PMID- 22760072
OWN - NLM
STAT- MEDLINE
DCOM- 20121217
LR  - 20211203
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 690
IP  - 1-3
DP  - 2012 Sep 5
TI  - Oral administration of crocetin prevents inner retinal damage induced by 
      N-methyl-D-aspartate in mice.
PG  - 84-9
LID - 10.1016/j.ejphar.2012.06.035 [doi]
AB  - Crocetin, an aglycone of crocin, is found in stigmas of the saffron crocus 
      (Crocus starus L.) and has been used in traditional medicine. We investigated the 
      effects of oral administration of crocetin on damage induced by 
      N-methyl-D-aspartate (NMDA) in the murine retina. Crocetin was orally 
      administered before and after intravitreal injection of NMDA. A histological 
      analysis was conducted by counting the cell number of ganglion cell layer (GCL). 
      Cell apoptosis was assessed by counting cells positive for terminal 
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Retinal functions 
      were measured in terms of a- and b-wave amplitudes using an electroretinogram 
      (ERG). Activation of caspase-3/7 and cleaved caspase-3 expression were assayed. 
      Calpain activity was evaluated by immunoblotting assays for proteolysis of 
      alpha-spectrin. NMDA injection decreased the cell number in the GCL, and crocetin at 
      a dose of 100 mg/kg inhibited this reduction. TUNEL-positive cells were observed 
      in both GCL and inner nuclear layer (INL) after NMDA injection, and crocetin 
      inhibited the increase in number of TUNEL-positive cells. ERG analysis showed 
      that both a- and b-wave amplitudes were decreased by NMDA injection. Crocetin 
      inhibited the reduction in the b-wave amplitude, but not in the a-wave. NMDA 
      injection activated caspase-3/7 and increased expression of cleaved caspsase-3 in 
      the GCL and INL, but both of these processes were inhibited by crocetin. NMDA 
      injection also induced cleavage of alpha-spectrin, but crocetin did not affect this 
      process. These findings indicate that oral administration of crocetin prevented 
      NMDA-induced retinal damage via inhibition of the caspase pathway.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Ohno, Yuta
AU  - Ohno Y
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
FAU - Nakanishi, Tomohiro
AU  - Nakanishi T
FAU - Umigai, Naofumi
AU  - Umigai N
FAU - Tsuruma, Kazuhiro
AU  - Tsuruma K
FAU - Shimazawa, Masamitsu
AU  - Shimazawa M
FAU - Hara, Hideaki
AU  - Hara H
LA  - eng
PT  - Journal Article
DEP - 20120701
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (trans-sodium crocetinate)
RN  - 11103-57-4 (Vitamin A)
RN  - 36-88-4 (Carotenoids)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - EC 3.4.22.- (Calpain)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Calpain/biosynthesis
MH  - Carotenoids/*administration & dosage
MH  - Caspase 3/biosynthesis
MH  - Cell Count
MH  - Cytoprotection/drug effects
MH  - Enzyme Induction/drug effects
MH  - Male
MH  - Mice
MH  - N-Methylaspartate/*adverse effects
MH  - Retina/*drug effects/*injuries/metabolism/pathology
MH  - Retinal Ganglion Cells/drug effects/metabolism/pathology
MH  - Vitamin A/analogs & derivatives
EDAT- 2012/07/05 06:00
MHDA- 2012/12/18 06:00
CRDT- 2012/07/05 06:00
PHST- 2012/03/17 00:00 [received]
PHST- 2012/06/16 00:00 [revised]
PHST- 2012/06/20 00:00 [accepted]
PHST- 2012/07/05 06:00 [entrez]
PHST- 2012/07/05 06:00 [pubmed]
PHST- 2012/12/18 06:00 [medline]
AID - S0014-2999(12)00547-X [pii]
AID - 10.1016/j.ejphar.2012.06.035 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2012 Sep 5;690(1-3):84-9. doi: 10.1016/j.ejphar.2012.06.035. 
      Epub 2012 Jul 1.