Mechanism study of Aconitum-induced neurotoxicity in PC12 cells: involvement of dopamine release and oxidative damage.
The Aconitum has been widely used as an important component in traditional Chinese medicine. However, it can cause neurotoxicity, and the mechanism has not been fully elucidated. The present study aimed to investigate the potential dopaminergic neurotoxicity of Aconitum and its mechanism. We found that Aconitum significantly evoked dopamine release from cultured PC12 cells and from the nucleus accubens of mice. These results show that Aconitum can promptly trigger dopamine release both in vitro and in vivo. Aconitum exposure induced reactive oxygen species formation with the decrease of superoxide dismutase and glutathione peroxidase. Moreover, PC12 cells proliferation was inhibited and apoptotic death was detected after Aconitum treatment, but this effect could be attenuated by antioxidants. These findings suggest that Aconitum can damage PC12 cells through oxidative stress mechanism. In conclusion, our results indicate that Aconitum can evoke dopamine release from dopaminergic neurons; excessive extracellular of dopamine can then create stresses on cellular antioxidant systems and induce neuron apoptosis.
Zhao
Yinglan
Y
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Bu
Qian
Q
Zhou
Yan
Y
Lv
Lei
L
Yan
Guangyan
G
Chen
Bo
B
Wang
Li
L
Cen
Xiaobo
X
D031841:Aconitum / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D018517:Plant Roots / Q000633:toxicity; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D004298:Dopamine