Protective effect of fangchinoline on cyanide-induced neurotoxicity in cultured rat cerebellar granule cells.
The present study was performed to examine the effect of fangchinoline, a bis- benzylisoquinoline alkaloid, which exhibits the characteristics of a Ca2+ 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 Ca2+ channel blocker, and L-NAME, a nitric oxide synthase inhibitor. Pretreatment with fangchinoline over a concentration range of 0.1 to 10 microM significantly decreased the NaCN-induced neuronal cell death, glutamate release into medium, and elevation of [Ca2+]i and oxidants generation. These results suggest that fangchinoline may mitigate the harmful effects of cyanide-induced neuronal cell death by interfering with [Ca2+]i influx, due to its function as a Ca2+ channel blocker, and then by inhibiting glutamate release and oxidants generation.
Cho
Soon Ok
SO
College of Veterinary Medicine and Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.
Seong
Yeon Hee
YH
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D044182:Benzylisoquinolines; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D004396:Coloring Agents; D003486:Cyanides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003594:Cytoplasmic Granules / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000517:prevention & control*; D016877:Oxidants / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D031607:Stephania / Q000737:chemistry; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue
D000470:Alkaloids; D000975:Antioxidants; D044182:Benzylisoquinolines; D004396:Coloring Agents; D003486:Cyanides; D016877:Oxidants; D013778:Tetrazolium Salts; D013844:Thiazoles; D018698:Glutamic Acid; C060802:fangchinoline; C022616:thiazolyl blue; D014343:Trypan Blue; D002118:Calcium