 R,9 S)-β-hydrastine (500 and 750 μM) in combination with l-DOPA (20, 50 and 100 μM) after 24 or 48 h resulted in a significant decrease in cell viability compared with the effects of (1 R,9 S)-β-hydrastine or l-DOPA alone, and apoptotic cell death was observed. However, the decrease in cell viability induced by (1 R,9 S)-β-hydrastine was not prevented by the antioxidant N-acetyl- l-cysteine, indicating that it is not mediated by membrane-based oxygen free radical damage. These data suggest that (1 R,9 S)-β-hydrastine has a mild cytotoxic effect and at higher concentration ranges aggravates l-DOPA-induced cytotoxicity in PC12 cells.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2004.02.021