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

Eur J Pharmacol. 2004 Mar 19;488(1-3):71-7. doi: 10.1016/j.ejphar.2004.02.021.

Abstract

(1R,9S)-beta-Hydrastine in lower concentrations of 10-50 microM inhibits dopamine biosynthesis in PC12 cells. In this study, the effects of (1R,9S)-beta-hydrastine on L-DOPA (L-3,4-dihydroxyphenylalanine)-induced cytotoxicity in PC12 cells were investigated. (1R,9S)-Hydrastine at concentrations up to 250 microM did not reduce cell viability. However, at concentrations higher than 500 microM 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 (1R,9S)-beta-hydrastine (500 and 750 microM) in combination with L-DOPA (20, 50 and 100 microM) after 24 or 48 h resulted in a significant decrease in cell viability compared with the effects of (1R,9S)-beta-hydrastine or L-DOPA alone, and apoptotic cell death was observed. However, the decrease in cell viability induced by (1R,9S)-beta-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 (1R,9S)-beta-hydrastine has a mild cytotoxic effect and at higher concentration ranges aggravates L-DOPA-induced cytotoxicity in PC12 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Alkaloids / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Benzylisoquinolines
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • DNA Fragmentation / drug effects
  • Dopamine Agents / pharmacology*
  • Flow Cytometry
  • Free Radical Scavengers / pharmacology
  • Isomerism
  • Levodopa / pharmacology*
  • PC12 Cells
  • Rats

Substances

  • Alkaloids
  • Antioxidants
  • Benzylisoquinolines
  • Dopamine Agents
  • Free Radical Scavengers
  • Levodopa
  • hydrastine
  • Acetylcysteine