Preventive effect of MCI-186 on 15-HPETE induced vascular endothelial cell injury in vitro

Watanabe, Toshiaki; Morita, I.; Nishi, Hideyuki; Murota, Sie-Itsu

doi:10.1016/0952-3278(88)90127-5

Cited by 164 publications

(108 citation statements)

References 15 publications

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“…These results are consistent with previously published reports (Dohi et al, 2006(Dohi et al, , 2007. It has been reported that edaravone inhibits both nonenzymatic lipid peroxidation and the lipoxygenase pathway (Watanabe et al, 1988), and it has potent antioxidant effects against ischemia and reperfusion-induced vascular endothelial cell injury, delayed neuronal death, brain edema, and concomitant neurological deficits (Yoshida et al, 2006). The majority of these findings were reproduced in the current study.…”

Section: Fig 3 Inhibition Of Astrocyte Activation By Edaravone (A)supporting

confidence: 83%

“…Total oxidative stress under vehicle-treated conditions may thus overestimate lipid peroxidation because of oxidative stress. Edaravone, however, is known to block both the formation of free radicals and the conversion of arachidonic acid by inhibiting lipoxygenase (Watanabe et al, 1988). The reduction of MDA in edaravone-treated rats is caused by inhibition of both pathways, and our results indicate that edaravone treatment decreased MDA production to shamtreated levels (Table 1).…”

Section: Fig 3 Inhibition Of Astrocyte Activation By Edaravone (A)supporting

confidence: 64%

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Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

Wang

Zheng

Li³

et al. 2011

Journal of Neurotrauma

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Traumatic brain injury (TBI) is one of the leading causes of neurological disability in young adults. Edaravone, a novel synthetic small-molecule free-radical scavenger, has been shown to have a neuroprotective effect in both animal models of cerebral ischemia and stroke patients; however, the underlying mechanism is poorly understood. In this report, we investigated the potential mechanisms of edaravone treatment in a rat model of TBI. TBI was induced in the right cerebral cortex of male adult rats using Feeney's weight-drop method. Edaravone (0.75, 1.5, or 3 mg/kg) or vehicle (normal saline) was intravenously administered at 2 and 12 h after TBI. Edaravone treatment significantly decreased hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal programmed cell death compared to vehicle treatment. The protective effects of edaravone treatment were also related to the pathology of TBI on non-neuronal cells, as edaravone decreased astrocyte and glial activation. Lastly, edaravone treatment significantly reduced the presence of inflammatory cytokines, cerebral edema, blood-brain barrier (BBB) permeability, and, importantly, neurological deficits following TBI. Our results suggest that edaravone exerts a neuroprotective effect in the rat model of TBI. The likely mechanism is via inhibiting oxidative stress, leading to a decreased inflammatory response and glial activation, and thereby reducing neuronal death and improving neurological function.

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Section: Fig 3 Inhibition Of Astrocyte Activation By Edaravone (A)supporting

confidence: 83%

Section: Fig 3 Inhibition Of Astrocyte Activation By Edaravone (A)supporting

confidence: 64%

Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

Wang

Zheng

Li³

et al. 2011

Journal of Neurotrauma

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“…Edaravone is reported to prevent lipid peroxidation by scavenging free radicals produced during brain ischemia, which offers protection against ischemic and postischemic brain damage. [15][16][17] Pressure overload-induced hypertrophy was introduced with the transverse thoracic aorta constriction (TAC) technique. This model is widely used in the study of mice to identify molecular mechanisms for cardiac hypertrophy.…”

mentioning

confidence: 99%

The Antioxidant Edaravone Attenuates Pressure Overload–Induced Left Ventricular Hypertrophy

Tsujimoto

Hikoso²,

Yamaguchi³

et al. 2005

Hypertension

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Abstract-The free radical scavenger 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone) is used to treat patients with ischemic brain damage. We and others reported previously that in vitro and in vivo reactive oxygen species (ROS) act as second messengers to develop cardiac hypertrophy. In this study, we used an in vivo murine model of pressure overload-induced cardiac hypertrophy to examine the effects of edaravone on left ventricular hypertrophy. The animals were subjected to the transverse thoracic aorta constriction, and edaravone (10 mg/kg) was infused intraperitoneally twice daily. Seven days after the operation, we observed a significant increase in ROS production in hearts, which was eliminated by the treatment with edaravone. Pressure-overloaded hearts showed a significant increase in left ventricular weight/body weight ratio and the expression level of atrial natriuretic factor mRNA, which were attenuated by edaravone. It also reduced perivascular and intermuscular fibrosis and inhibited pressure overload-induced activation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream kinases of c-Jun N-terminal protein kinase and p38 mitogen-activated protein kinase. Edaravone attenuated the hypertrophic response even when the treatment was started after the onset of cardiac hypertrophic response. These findings indicate that edaravone significantly attenuates pressure overload-induced cardiac hypertrophy mediated through its antioxidative function and subsequent inhibition of ASK1 signaling pathway.

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“…Previous in vitro studies have suggested that edaravone will protect the vascular endothelial cells in the ischemic lesion, 22) and reduce hemorrhagic transformation. 24) However, the present study showed that the frequency of hemorrhagic transformation increased in patients with cardiogenic embolism who M. Mishina et al…”

Section: Discussionmentioning

confidence: 99%

“…1) Edaravone was apparently efficacious in patients with acute ischemic stroke, 7,14) and protected vascular endothelial cells and neurons during acute brain ischemia. 22) EPC-K1, another free radical scavenger, combined with heparin dramatically reduced heparin-induced hemor- Fig. 1 Mechanisms of free radicals affecting the pathways of coagulation and thrombolysis.…”

Section: Introductionmentioning

confidence: 99%

Administration of Free Radical Scavenger Edaravone Associated With Higher Frequency of Hemorrhagic Transformation in Patients With Cardiogenic Embolism

Mishina

Komaba

Kobayashi

et al. 2008

Neurol. Med. Chir.(Tokyo)

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Free radicals are known to activate coagulation and inhibit fibrinolysis. Edaravone, a free radical scavenger, protects vascular endothelial cells and neurons during acute brain ischemia in in vitro models. Hemorrhagic transformation and treatment outcomes were retrospectively examined in 76 patients with acute cardiogenic embolism treated with edaravone in addition to routine treatment within 24 hours of the onset of symptoms. Hemorrhagic transformation was categorized according to European Cooperative Acute Stroke Study-II. Patient characteristics were also evaluated, including evidence of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, history of smoking, National Institutes of Health Stroke Scale on arrival, and modified Rankin scale at 3 months postonset. Edaravone administration was one of the factors that contributed to increased frequency of hemorrhagic transformation, but had showed no significant relationship with the outcome. The present study showed that edaravone administration increased the frequency of hemorrhagic transformation with heparin in patients with cardiogenic embolism. Free radical scavenging may have promoted the coagulating conditions. Edaravone administration may allow reduction of the dose of heparin and tissue plasminogen activator in patients with acute ischemic stroke.

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Preventive effect of MCI-186 on 15-HPETE induced vascular endothelial cell injury in vitro

Cited by 164 publications

References 15 publications

Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

The Antioxidant Edaravone Attenuates Pressure Overload–Induced Left Ventricular Hypertrophy

Administration of Free Radical Scavenger Edaravone Associated With Higher Frequency of Hemorrhagic Transformation in Patients With Cardiogenic Embolism

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