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Protective Effect of Fangchinoline on Cyanide-Induced Neuro-toxicity in Cultured Rat Cerebellar Granule Cells  

Cho, Soon-Ok (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Seong, Yeon-Hee (College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University)
Publication Information
Archives of Pharmacal Research / v.25, no.3, 2002 , pp. 349-356 More about this Journal
Abstract
The present study was performed to examine the effect of fangchinoline, a bis- benzylisoquinoline alkaloid, which exhibits the characteristics of a $Ca^{2+}$ channel blocker, on cyanide-induced neurotoxicity using cultured rat cerebellar granule neurons. NaCN produced a concentration-dependent reduction of cell viability, which was blocked by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, verapamil, L-type$Ca^{2+}$channel blocker, and L-NAME, a nitric oxide synthase inhibitor. Pretreatment with fangchinoline over a concentration range of 0.1 to 10 $\mu$M significantly decreased the NaCN-induced neuronal cell death, glutamate release into medium, and elevation of $[Ca^{2+}]_i$ and oxidants generation. These results suggest that fangchinoline may mitigate the harmful effects of cyanide-induced neuronal cell death by interfering with $[Ca^{2+}]_i$influx, due to its function as a $Ca^{2+}$ channel blocker, and then by inhibiting glutamate release and oxidants generation.
Keywords
Fangchinoline; NaCN; Neurotoxicity; $Ca^{2+}$ channel antagonist; Cerebellar granule cells;
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