Edaravone Inhibits DNA Peroxidation and Neuronal Cell Death in Neonatal Hypoxic-Ischemic Encephalopathy Model Rat

Abstract

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-2Ј-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.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

“…Since DNA damage induced by radiation is the result of the generation of ROS, a compound with antioxidant potential can scavenge ROS and ameliorate DNA damage. Edaravone is known to enhance DNA repair mechanisms and inhibit DNA strand breaks against ROS (Takizawa et al 2009). Many synthetic compounds have been investigated in the recent past; nonetheless, the ones that are currently available present many drawbacks including high cost, undesirable side effects, and toxicity (Maurya et al 2006).…”

Edaravone Protects Against Apoptotic Neuronal Cell Death and Improves Cerebral Function After Traumatic Brain Injury in Rats

“…The early stage change of poly(ADP-ribose) polymerase, a DNA repair-associated enzyme, is similar to that of 8-OHdG [22,23]. An overexpression of poly(ADP-ribose) polymerase with cleaved casepase-3 appearance has been shown to occur at 24 h after a brain insult, and then end at 72 h [22,24]. Although in dividing cells, damaged DNA is enzymatically repaired with or without 8-OHdG production, post-mitotic cells such as neurons show low enzyme activity for DNA repair and are quite vulnerable to a brain insult [22,24].…”

“…2 and 3). The early stage change of poly(ADP-ribose) polymerase, a DNA repair-associated enzyme, is similar to that of 8-OHdG [22,23]. An overexpression of poly(ADP-ribose) polymerase with cleaved casepase-3 appearance has been shown to occur at 24 h after a brain insult, and then end at 72 h [22,24].…”

“…An overexpression of poly(ADP-ribose) polymerase with cleaved casepase-3 appearance has been shown to occur at 24 h after a brain insult, and then end at 72 h [22,24]. Although in dividing cells, damaged DNA is enzymatically repaired with or without 8-OHdG production, post-mitotic cells such as neurons show low enzyme activity for DNA repair and are quite vulnerable to a brain insult [22,24]. Such vulnerable neurons died by DNA repair dysfunction, DNA fragmentation, and apoptosis [22,24].…”

Recent Information on the Pathogenesis and Treatment of Hypoxic-Ischemic Brain Lesions in Newborns

“…В Японии он уже используется в клинике у взрослых при лечении острой стадии инсульта [175]. Эдаравон, как полага-ют, взаимодействует с перекисными и гидроксильными радикалами, создавая промежуточные формы, которые образуют стабильные (устойчивые) конечные продук-ты окисления, предотвращая таким образом воздей-ствие свободных радикалов при оксидантном стрессе [176,177]. Системное введение эдаравона в течение 30 мин после реанимации при ГИП может спасти ней-роны в стриатуме, что было показано американскими учеными на животной модели новорожденных с ГИП (в этой работе показана также эффективность другого антиоксиданта -EUK-134) [178].…”