The radical scavenger edaravone prevents oxidative neurotoxicity induced by peroxynitrite and activated microglia.
The free radical scavenger edaravone has been used as an anti-oxidative agent in acute ischemic brain disorders. We examined the effect of edaravone on the production of nitric oxide (NO), reactive oxygen species (ROS) and proinflammatory cytokines by activated microglia, and we also examined its neuroprotective role in cortical neuronal cultures oxidatively stressed by the peroxynitrite donor N-morpholinosydnonimine (SIN-1) or activated microglia. Edaravone significantly suppressed the production of NO and ROS by activated microglia, though it did not suppress production of inflammatory cytokines. In addition, edaravone significantly suppressed neuronal cell death and dendrotoxicity induced by either SIN-1 or activated microglia in a dose-dependent manner. These results suggest that edaravone may function as a neuroprotective agent counteracting oxidative neurotoxicity arising from activated microglia, as occurs in either inflammatory or neurodegenerative disorders of the central nervous system.
Banno
Masahiro
M
Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8601, Japan.
Mizuno
Tetsuya
T
Kato
Hideki
H
Zhang
Guiqin
G
Kawanokuchi
Jun
J
Wang
Jinyan
J
Kuno
Reiko
R
Jin
Shijie
S
Takeuchi
Hideyuki
H
Suzumura
Akio
A
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D030421:Peroxynitrous Acid; D000077553:Edaravone; D000983:Antipyrine