Edaravone inhibits DNA peroxidation and neuronal cell death in neonatal hypoxic-ischemic encephalopathy model rat.
Neonatal hypoxic-ischemic encephalopathy (HIE) is the most frequent neurologic disease in the perinatal period. Its major cause is oxidative stress, which induces DNA peroxidation and apoptotic neuronal death. We examined 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression to evaluate brain damage in neonatal HIE and the therapeutic effect of edaravone, a free radical scavenger. Using HPLC and immunohistochemistry, the 8-OHdG levels of neonatal HIE model Sprague-Dawley rats that were subjected to left common carotid artery ligation and 2-h hypoxia significantly increased after 24-48 h of hypoxic-ischemic (HI) insult, but decreased after 72 h. Moreover, the number of apoptotic cells with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and karyorrhexis significantly increased after 24-72 h of HI insult. In a therapeutic experiment, edaravone was administered i.p. (9 mg/kg) after HI insult every 24 h. Edaravone reduced both the apoptotic neuronal cell number and 8-OHdG expression after 24-48 h of HI. From a double immunofluorescent study, DNA peroxidation occurred in apoptotic neuronal cells with 8-OHdG expression. Edaravone may inhibit the number of apoptotic neuronal cells and 8-OHdG expression within 48 h after HI insult.
Takizawa
Yuji
Y
Department of Mental Retardation and Birth Defect Research, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Miyazawa
Takahito
T
Nonoyama
Shigeaki
S
Goto
Yu-Ichi
Y
Itoh
Masayuki
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
C057755:DNA hydroperoxide; D016166:Free Radical Scavengers; D010545:Peroxides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D000077553:Edaravone; D000983:Antipyrine