PMID- 19201991
OWN - NLM
STAT- MEDLINE
DCOM- 20090522
LR  - 20181201
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Linking)
VI  - 329
IP  - 2
DP  - 2009 May
TI  - Edaravone, a free radical scavenger, protects against retinal damage in vitro and 
      in vivo.
PG  - 687-98
LID - 10.1124/jpet.108.148676 [doi]
AB  - Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is 
      used for the treatment of acute cerebral infarction. In this study, we 
      investigated whether edaravone is neuroprotective against retinal damage. In 
      vitro, we used a radical-scavenging capacity assay using reactive oxygen 
      species-sensitive probes to investigate the effects of edaravone on H(2)O(2), 
      superoxide anion (O(2)*), and hydroxyl radical (*OH) production in a rat retinal 
      ganglion cell line (RGC-5). The effect of edaravone on oxygen-glucose deprivation 
      (OGD)-induced RGC-5 damage was evaluated using a 
      2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, 
      monosodium salt assay of cell viability. Edaravone 
      (3-methyl-1-phenyl-2-pyrazolin-5-one) significantly decreased radical generation 
      and reduced the cell death induced by OGD stress. In vivo, retinal damage was 
      induced by intravitreous injection of N-methyl-D-aspartate (NMDA; 5 nmol) and was 
      evaluated by examining ganglion cell layer cell loss, terminal deoxynucleotidyl 
      transferase dUTP nick-end labeling (TUNEL) staining, and the expressions of two 
      oxidant-stress markers [4-hydroxy-2-nonenal (4-HNE) and 
      8-hydroxy-2-deoxyguanosine (8-OHdG)]. In addition, activations of 
      mitogen-activated protein kinases (MAPKs) [extracellular signal-regulated protein 
      kinases (ERK), c-Jun NH(2)-terminal kinases (JNK), and p38 MAPK], as downstream 
      signal pathways after NMDA receptor activation, were measured using 
      immunoblotting and immunostaining. Edaravone at 5 and 50 nmol intravitreous 
      injection or at 1 and 3 mg/kg i.v. significantly protected against NMDA-induced 
      retinal cell death. At 50 nmol intravitreous injection, it 1) decreased the 
      retinal expressions of TUNEL-positive cells, 4-HNE, and 8-OHdG and 2) reduced the 
      retinal expressions of NMDA-induced phosphorylated JNK and phosphorylated p38 but 
      not that of phosphorylated ERK. These findings suggest that oxidative stress 
      plays a pivotal role in retinal damage and that edaravone may be a candidate for 
      the effective treatment of retinal diseases.
FAU - Inokuchi, Yuta
AU  - Inokuchi Y
AD  - Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Imai, Shunsuke
AU  - Imai S
FAU - Nakajima, Yoshimi
AU  - Nakajima Y
FAU - Shimazawa, Masamitsu
AU  - Shimazawa M
FAU - Aihara, Makoto
AU  - Aihara M
FAU - Araie, Makoto
AU  - Araie M
FAU - Hara, Hideaki
AU  - Hara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090206
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Culture Media)
RN  - 0 (Cyan Fluorescent Protein)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Free Radicals)
RN  - 0 (Thy-1 Antigens)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - S798V6YJRP (Edaravone)
RN  - T3CHA1B51H (Antipyrine)
SB  - IM
MH  - Animals
MH  - Antipyrine/administration & dosage/*analogs & 
      derivatives/pharmacology/therapeutic use
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Culture Media
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Edaravone
MH  - Free Radical Scavengers/administration & dosage/*pharmacology/therapeutic use
MH  - Free Radicals/*metabolism
MH  - Green Fluorescent Proteins/genetics
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - N-Methylaspartate
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Retinal Diseases/genetics/metabolism/pathology/*prevention & control
MH  - Retinal Ganglion Cells/*drug effects/metabolism/pathology
MH  - Thy-1 Antigens/genetics
EDAT- 2009/02/10 09:00
MHDA- 2009/05/23 09:00
CRDT- 2009/02/10 09:00
PHST- 2009/02/10 09:00 [entrez]
PHST- 2009/02/10 09:00 [pubmed]
PHST- 2009/05/23 09:00 [medline]
AID - jpet.108.148676 [pii]
AID - 10.1124/jpet.108.148676 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2009 May;329(2):687-98. doi: 10.1124/jpet.108.148676. Epub 
      2009 Feb 6.