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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The involvement of oxygen radical species has been implicated in ischemic and post-ischemic brain cell damage. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one; M.W. 174.20, MCI-186, Radicut Injection) has an inhibitory effect on lipid peroxidation by scavenging free radicals and prevents vascular endothelial cell injury. In rat brain ischemic models, post-ischemic treatment with edaravone reduces .OH production and infarction of the ischemic penumbral area and suppresses delayed neuronal death. It also improves neurological deficits and diminishes deterioration of brain edema observed after ischemia. We investigated the efficacy and safety of edaravone in acute ischemic stroke patients. Edaravone improved the core neurological deficits, impaired activities of daily living, and disability, without serious safety problems. Edaravone was approved in Japan for the treatment of acute brain infarction within 24 h after onset in April, 2001. We hope that edaravone represents a promising neuroprotective agent that can contribute to the treatment of acute ischemic stroke.
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PMID:[Pharmacological and clinical profile of the free radical scavenger edaravone as a neuroprotective agent]. 1206 Nov 42

This study investigated the effects of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, MCI-186), a potent free radical scavenger, on the prevention of mitochondrial injury induced by hepatic ischemia and reperfusion. Mature male rats were subjected to 70 min of hepatic ischemia and 2 h of reperfusion. The rats received vehicle or edaravone (10 mg/kg body weight) intravenously prior to ischemia, before reperfusion and 1 h after reperfusion. In the vehicle-treated animals, the respiratory control index, ADP/O, State 3 respiration and dinitrophenol-induced uncoupled respiration decreased markedly after ischemia/reperfusion and were restored by edaravone administration. Mitochondrial lipid peroxidation was elevated in the vehicle-treated group, which was attenuated by edaravone, while mitochondrial glutathione peroxidase activity decreased in the vehicle-treated group, which was similarly abrogated by edaravone treatment. Electron microscopic observation demonstrated that treatment with edaravone restored the ischemia/reperfusion-induced disorganization of mitochondrial structures. Edaravone protects against mitochondrial injury, which prevents mitochondrial oxidative stress and improves ischemia/reperfusion-induced hepatic energy metabolism.
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PMID:Edaravone protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat liver. 1265 Aug 46

We investigated the protective effects of edaravone, a free radical scavenger, against ischemic damage of inner hair cells (IHCs) in gerbils. Cochlear ischemia was induced in the animals by occluding the vertebral arteries bilaterally for 15 min. Edaravone (1 mg/kg, i.v.) or saline was administered 1 h after ischemia. Hearing was assessed by auditory brain response (ABR). In animals treated with saline, the ABR threshold shift was 24.1 dB and there was a 26.5% decrease in the number of IHCs. By contrast, in animals treated with edaravone, the threshold shift was 7.5 dB and only 8.8% of IHCs was lost. These results suggest that edaravone protects against damage to the inner ear following transient ischemia.
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PMID:Free radical scavenger protects against inner hair cell loss after cochlear ischemia. 1453 40

The effects of ozagrel (CAS 82571-53-7), a thromboxane A2-synthetase inhibitor, and norphenazone (CAS 89-25-8), a free-radical scavenger, on cerebral infarction were assessed using the suture-induced middle cerebral artery occlusion (MCAO) model and a microthrombosis model. In the former model, the middle cerebral artery was occluded for 2 h, and the infarction area and volume were evaluated 24 h after the start of reperfusion. In the latter model, microthrombosis were induced by two injections of sodium laurate (interval, 2 days) into the internal carotid artery, and the neurologic deficits were evaluated on the day afer the 2nd injection. Ozagrel at 3 mg/kg decreased both the area and volume of the cortical infarction after ischemia-reperfusion of the middle cerebral artery. Ozagrel also had suppressive effects on the neurologic deficits in the microthrombosis model. Norphenazone at 1 and 3 mg/kg had no clear effects in either model. Since the suture-induced MCAO model and the microthrombosis model are models for occlusion-reperfusion of the major cerebral arteries and lacunar infarction, respectively, these results suggest a highly beneficial effect of ozagrel in the clinical therapy for stroke.
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PMID:Effect of ozagrel, a selective thromboxane A2-synthetase inhibitor, on cerebral infarction in rats. Comparative study with norphenazone, a free-radical scavenger. 1465 Mar 60

Although edaravone (3-methyl-1-phenyl-pyrazolin-5-one), a newly developed radical scavenging agent, has been widely used for protection against ischemia-reperfusion (I-R) injury in patients with cerebral infarction, its effects on gastrointestinal I-R injury have not been evaluated. In the present study, we examined the effects of edaravone on experimental intestinal I-R damage in rats. In male Wistar rats with and without edaravone treatment, intestinal damage was induced by clamping the superior mesenteric artery for 30 min, followed by reperfusion. Edaravone was administered via intravenous infusion at 5 min before reperfusion was achieved by removal of the clamp. The rats were sacrificed after 60 min of reperfusion. Luminal protein and hemoglobin concentrations were measured as an index of mucosal injury and histological examination of hematoxylin and eosin-stained sections was performed. Thiobarbituric acid (TBA)-reactive substances and tissue-associated myeloperoxidase (MPO) activity were measured in the mucosa as indicators of lipid peroxidation and neutrophil infiltration, respectively. The mucosal concentration of cytokine-induced neutrophil chemoattractant (CINC)-1 (a member of the IL-8 family) was determined by enzyme-linked immunosorbent assay (ELISA). Additionally, CINC-1 messenger RNA (mRNA) was measured by the reverse-transcription polymerase chain reaction (RT-PCR). As a result, the levels of luminal protein and hemoglobin, TBA-reactive substances, and MPO activity were all increased significantly by I-R injury, and these increases were significantly inhibited by treatment with edaravone. Multiple erosions and bleeding were observed macroscopically after the small intestine was exposed to I-R injury, and these changes were inhibited by administration of edaravone. Microscopic I-R damage was also reduced by treatment with edaravone. CINC-1 protein and CINC-1 mRNA were both increased by I-R injury, while edaravone markedly reduced the levels of both protein and mRNA. In summary, these results suggest that edaravone can protect the small intestine against I-R injury by scavenging oxygen-derived free radicals.
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PMID:Edaravone, a newly developed radical scavenger, protects against ischemia-reperfusion injury of the small intestine in rats. 1465 79

Edaravone, a novel free radical scavenger, has been reported to reduce ischemic damage in rats subjected to transient focal ischemia. The aim of this study is, therefore, to investigate the effect of a combined therapy with edaravone and mild hypothermia of 35 degrees C. Sprague-Dawley rats were subjected to MCA occluding an intraluminal suture technique for 2 hrs. The rats were reperfused for 24 h and decapitated for infarct and edema analysis. Animals were randomly devided into four groups: (I) vehicle + normothermia (control) (II) vehicle + mild hypothermia (III) Edaravone + normothermia (IV) Edaravone + mild hypothermia. Mild hypothermia alone had no reduction of the brain damage. The edaravone alone significantly reduced edema volume. The combined treatment with edaravone and mild hypothermia reduced both infarct and edema volume. In addition, this treatment provided for the best functional outcome. These results demonstrate that free radical scavenger, edaravone attenuates brain edema and that the combined therapy with edaravone and mild hypothermia significantly reduces not only edema but also infarct on transient focal cerebral ischemia in rats. The neuroprotective effects seen in this study may be due to the combined interaction of antiedema activity between edaravone and mild hypothermia, suppressing free radical production.
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PMID:The neuroprotective effect of a free radical scavenger and mild hypothermia following transient focal ischemia in rats. 1475 35

Increasing data suggest that oxygen free radical species play detrimental roles in ischemic diseases. A free radical scavenger capable of inhibiting oxidative injury is expected to become a new drug for the treatment of ischemic diseases such as cerebral ischemia. Edaravon (3-methyl-1-phenyl-2-pyrazolin-5-one), which has been developed as an neuroprotective agent for more than 15 years since its discovery, is approved for the treatment of acute cerebral infarction. In this paper, the pharmacologic characteristics and clinical effects of edaravone are reviewed. In early stage of investigation, edaravone was found to have promising activities as an antioxidative radical scavenger, quenching hydroxyl radical (.OH) and inhibiting both .OH-dependent and .OH-independent lipid peroxidation. Edaravone showed inhibitory effects on both water-soluble and lipid-soluble peroxyl radical-induced peroxidation systems, which are different from the inhibitory effects of vitamins C and E in each system, respectively. Oxidative injury to cultured endothelial cells caused by arachidonate (AA) peroxides is prevented in the existence of edaravone. To clarify the characteristics of this free radical scavenger, further investigation was carried out. Edaravone ameliorated exacerbation of cortical edema induced by a focal ischemia-reperfusion model in rats, suggesting inhibitory effects on oxidative injury to the blood-brain barrier (BBB). Additionally, edaravone also prevented rat cortical edema caused by intracortical AA infusion in which free radical production and subsequent oxidative injury to the BBB are involved. With advances in in vivo measurement technology of oxygen radicals, edaravone was shown to inhibit postischemic increases in .OH production and tissue injury in the penumbral or recirculated area in rat cerebral ischemia models. In clinical studies, edaravone improved the core neurologic deficits, activities of daily living, and functional outcome of stroke patients. Furthermore, a study using proton magnetic resonance spectroscopic techniques showed that edaravone preserved N-acetyl-aspartate in stroke patients, a promising neuronal marker in the brain. Further investigation is essential for a better understanding of free radical-mediated cerebral injury during ischemia followed by recirculation. We hope that edaravone represents a promising neuroprotectant for drug therapy in acute cerebral ischemia.
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PMID:[Research and development of the free radical scavenger edaravone as a neuroprotectant]. 1504 27

1 We examined whether edaravone (Eda), a clinically available radical scavenger, directly protects cardiomyocytes from ischemia/reperfusion (I/R) injury, and whether the timing of its application is critical for protection. 2 Cardioprotective effects of edaravone were tested in the modified cell-pelleting model of ischemia and under exogenous oxidative stress (hydrogen peroxide: H2O2) in isolated adult rabbit ventricular cells. Cell death and reactive oxygen species (ROS) generation were detected using propidium iodide (PI) and DCFH-DA, respectively. These parameters were evaluated objectively using flow cytometory. 3 Hypoxia and reoxygenation aggravated the proportion of dead cells from 32.2+/-1.8% (Baseline) to 51.3+/-2.7% (Control). When 15 microm edaravone was applied either throughout the entire experiment (Through) or only at reoxygenation (Reox), cell death was significantly reduced to 39.9+/-1.8% (P<0.01 vs Control) and 43.3+/-2.5% (P<0.05 vs Control), respectively. In contrast, when edaravone was applied 10 min after reoxygenation, its protective effect disappeared. Cardioprotection by edaravone was more remarkable than that afforded by other free radical scavengers, such as ascorbate and superoxide dismutase (SOD). There is a positive correlation between the cardioprotective effect of edaravone and the extent of ROS reduction. 4 Edaravone blunted the H2O2-induced changes in electrical properties, and significantly prolonged the time to contracture induced by H2O2 in single ventricular myocytes. 5 Taken together, edaravone directly protects cardiomyocytes from I/R injury by attenuating ROS production, even when applied at the time of reoxygenation, suggesting that edaravone could be a potent cardioprotective therapeutic agent against hypoxia-reoxygenation injury.
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PMID:Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit cardiomyocytes. 1514 65

Ischemia-reperfusion injury causes oxidative stress producing reactive oxygen species, which is a serious problem linked to morbidity and mortality in liver surgery. We investigated the effects of edaravone, a new free radical scavenger, on liver oxidative stress in vitro and in vivo. We employed a hypoxia-reoxygenation model of primary cultured hepatocytes using an AnaeroPack (Mitsubishi Gas Chemical Co., Tokyo, Japan). Hepatocytes were exposed to 3 or 4 hours of hypoxia and then returned to oxygenation. We analyzed the time course changes of aspartate aminotransferase (AST), phosphatidylcholine hydroperoxide (PCOOH), and adenosine triphosphate (ATP) content in hepatocytes of edaravone-treated groups or nontreated groups after reoxygenation. Edaravone significantly attenuated the elevation of the AST level of the medium and hepatocellular PCOOH and preserved the hepatocellular ATP level. In vivo, male Sprague-Dawley rats were subjected to 45 minutes of hepatic ischemia and 120 minutes of reperfusion. The rats were intravenously injected with vehicle or edaravone (3 mg/kg or 10 mg/kg) before reperfusion and 1 hour after reperfusion. Serum AST levels and hepatic PCOOH and energy charge were significantly improved in both edaravone groups compared with control. In conclusion, edaravone has the ability to eliminate intra-hepatocellular superoxide species and attenuate oxidative liver damage in liver surgery.
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PMID:A new free radical scavenger, edaravone, ameliorates oxidative liver damage due to ischemia-reperfusion in vitro and in vivo. 1523 99

The present study was aimed to evaluate the effect of the free radical scavenger Edaravone on infarct volume due to permanent MCA occlusion in mice and, if so, to elucidate the mechanism of its neuroprotective effects. Male Balb/c mice were subjected to permanent middle cerebral artery occlusion and were treated with 3.0 mg/kg of Edaravone or vehicle 30 min before ischemia. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) method after 24 h. Furthermore, in situ detection of superoxide in the ipsilateral neocortex was carried out using the superoxide-sensitive dye dihydroethidium (DHE) staining technique. Pretreatment with 3.0 mg/kg of Edaravone ameliorated the tissue damage in the infarct rim and significantly reduced infarct volume to about 77% of the control (p<0.05). Semi-quantitative measurement of red fluorescence emitted from DHE revealed that the superoxide increased in the ischemic core at 1 h after the onset of ischemia and extended towards the infarct rim at 3 and 6 h, and that pretreatment with 3.0 mg/kg of Edaravone significantly inhibited the increase of superoxide in the infarct rim at 3 and 6 h (p<0.01). Double staining with DHE and monoclonal antibody against NeuN showed that the majority of the nuclei positive for DHE were also positive for NeuN. These findings suggest that Edaravone salvages the boundary zone of infarct by scavenging reactive oxygen species especially in the neurons during permanent focal cerebral ischemia.
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PMID:Neuroprotective effects of the free radical scavenger Edaravone (MCI-186) in mice permanent focal brain ischemia. 1554 75


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