Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemiareperfusion injury in rats<sup>1</sup>

Song, Yi; Gong, Yuanyuan; Xie, Zijian; Li, Caihong; Gu, Qing; Wu, Xinming

doi:10.1111/j.1745-7254.2008.00822.x

Cited by 30 publications

(18 citation statements)

References 27 publications

(29 reference statements)

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“…In ischemic stroke models, it may improve neurologic function by decreasing oxidative DNA damage and brain edema (Niyaz et al, 2007;Song et al, 2008). A recent study found that MCI-186 could protect neural stem cells from irradiation and restore their differentiation in human (Ishii et al, 2007).…”

Section: Discussionmentioning

confidence: 97%

Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Shen

Xin-sheng

et al. 2012

Neuroscience

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Section: Discussionmentioning

confidence: 97%

Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Shen

Xin-sheng

et al. 2012

Neuroscience

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“…[15][16][17][18] Interestingly, edaravone attenuates retinal ischemia/reperfusion injury in rats 19 and retinal damage in experimental rats with glaucoma showing high intraocular pressure. 20 These findings suggest a possibility that edaravone protects RGCs by scavenging reactive oxygen species (ROS).…”

Section: -11mentioning

confidence: 99%

Edaravone Prevents Retinal Degeneration in Adult Mice Following Optic Nerve Injury

Akiyama

Azuchi

Guo

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To assess the therapeutic potential of edaravone, a free radical scavenger that is used for the treatment of acute brain infarction and amyotrophic lateral sclerosis, in a mouse model of optic nerve injury (ONI).METHODS. Two microliters of edaravone (7.2 mM) or vehicle were injected intraocularly 3 minutes after ONI. Optical coherence tomography, retrograde labeling of retinal ganglion cells (RGCs), histopathology, and immunohistochemical analyses of phosphorylated apoptosis signal-regulating kinase-1 (ASK1) and p38 mitogen-activated protein kinase (MAPK) in the retina were performed after ONI. Reactive oxygen species (ROS) levels were assessed with a CellROX Green Reagent.RESULTS. Edaravone ameliorated ONI-induced ROS production, RGC death, and inner retinal degeneration. Also, activation of the ASK1-p38 MAPK pathway that induces RGC death following ONI was suppressed with edaravone treatment. CONCLUSIONS.The results of this study suggest that intraocular administration of edaravone may be a useful treatment for posttraumatic complications.Keywords: edaravone, oxidative stress, neuroprotection, ASK1, retinal ganglion cell T raumatic optic neuropathy is a common clinical problem that occurs in 0.5% to 5% of patients with closed head injury.1 Damage to the optic nerve induces secondary swelling within the optic canal, accompanied by subsequent retinal ganglion cell (RGC) loss and optic nerve atrophy.2 Although no large natural history or randomized controlled trials have been published, corticosteroid therapy and optic canal decompression surgery are not considered to be effective for patients with traumatic optic neuropathy.3 Research into finding therapeutic targets for treatment of traumatic optic neuropathy indicated that neuroprotection might be an effective strategy and studies using an optic nerve injury (ONI) model in rodents have provided useful information. For example, neurotrophins, such as brain-derived neurotrophic factor and ciliary neurotrophic factor, protect retinal RGCs in an ONI model. [4][5][6] Also, inhibitors of glutamate receptors, tumor necrosis factor receptors, and nitric oxide synthase may be effective for RGC protection. 7-11The ONI model mimics some aspects of glaucoma, including RGC death induced by oxidative stress, and therefore, it is also a useful animal model for glaucoma.Edaravone is a free radical scavenger that has been used clinically to treat acute brain infarction and amyotrophic lateral sclerosis (ALS). Edaravone quenches hydroxyl radicals ( Á OH) and inhibits lipid peroxidation dependent and independent of Á OH. 12,13 In an in vitro cell culture study using the RGC-5 to study the neurobiology of RGCs, edaravone scavenged the intracellular Á OH, superoxide anion (O 2 ÀÁ ), and hydrogen peroxide (H 2 O 2 ) while demonstrating the strongest scavenging activity against14 Recent studies have shown that oxidative stress plays an important role in many ocular diseases including glaucoma. [15][16][17][18] Interestingly, edaravone attenuates retinal ischemia/reperfusion ...

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“…These protective effects of edaravone are thought to be attributable to its scavenging of ROS. More recently, Song et al (2008) reported that systemic administration of edaravone attenuated the increase of malondialdehyde levels, the reduction of superoxide dismutase activity, and furthermore suppressed the retinal dysfunctions after retinal ischemia/reperfusion in rats (Song et al, 2008). However, they did not determine any quantitative evaluation in RGC death after retinal injury; so, it remains unclear whether edaravone protects against RGC death with apoptosis through ROS-scavenging effects.…”

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confidence: 99%

Edaravone, a Free Radical Scavenger, Protects against Retinal Damage in Vitro and in Vivo

Inokuchi¹,

Imai²,

Nakajima³

et al. 2009

J Pharmacol Exp Ther

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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 ( ⅐ 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 mitogenactivated protein kinases (MAPKs) [extracellular signalregulated 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 TUNELpositive 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.

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Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemiareperfusion injury in rats¹

Cited by 30 publications

References 27 publications

Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Edaravone Prevents Retinal Degeneration in Adult Mice Following Optic Nerve Injury

Edaravone, a Free Radical Scavenger, Protects against Retinal Damage in Vitro and in Vivo

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Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemiareperfusion injury in rats1

Cited by 30 publications

References 27 publications

Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Protective effects of MCI-186 on transplantation of bone marrow stromal cells in rat ischemic stroke model

Edaravone Prevents Retinal Degeneration in Adult Mice Following Optic Nerve Injury

Edaravone, a Free Radical Scavenger, Protects against Retinal Damage in Vitro and in Vivo

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Edaravone (MCI-186), a free radical scavenger, attenuates retinal ischemiareperfusion injury in rats¹