Iron-chelating Edaravone For Retinal Diseases

Edaravone, a free radical scavenger, protects against retinal damage
in vitro and in vivo.
J Pharmacol Exp Ther. 2009 Feb 6.
Inokuchi Y, Imai S, Nakajima Y, Shimazawa M, Aihara M, Araie M, Hara
H.
Gifu Pharmaceutical University.

Edaravone, a free radical scavenger, is used for the treatment of
acute cerebral infarction.
In this study, we investigated whether edaravone is neuroprotective
against on retinal damage.
In vitro, we employed a radical scavenging-capacity assay using
reactive oxygen species (ROS)-sensitive probes to investigate the
effects of edaravone on hydrogen peroxide (H2O2), superoxide anion (O2.
(-)), 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 WST-8
assay of cell viability.
Edaravone 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 (GCL) cell loss, 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 MAPKs [extracellular signal regulated
protein kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 MAPK],
as down stream signal pathways after NMDA-receptor activation, were
measured using immunoblotting and immunostaining.
Edaravone at 5 and 50 nmol (intravitreously) or at 1 and 3 mg/kg
(i.v.) significantly protected against NMDA-induced retinal cell
death. At 50 nmol (intravitreously) it : (a) decreased the retinal
expressions of TUNEL-positive cells, 4-HNE, and 8-OHdG and (b) 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.

PMID: 19201991
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http://tinyurl.com/ynpdhm


"Iron-chelating agents, N-acetyl-L-cysteine (NAC), apocynin,probucol,
and edaravone, are useful in preventing cardiovascular injury and
diseases."


Recent Patents on Anti-Infective Drug Discovery, 2006, 1,
17-31171574-891X/06 $100.00+.00(c) 2006 Bentham Science Publishers
Ltd.Recent Progress in Pharmacological Research of Antioxidants
inPathological Conditions: Cardiovascular Health


--------------------------


Cardiovasc Ther. 2008 Summer;26(2):101-14.


The novel antioxidant edaravone: from bench to bedside.


Watanabe T, Tahara M, Todo S.


Department of REDOX Medicinal Science, Graduate School of
Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.


Over the last decade, important advances have been made to support
the
fact that reactive oxygen species (ROS) are generated and play a
harmful role during the acute and late stages of cerebral ischemia.
Several drugs, such as radical scavengers and antioxidants, have been
evaluated in preclinical and clinical studies.
Edaravone (3-methyl-1- phenyl-2-pyrazolin-5-one; Radicut((R)),
Mitsubishi Tanabe Pharma Corporation) is a novel antioxidant that is
currently used in Japan for the treatment of patients in the acute
stage of cerebral infarction.
Edaravone scavenges ROS and inhibits proinflammatory responses after
brain ischemia in animals and humans.
In particular, postischemic inflammation, leading to brain edema and
infarction due to neuronal damage and endothelial cell death, can
be ameliorated by edaravone.
In addition to these antistroke effects, edaravone has also
been shown to prevent oxidative damage to various extracerebral
organs.
Therefore, in addition to its usefulness in the treatment of
stroke, edaravone is expected to play an integral role in the
treatment of many oxidative stress-related diseases.

PMID: 18485133
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