Study of neurotoxic effects and underlying mechanisms of aconitine on cerebral cortex neuron cells.
The study investigated the neurotoxiceffects and underlying mechanisms of aconitine on cerebral cortex neuron cells prepared from neonatal SD rats. The uniform design and MTT method were applied to study the effect of aconitine with different concentrations at scheduled time. The influence of aconitine at the maximal toxicity concentration was observed using optical microscope and electron microscope. The influences of aconitine on neuron cells membrane, neuron cells' inner balance, energy metabolism and neurotransmitters were observed to investigate the action mechanisms of aconitine. The results indicated that the maximal toxicity-concentration was 2% and the critical time were 30 s, 1 min and 20 min respectively. The effects of aconitine on neuron cells' morphology included cells synapse's fracture, cells membrane fragment, mitochondria's swell, cytoplasmic vacuoles, nuclear chromatin's condensation and accumulation. The stability of biomembrane, the internal milieu and the energy metabolism were also disturbed with the increase of activity of LDH and concentration of neurotransmitters (acetylcholine, opioid, catecholamine and SP) in culture medium, the increase of the activity of ACP and [Na+], [Ca2+] concentration, and the decrease of Na(+)-K(+)-ATP, [K+], [Mg2+] and glycogen concentration in the cells. Toxic mechanisms of aconitine damaging neuron cells may be because it inhibited the activity of Na(+)-K(+)-ATP, influenced the concentrations of [Na+], [K+], [Ca2+], [Mg2+] and neurotransmitters in the cells, which resulted in the injuries of cells' morphology and function.
Peng
Cheng
C
Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 670075, China. pengchengchengdu@126.com
Zheng
Tao
T
Yang
Fan
F
Li
Yun-Xia
YX
Zhang
Ding-Kun
DK
D000157:Aconitine / Q000008:administration & dosage / Q000633:toxicity*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
D000276:Adjuvants, Immunologic; D018377:Neurotransmitter Agents; D007770:L-Lactate Dehydrogenase; D000254:Sodium-Potassium-Exchanging ATPase; D000157:Aconitine