Neuroprotective effects of edaravone-administration on 6-OHDA-treated
dopaminergic neurons
Wen Ji Yuan , Takao Yasuhara , Tetsuro ****ngo , Kenichiro Muraoka ,
Masahiro Kameda , Taka**** Agari , Taka**** Uozumi , Naoki Tajiri ,
Takamasa Morimoto , Feifei Wang , Meng Jing , Tanefumi Baba , Hanbai
Liang , To****hiro Matsui , Yasuyuki Miyo**** and Isao Date
BMC Neuroscience 2008, 9:75doi:10.1186/1471-2202-9-75
Published: 1 August 2008
Abstract (provisional)
Background
Parkinson's disease (PD) is a neurological disorder characterized by
the degeneration of nigrostriatal dopaminergic systems.
Free radicals induced by oxidative stress are involved in the
mechanisms of cell death in PD.
This study clarifies the neuroprotective effects of Edaravone
(MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one), which has already been
used for the treatment of cerebral ischemia in Japan, on dopaminergic
neurons using PD model both in vitro and in vivo.
6-hydroxydopamine (6-OHDA), a neurotoxin for dopaminergic neurons, was
added to cultured dopaminergic neurons derived from murine embryonal
ventral mesencephalon with subsequet administration of edaravone or
saline.
The number of surviving dopaminergic neurons and the degree of cell
damage induced by free radicals were analyzed.
In parallel, edaravone or saline was intravenously administered for PD
model of rats receiving intrastriatal 6-OHDA lesion with subsequent
behavioral and histological analyses.
Results
In vitro study showed that edaravone significantly ameliorated the
survival of dopaminergic neurons in a dose-responsive manner.
The number of apoptotic cells and HEt-positive cells significantly
decreased, thus indicating that the neuroprotective effects of
edaravone might be mediated by anti-apoptotic effects through the
suppression of free radicals by edaravone.
In vivo study demonstrated that edaravone-administration at 30 minutes
after 6-OHDA lesion reduced the number of amphetamine-induced
rotations significantly in a dose-responsive manner than edaravone-
administration at 24 hours.
Tyrosine hydroxylase (TH) staining of the striatum and substantia
nigra pars compacta revealed that edaravone might exert
neuroprotective effects on nigrostriatal dopaminergic systems.
The neuroprotective effects were prominent when edaravone was
administered early and in high concentration.
Furthermore, Iba-1 staining revealed that the inflammation was
suppressed in rats receiving edaravone-administration.
Conclusions
Edaravone exerts neuroprotective effects on PD model both in vitro and
in vivo through the anti-apoptotic effects via the suppression of free
radicals with subsequent anti-inflammatory effects.
Edaravone might be a safe and hopeful therapeutic option for PD.
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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, im****tant advances have been made to sup****t 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)),
Mitsubi**** Tanabe Pharma Cor****ation) 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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