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edaravone inhibits apoptosis caused by ischemia/reperfusion injury in a porcine hepatectomy model

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World Journal of Gastroenterology 2012年第27期18卷 3520-3526页

作者： Mitsugi Shimoda Yoshimi Iwasaki Toshie Okada Keiichi Kubota Second Department of Surgery Dokkyo Medical University880 Kita KobayashiMibuTochigi 321-0293Japan

AIM： TO investigate the effect of E3-methyl-l-phe- nyl-2-pyrazolin-5-one （Edr） on hepatic ischemia-reper- fusion （I/R） injury and liver regeneration in a porcine hepatectomy model. METHODS： One hour ischemia was induced by occlud- ing the vessels and the bile duct of the right and median lobes. A 40% left hepatectomy was performed after re- perfusion. Six animals received Edr （3 mg/kg per hour） intravenously and six control animals received saline just before reperfusion. Remnant liver volume, hemody- namics, aspartate aminotransferase （AST）, alanine ami- notransferase, lactate dehydrogenase and lactic acid, were compared between the groups. The expression of transforming growth factor-β （TGF-β1） and toll-like receptor （TRL） mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction. Apoptosis was demonstrated by terminal deoxynucleo- tidyl transferase dUTP nick end labeling （TUNEL） stain- ing, respectively. RESULTS： Serum AS-I- （P = 0.029）, and toll like recep- tor 4 level （P = 0.043） were significantly lower after 3 hin animals receiving Edr. In addition, TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs. After 1 mo, all factors were non-significantly different between the two groups. CONCLUSION： Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.

关键词： edaravone Ischemia-reperfusion injury Liver resection Transforming growth factor-13 Toll likereceptor 4

edaravone combined with Schwann cell transplantation may repair spinal cord injury in rats

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Neural Regeneration Research 2015年第2期10卷 230-236页

作者： Shu-quan Zhang Min-fei Wu Zhe Piao Jin Yao Ji-hai Li Xin-gang Wang Jun Liu Department of Orthopedics Tianjin Nankai Hospital Department of Spine Surgery Orthopedic Hospital Second Hospital Clinical Hospital Jilin University Department of Burns and Plastic Surgery China-Japan Union Hospital Jilin University Department of Hand and Foot Surgery and Reparative & Reconstructive Surgery Center Orthopedic Hospital Second Hospital Clinical Hospital Jilin University

edaravone has been shown to delay neuronal apoptosis, thereby improving nerve function and the microenvironment after spinal cord injury. edaravone can provide a favorable environment for theAa：eatment of spinal cord injury using Schwann cell transplantation. This study used rat models of complete spinal cord transection at T9. Six hours later, Schwann cells were transplanted in the head and tail ends of the injury site. Simultaneously, edaravone was injected through the caudal vein. Eight weeks later, the PKH-26-1abeled Schwann cells had survived and migrated to the center of the spinal cord injury region in rats after combined treatment with edaravone and Schwann cells. Moreover, the number of PKH-26-1abeled Schwann cells in the rat spinal cord was more than that in rats undergoing Schwann cell transplantation alone or rats without any treatment. Horseradish peroxidase retrograde tracing revealed that the number of horserad- ish peroxidase-positive nerve fibers was greater in rats treated with edaravone combined with Schwann cells than in rats with Schwann cell transplantation alone. The results demonstrated that lower extremity motor function and neurophysiological function were better in rats treated with edaravone and Schwann cells than in rats with Schwann cell transplantation only. These data confirmed that Schwann cell transplantation combined with edaravone injection promoted the regeneration of nerve fibers of rats with spinal cord injury and improved neurological function.

关键词： nerve regeneration spinal cord injury Schwann cells cell transplantation edaravone motor function electrophysiological function neural regeneration

Influence of edaravone on Notch1 and nuclear factor-kappaB in rats with cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2008年第12期3卷 1342-1347页

作者： Yonglong Wang Zhiyou Cai Yong Luo Jiaming Gong Department of Neurology First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Neurology Chongqing400016 China

BACKGROUND： It has been demonstrated that edaravone has a a neuroprotective role, inhibits free radical increase, and reduces celt apoptosis. The Notch pathway is a key factor in neurogenesis and cellular apoptosis The proinflammatory transcription factor nuclear factor-kappaB （NF-κB） plays an important role in inflammation and oxidation. OBJECTIVE： To observe the influence of edaravone on Notchl and NF-κB mRNA and protein expression in rats with focal cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： This randomized controlled neural and molecular biology experiment was performed at the Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, and the Chongqing Key Laboratory of Neurology between July 2007 and May 2008. MATERIALS： Thirty female Wistar rats were used. edaravone was purchased from Jiangsu Xiansheng Pharmaceutical Limited Company, China. METHODS： Wistar rats were randomly divided into five groups （n = 6）. Thread was inserted into the internal carotid artery of the sham operation group but the middle cerebral artery was not ligated. A focal cerebral ischemia/reperfusion model was established by inserting thread into the right middle cerebral artery. The model rats in the edaravone groups were given tail vein injections of edaravone at 3 mg/kg body weight after ischemia for 2 hours and reperfusion for 12 or 24 hours. Ischemia/reperfusion groups （model group） received intravenous infusion of normal saline at the same volume as the edaravone groups after ischemia for 2 hours and reperfusion for 12 or 24 hours. MAIN OUTCOME MEASURES： The volume of the ischemic region was measured by 2,3,5-triphenyltetrazolium chloride staining. Notchl and NF-κB protein and mRNA expression were measured by immunohistochemistry and RT-PCR. Protein expression was represented by the absorbance value. RESULTS： edaravone greatly reduced the focal infarct volume. Notchl and NF-κB protein and mRNA expression were rapidly upregulated foll

关键词： cerebral ischemia/reperfusion edaravone Notchl nuclear factor-kappaB

edaravone protects PC12 cells from ischemic-like injury via attenuating the damage to mitochondria

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2006年第9期7卷 749-756页

作者： SONG Ying LI Meng LI Ji-cheng WEI Er-qing Department of Cellular Biology School of Medicine Zhejiang University Hangzhou 310031 China Department of Pharmacology School of Medicine Zhejiang University Hangzhou 310031 China

Background： edaravone had been validated to effectively protect against ischemic injuries. In this study, we investigated the protective effect of edaravone by observing the effects on anti-apoptosis, regulation of Bcl-2/Bax protein expression and recovering from damage to mitochondria after OGD （oxygen-glucose deprivation）-reperfusion. Methods： Viability of PC 12 cells which were injured at different time of OGD injury, was quantified by measuring MTT （2-（4,5-dimethylthia-zol-2-yl）-2,5-diphenyltetrazolium bromide） staining. In addition, PC 12 cells＇ viability was also quantified after their preincubation in different concentration of edaravone for 30 min followed by （OGD）. Furthermore, apoptotic population of PC 12 cells that reinsulted from OGD-reperfusion with or without preincubation with edaravone was determined by flow cytometer analysis, electron microscope and Hoechst/Pl staining. Finally, change of Bcl-2/Bax protein expression was detected by Western blot. Results：（1） The viability of PC12 cells decreased with time （1-12 h） after OGD. We regarded the model of OGD 2 h, then replacing DMEM （Dulbecco＇s Modified Eagle＇s Medium） for another 24 h as an OGD-reperfusion in this research. Furthermore, most PC 12 cells were in the state of apoptosis after OGD-reperfusion. （2） The viability of PC 12 cells preincubated with edaravone at high concentrations （1, 0.1, 0.01 μmol/L） increased significantly with edaravone protecting PC 12 cells from apoptosis after OGD-reperfusion injury. （3） Furthermore, edaravone attenuates the damage of OGD-reperfusion on mitochondria and regulated Bcl-2/Bax protein imbalance expression after OGD-reperfusion. Conclusion： Neuroprotective effects of edaravone on ischemic or other brain injuries may be partly mediated through inhibition of Bcl-2/Bax apoptotic pathways by recovering from the damage of mitochondria.

关键词： edaravone lschemia Apoptosis Rat pheochromocytoma (PC 12) cells Mitochondria Bax Bcl-2 Oxygen-glucose deprivation (OGD)

edaravone administration and its potential association with a new clinical syndrome in cerebral infarction patients:Three case reports

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World Journal of Clinical Cases 2023年第19期11卷 4648-4654页

作者： Liu Yang Xin Xu Liang Wang Ke-Bin Zeng Xue-Feng Wang Department of Neurology Central Hospital Affiliated to Chongqing UniversityChongqing 400010China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND edaravone is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are ***,edaravone-related adverse reactions have been receiving increasing *** SUMMARY We treated three patients with acute cerebral infarction who died following treatment with *** is a widely used treatment for patients with cerebral infarction and,in most cases,edaravone-induced side effects are ***,edaravone-related adverse reactions have been receiving increasing *** Our cases highlight the importance of educating clinicians regarding the new edaravone-induced clinical syndromes of cerebral infarction as potentially fatal adverse drug *** that no laboratory or confirmatory test exists to diagnose edaravone-induced death from cerebral infarction,clinicians’knowledge is the key element in recognizing this phenomenon.

关键词： edaravone Sudden death Patients Cerebral infarction Case report

Neuroprotective role of edaravone and the effects of endoplasmic reticulum stress in an adult rat model of focal cerebral ischemia/reperfusion

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Neural Regeneration Research 2010年第3期5卷 197-204页

作者： Xiangmin Shen Liming Tan Yunhai Liu Hainan Zhang Chunyu Wang Qidong Yang QingHuang Lin Zhou Zhenyu Tang Department of Neurology Xiangya Hospital Central South University Changsha 410008 Hunan Province China Department of Neurology Second Xiangya Hospital Central South University Changsha 410011 Hunan Province China

BACKGROUND： Endoplasmic reticulum （ER） stress impairs ER functions and leads to the accumulation of unfolded or misfolded proteins in the ER lumen. ER stress-induced cell death plays an important role in cerebral ischemia. Edaravon （3-methyl-1-phenyl-2-pyrazolin-5-one） is a potent and novel scavenger of free radicals that inhibit delayed neuronal death, as demonstrated by in vitro and animal studies. However, its effect on ER stress and induced neuronal apoptosis in a rat model of brief middle cerebral artery occlusion remains unclear. OBJECTIVE： To explore the effects of edaravone on the expression of ER stress-related factors and neuronal apoptosis, based on the hypothesis that edaravone influences ER stress in a rat model of cerebral ischemia/reperfusion. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of Department of Neurology, Xiangya Hospital and the Department of Laboratory Animals, Xiangya Medical College, Central South University in China from June 2005 to May 2006. MATERIALS： edaravone was purchased from Simcere Pharmaceutical Group, China. METHODS： A total of 216 adult, male, Sprague Dawley rats were randomly assigned to sham-surgery, model and edaravone groups, with 72 rats in each group, Brief middle cerebral artery occlusion was established in the model and edaravone groups. In addition, the edaravone group rats were injected with 3 mg/kg edaravone through the tail vein. MAIN OUTCOME MEASURES： RNA-dependent protein kinase-like endoplasmic reticulum eukaryotic translation initiation factor 2a kinase （PERK） and C/EBP homology protein （CHOP） mRNA expression in the ischemic parietal cortex was determined by reverse transcriptionpolymerase chain reaction; phosphorylated PERK and CHOP protein expression was detected by immunohistochemistry; neuronal apoptosis was detected by TdT-mediated-dUTP nick end labeling. RESULTS： Neurological deficit scores were significantly reduced in the edaravone group compared to

关键词： edaravone cerebral ischemia/reperfusion endoplasmic reticulum stress RNA-dependent protein kinase-like endoplasmic reticulum elF2a kinase C/EBP homology protein brain injury neural regeneration

Neuroprotective effect of edaravone in experimental glaucoma model in rats: a immunofluorescence and biochemical analysis

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International Journal of Ophthalmology(English edition) 2015年第2期8卷 239-244页

作者： Arzu Toruk Aksar Nursen Yuksel Mustafa Gok Mustafa Cekmen Yusuf Caglar Department of Ophthalmology Kocaeli University Faculty of Medicine Department of Ophthalmology Ministry of Health-Ordu University Research and Training Hospital Department of Biochemistry Kocaeli University Faculty of Medicine

AIM: To evaluate the neuroprotective activity of systemically administered edaravone in early and late stage of experimental glaucoma in ***: In this study, 60 Wistar albino rats were used. Experimental glaucoma model was created by injecting hyaluronic acid to the anterior chamber once a week for 6wk in 46 of 60 subjects. Fourteen subjects without any medication were included as control *** administered intraperitoneally 3 mg/kg/d to the 15 of 30 subjects starting at the onset of glaucoma induction and also administered intraperitoneally3 mg/kg/d to the other 15 subjects starting at three weeks after the onset of glaucoma induction. The other16 subjects who underwent glaucoma induction was administered any therapy. Retinal ganglion cells(RGCs)have been marked with dextran tetramethylrhodamine(DTMR) retrograde at the end of the sixth week and after48 h, subjects were sacrificed by the method of cardiac perfusion. Alive RGC density was assessed in the wholemount retina. Whole-mount retinal tissues homogenized and nitric oxide(NO), malondialdehyde(MDA) and total antioxidant capacity(TAC) values were measured ***: RGCs counted with Image-Pro Plus program, in the treatment group were found to be statistically significantly protected, compared to the glaucoma group(Bonferroni,P edaravone was found to be more influential byadministration at the start of the glaucoma *** significant lower NO levels were determined in the glaucoma group comparing treatment groups(Bonferroni, P edaravone in experimental glaucoma showed potent neuroprotective activity. The role of oxidative stress causing RGC damage in glaucoma was supported by this study results.

关键词： antioxidant edaravone glaucoma neuroprotection

Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction

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World Journal of Psychiatry 2024年第5期14卷 644-652页

作者： Tian-Shu Wang Li-Jun Jing Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Cerebral infarction(CI)is characterized by a high prevalence,disability,and *** or improper treatment greatly affects patient *** To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life(QOL),anxiety and depression in CI *** We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group(OG)(combination therapy of aspirin and edaravone,65 patients)or a control group(CG)(aspirin monotherapy,59 patients).The therapeutic effects,pre-and posttreatment National Institutes of Health Stroke Scale(NIHSS)scores,activities of daily living,degree of cognitive impairment,protein levels of glial fibrillary acidic protein(GFAP),neuron-specific enolase(NSE)and S-100B,occurrence of adverse reactions,and serum high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere evaluated,detected and compared between the two ***,posttreatment QOL,anxiety,and depression were assessed by the Medical Outcomes Study 36-Item Short Form Health Survey Scale,Self-rating Depression Scale(SDS),and Self-rating Anxiety Scale(SAS),*** Compared with the CG,the OG had markedly better therapeutic effects,greater improvements in activities of daily living,and better alleviation in cognitive dysfunction after treatment,as well as lower posttreatment NIHSS scores and serum NSE,GFAP,S-100B,hs-CRP,IL-6,and TNF-αlevels;the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL;and the OG also had lower SDS and SAS scores than the CG after *** Aspirin plus edaravone had a good curative effect on *** can reverse cranial nerve damage in patients,improve neurological function and prognosis,and alleviate inflammation,anxiety,and depression;thus,it is considered safe and worthy of clinical application.

关键词： Aspirin edaravone Cerebral infarction Efficacy Quality of life

edaravone attenuates ischemia-reperfusion injury by inhibiting oxidative stress in a canine lung transplantation model

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Chinese Medical Journal 2008年第16期121卷 1583-1587页

作者： XU Jin-zhi SHEN Bao-zhong LI Ye ZHANG Tong XU Wan-hai LIU Xiao-wei LU Hong-guang Department of Thoracic Surgery Fourth Affiliated Hospital of Harbin Medical University Harbin Heilongjiang 150001 China Department of Medical Imaging Fourth Affiliated Hospital of Harbin Medical University Harbin Heilongjiang 150001 China

Background Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion （IR） injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model. Methods Twelve weight-matched pairs of random-bred dogs were randomized into two groups. Within each pair, one dog served as donor and the other as recipient. In the study group, prostaglandin EI（PGE1）（8 μg/kg） was injected into the donor pulmonary artery （PA） before occlusion and the donor lungs were flushed with 1.0 L of LPD solution containing edaravone （10 mg/kg） and stored in the same LPD solution at a temperature of 1℃for 8 hours. The left single lung transplantation was then performed and recipients received intravenous injection with edaravone （10 mg/kg） at the onset of reperfusion. In the control group, edaravone was substituted by the same volume of sterile saline solution. Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury. One hour after reperfusion, or after dissection of the left lung, the right lung was excluded from perfusion and ventilation after which, cardiopulmonary parameters were measured. Wet/dry ratios, malondialdehyde （MDA） and myeloperoxidase （MPO） levels were assessed and histological analysis of lung tissue performed at the same time. Results All animals survived until the end of the experiment. The study group showed significantly decreased wet/dry ratios （treated：（74.1±4.2）% vs control：（86.8±5.2）%, P 〈0.01）, MDA levels （treated： 0.50±0.08 vs control： 0.88±0.15, P 〈0.01） and MPO activity （treated： 0.23±0.05 vs control： 0.43±0.07, P 〈0.01） compared to the control group two hours after occlusion of the right side. In the control group, pulmonary vascular resistance （PVR） was increased markedly and arterial oxygen partial pressure deteriorated significantly after exclusion of the right side compare

关键词： edaravone ischemia-reperfusion injury lung transplantation oxidative stress reactive oxygen species