Edaravone protects against MPP+-induced cytotoxicity in rat primary cultured astrocytes via inhibition of mitochondrial apoptotic pathway

Edaravone (Eda) is a potent scavenger of hydroxyl radicals and has been demonstrated to be beneficial for patients with acute ischemic stroke. This study was set out to investigate whether Eda protect against MPP+-induced cytotoxicity in rat primary cultured astrocytes. The results showed that pretreatment with Eda inhibited astrocytic apoptosis and lactate dehydrogenase release induced by MPP+ (200 mu M). Further study revealed that Eda prevented GSH depletion, down-regulated mRNA expressions of NADPH oxidase membrane subunit gp91 and m em bran e-translocated subunit p47, and prevented the decreases of state 3 respiration respiration and respiratory control ratio induced by MPP+, and thereby inhibited reactive oxygen species production evoked by MPP+. Moreover, Eda could ameliorate mitochondrial respiratory function, restrain, and prevent mitochondrial membrane potential loss induced by MPP+. Consequently, Eda inhibited releases of cytochrome c and apoptosis-inducing factor induced by MPP+. Taken together, these findings reveal for the first time that Eda protects against MPP+-induced astrocytic apoptosis via decreasing intracellular reactive oxygen species level and subsequently inhibiting mitochondrial apoptotic pathway. The antiapoptosis effects of Eda on astrocytes may provide a new perspective on neuroprotective therapy.