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Edaravone protects against MPP + ‐induced cytotoxicity in rat primary cultured astrocytes via inhibition of mitochondrial apoptotic pathway
Author(s) -
Chen Hui,
Wang Sen,
Ding JianHua,
Hu Gang
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05573.x
Subject(s) - apoptosis , edaravone , cytotoxicity , mitochondrion , chemistry , microbiology and biotechnology , pharmacology , biochemistry , biology , in vitro
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 pre‐treatment with Eda inhibited astrocytic apoptosis and lactate dehydrogenase release induced by MPP + (200 μM). Further study revealed that Eda prevented GSH depletion, down‐regulated mRNA expressions of NADPH oxidase membrane subunit gp91 and membrane‐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.