PMID- 22362184
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20190911
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 118
IP  - 3
DP  - 2012
TI  - Role of oxidative stress in retinal photoreceptor cell death in 
      N-methyl-N-nitrosourea-treated mice.
PG  - 351-62
AB  - This study aimed to investigate whether oxidative stress contributes to retinal 
      cell death in a mouse model of photoreceptor degeneration induced by 
      N-methyl-N-nitrosourea (MNU). We measured in vitro MNU-induced radical production 
      in retinal cell cultures of murine 661W photoreceptor-derived cells; RGC-5, a 
      mouse ganglion cell line; and primary retinal cells. The addition of MNU induced 
      oxidative radical generation in 661W and primary retinal cells, but not in RGC-5 
      cells. Edaravone, a free radical scavenger, at 1 microM reduced MNU-induced radical 
      production in 661W and primary retinal cells. To induce in vivo retinal 
      photoreceptor degeneration in mice, we administered 60 mg/kg MNU by 
      intraperitoneal injection. We intravenously administered 1 mg/kg edaravone 
      immediately and at 6 h after the MNU injection. Retinal photoreceptor 
      degeneration was evaluated by measuring the thickness of the outer nuclear layer 
      (ONL) by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) 
      staining and by oxidative stress markers. MNU caused photoreceptor cell loss at 7 
      days after administration. Edaravone inhibited ONL thinning and reduced 
      TUNEL-positive cells and the oxidative stress markers. These findings indicate 
      that MNU leads to selective photoreceptor degradation via oxidative stress in 
      vitro and in vivo and may help to understand the pathogenic mechanism of 
      retinitis pigmentosa.
FAU - Tsuruma, Kazuhiro
AU  - Tsuruma K
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
FAU - Yamauchi, Mika
AU  - Yamauchi M
FAU - Inokuchi, Yuta
AU  - Inokuchi Y
FAU - Sugitani, Sou
AU  - Sugitani S
FAU - Shimazawa, Masamitsu
AU  - Shimazawa M
FAU - Hara, Hideaki
AU  - Hara H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120223
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Alkylating Agents)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Reactive Oxygen Species)
RN  - 684-93-5 (Methylnitrosourea)
RN  - S798V6YJRP (Edaravone)
RN  - T3CHA1B51H (Antipyrine)
SB  - IM
MH  - Alkylating Agents/*toxicity
MH  - Animals
MH  - Antipyrine/analogs & derivatives/pharmacology
MH  - Cell Death/drug effects
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Edaravone
MH  - Free Radical Scavengers/pharmacology
MH  - Male
MH  - Methylnitrosourea/*toxicity
MH  - Mice
MH  - Oxidative Stress/*drug effects
MH  - Photoreceptor Cells, Vertebrate/*drug effects/metabolism/pathology
MH  - Reactive Oxygen Species/metabolism
EDAT- 2012/03/01 06:00
MHDA- 2012/09/11 06:00
CRDT- 2012/02/25 06:00
PHST- 2012/02/25 06:00 [entrez]
PHST- 2012/03/01 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
AID - JST.JSTAGE/jphs/11110FP [pii]
AID - 10.1254/jphs.11110fp [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2012;118(3):351-62. doi: 10.1254/jphs.11110fp. Epub 2012 Feb 23.