[Effect of mitochondrial membrane potential in the neurotoxicity of artemether].
OBJECTIVE
To study the effect of mitochondrial membrane potential and cellular membrane permeability in the neurotoxicity of artemether.


METHODS
Mitochondrial membrane potential and cellular membrane permeability in pheochromocytoma cell and primary cultured rat neuronal cell were measured by flow cytometry, using rhodamine 123(Rh123) and PI as fluorescent dye, respectively. Mitochondrial swelling was measured by spectrometer.


RESULTS
Artemether could decrease the mitochondrial membrane potential and increase the cellular membrane permeability in both cell types in a dose-dependent manner. In addition, artemether led to mitochondrial swelling with dose-effect and time-effect relationships.


CONCLUSIONS
The decrease of mitochondrial membrane potential plays an important role in the neurotoxicity of artemether. The drug can change the mitochondrial membrane potential and mitochondrial swelling by affecting the permeability transition pore complex located in the mitochondrial membrane, increasing cellular membrane permeability, causing an obstruction and finally leading to neurotoxicity.
Zhao
Yan-hong
YH
Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071.
Wang
Jing-yan
JY
D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D000077549:Artemether; D037621:Artemisinins / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000633:toxicity*
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077549:Artemether