Edaravone's free radical scavenging mechanisms of neuroprotection against cerebral ischemia: review of the literature

References

• Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet 2013;380(9859):2095–28.
   Web of Science ®Google Scholar
• Eugene SF, Demopoulos HB, Seligman ML, et al. Free radicals in cerebral ischemia. Stroke 1987;9(5):445–47.
   Google Scholar
• Alexandrova ML, Bochev PG. Oxidative stress during the chronic phase after stroke. Free Radic Biol Med 2005;39(3):297–316.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Yuki S, Egawa M, Nishi H. Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions. J Pharmacol Exp Ther. 1994;268(3):1597–1604.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Egawa M. Effects of an antistroke agent MCI-186 on cerebral arachidonate cascade. J Pharmacol Exp Ther 1994;271(3):1624–29.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Tahara M, Todo S. The novel antioxidant edaravone: from bench to bedside. Cardiovasc Ther 2008;26(2):101–14.
   PubMed Web of Science ®Google Scholar
• Lapchak PA. A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy? Expert Opin Pharmacother 2010;11(10):1753–63.
   PubMed Web of Science ®Google Scholar
• Yoshida H, Mimura J, Imaizumi T, et al. Edaravone and carnosic acid synergistically enhance the expression of nerve growth factor in human astrocytesunder hypoxia/reoxygenation. Neurosci Res 2011;69(4):291–98.
   PubMed Web of Science ®Google Scholar
• Yoshida H, Metoki N, Ishikawa A, et al. Edaravone improves the expression of nerve growth factor in human astrocytes subjected to hypoxia/reoxygenation. Neurosci Res 2010;66(3):284–89.
   PubMed Web of Science ®Google Scholar
• Yamamoto Y, Yanagisawa M, Tak NW, et al. Repeated edaravone treatment reduces oxidative cell damage in rat brain induced by middle cerebral artery occlusion. Redox Rep 2009;14(6):251–58.
   PubMed Web of Science ®Google Scholar
• Toyoda K, Fujii K, Kamouchi M, et al. Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion. J Neurol Sci 2004;221(1–2):11–17.
   PubMed Web of Science ®Google Scholar
• Amemiya S, Kamiya T, Nito C, et al. Anti-apoptotic and neuroprotective effects of edaravone following transient focal ischemia in rats. Eur J Pharmacol 2005;516(2):125–30.
   PubMed Web of Science ®Google Scholar
• Charanjit K, Eng-Ang L. Antioxidants and neuroprotection in the adult and developing central nervous system. Curr Med Chem 2008;15(29):3068–80.
   PubMed Web of Science ®Google Scholar
• Erisa K, Yoshimi S. A multiple free-radical scavenging (MULTIS) study on the antioxidant capacity of a neuroprotective drug, edaravone as compared with uric acid, glutathione, and trolox. Bioorg Med Chem Lett 2014;24(5):1376–79.
   PubMed Web of Science ®Google Scholar
• Romanos E, Planas AM, Amaro S, Chamorro A. Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab Jan 2007;27(1):14–20.
   PubMed Web of Science ®Google Scholar
• Miedema I, Uyttenboogaart M, Koch M, et al. Lack of association between serum uric acid levels and outcome in acute ischemic stroke. J Neurol Sci 2012;319(1–2):51–55.
   PubMed Web of Science ®Google Scholar
• Hongliang W, Qian J, Gaifen L, et al. Decreased uric acid levels correlate with poor outcomes in acute ischemic stroke patients, but not in cerebral hemorrhage patients. J Stroke Cerebrovasc Dis. 2014;23(3):469–75.
   PubMed Web of Science ®Google Scholar
• Jiangyong M, Muhammad UF, Philip BG. Neuroprotective agents in ischemic stroke: past failures and future opportunities. Clin Invest 2013;3(12):1167–77.
   Google Scholar
• Michalis P, Simon N, Alastair M B. Development and efficacy of NXY-059 for the treatment of acute ischemic stroke. Future Neurology 2008;3(3):229–40.
   Google Scholar
• Kennedy RL, Justin AZ, Tim A, et al. NXY-059 for acute ischemic stroke. N Engl J Med 2007;357(6):562–71.
   PubMed Web of Science ®Google Scholar
• Yukito S, Sachie I. Cost-effectiveness analysis of the neuroprotective agent edaravone for noncardioembolic cerebral infarction. J Stroke Cerebrovasc Dis 2013;22(5):668–74.
   PubMed Web of Science ®Google Scholar
• Saito A, Maier CM, Narasimhan P, et al. Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol Neurobiol 2005;31(1–2):105–16.
   PubMed Web of Science ®Google Scholar
• Brieger K, Schiavone S, Miller Fj, Jr, Krause KH. Reactive oxygen species: from health to disease. Swiss Med Wkly 2012;142:w13659.1–14.
   Google Scholar
• Shichinohe H, Kuroda S, Yasuda H, et al. Neuroprotective effects of the free radical scavenger edaravone (MCI-186) in mice permanent focal brain ischemia. Brain Res 2004;1029(2):200–206.
   PubMed Web of Science ®Google Scholar
• Allen CL, Bayraktutan U. Oxidative stress and its role in the pathogenesis of ischaemic stroke. Int J Stroke 2009;4(6):461–70.
   PubMed Web of Science ®Google Scholar
• Valencia A, Moran J. Reactive oxygen species induce different cell death mechanisms in cultured neurons. Free Radic Biol Med 2004;36(9):1112–25.
   PubMed Web of Science ®Google Scholar
• Nishinaka Y, Mori H, Endo N, et al. Edaravone directly reacts with singlet oxygen and protects cells from attack. Life Sci 2010;86(21–22):808–13.
   PubMed Web of Science ®Google Scholar
• Sommani P, Arai T, Yamashita K, et al. Effects of edaravone on singlet oxygen released from activated human neutrophils. J Pharmacol Sci 2007;103(1):117–20.
   PubMed Web of Science ®Google Scholar
• Chan PK. Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 2001;21(1):2–14.
   PubMed Web of Science ®Google Scholar
• Jiao L, Zhang J, Li Z, et al. Edaravone alleviates delayed neuronal death and long-dated cognitive dysfunction of hippocampus after transient focal ischemia in Wistar rat brains. Neuroscience 2011;182(1):177–83.
   PubMedGoogle Scholar
• Juan W, Watanabe K, Ma M, et al. Edaravone inhibits JNK-c-Jun pathway and restores anti-oxidative defense after ischemia-reperfusion injury in aged rats. Biol Pharm Bull 2006;29(4):713–18.
   PubMed Web of Science ®Google Scholar
• Na W, Xia Z, Tinghui Z, Yuyang Z. Evaluation of neurological examination and cognitive functional on experimental cerebral ischemia. J Shenyang Pharm University 2012;29(3): 242–46.
   Google Scholar
• Na W, Donghai H, Yuyang Z. Evaluation of sensorimotor function in experimental cerebral ischemia. Chinese Pharmacological Bullet 2010;26(11):1410–14.
   Google Scholar
• Ajmal A, Mohd Moshahid K, Hayate J, et al. Edaravone ameliorates oxidative stress associated cholinergic dysfunction and limits apoptotic response following focal cerebral ischemia in rat. Mol Cell Biochem 2012;367(1–2):215–25.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Tanaka M, Watanabe K, et al. Research and development of the free radical scavenger edaravone as a neuroprotectant. Yakugaku Zasshi 2004;124(3):99–111.
   PubMed Web of Science ®Google Scholar
• Perez-Gonzalez A, Galano A. OH radical scavenging activity of edaravone: mechanism and kinetics. J Phys Chem B 2010;115(5):1306–14.
   PubMed Web of Science ®Google Scholar
• Perez-Gonzalez A, Galano A. On the outstanding antioxidant capacity of edaravone derivatives through single electron transfer reactions. J Phys Chem B 2012;116(3):1180–88.
   PubMed Web of Science ®Google Scholar
• Nakagawa H, Ohyama R, Kimata A, et al. Hydroxyl radical scavenging by edaravone derivatives: efficient scavenging by 3-methyl-1-(pyridin-2-yl)-5-pyrazolone with an intramolecular base. Bioorg Med Chem Lett 2006;16(23):5939–42.
   PubMed Web of Science ®Google Scholar
• Xingmiao C, Hansen C, Mingjing X, Jiangang S. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury. Acta Pharmacol Sin 2013;34(1):67–77.
   PubMed Web of Science ®Google Scholar
• Godínez-Rubí M, Mayorquín AE, Ortuño-Sahagún D. Nitric oxide donors as neuroprotective agents after an ischemic stroke-related inflammatory reaction. Oxid Med Cell Longev 2013;2013(1):1–16.
   Google Scholar
• Conti A, Miscusi M, Cardali S, et al. Nitric oxide in the injured spinal cord: synthases cross-talk, oxidative stress and inflammation. Brain Res Rev 2007;54(1):205–18.
   PubMed Web of Science ®Google Scholar
• Toda N, Ayajiki K, Okamura T. Cerebral blood flow regulation by nitric oxide: recent advances. Pharmacol Rev 2009;61(1):62–97.
   PubMed Web of Science ®Google Scholar
• Contreras DL, Robles HV, Romo E, et al. The role of nitric oxide in the post-ischemic revascularization process. Pharmacol Ther 2006;112(2):553–63.
   PubMed Web of Science ®Google Scholar
• Yihan W, Xia Z, Tinghui Z, Yuyang Z. Application of transgenic mice to studies on oxidative stress mechanism of cerebral ischemia. Chin J of Comparative Med 2012;22:46–55.
   Google Scholar
• Cui X, Chopp M, Zacharek A, et al. Role of endothelial nitric oxide synthetase in arteriogenesis after stroke in mice. Neurosci 2009;159(2):744–50.
   PubMed Web of Science ®Google Scholar
• Gertz K, Priller J, Kronenberg G, et al. Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase–dependent augmentation of neovascularization and cerebral blood flow. Circ Res 2006;99(10):1132–40.
   PubMed Web of Science ®Google Scholar
• Hiroshi O, Togashi H, Jesmin S, et al. Temporal effects of edaravone, a free radical scavenger, on transient ischemia-induced neuronal dysfunction in the rat hippocampus. Eur J Pharmacol 2005;512(2–3):129–37.
   PubMed Web of Science ®Google Scholar
• Yuyang Z, Juan L, Xing S. Neuronic calcium channel and anti-cerebral ischemia effect of calcium antagonists. J Shenyang Pharm University 2007;24(6):380–84.
   Google Scholar
• Keun-Hwa J, Kon C, Soon Tae L, et al. Augmentation of nitrite therapy in cerebral schemia by NMDA receptor inhibition. Biochem Biophys Res Commun 2009;378(3):507–12.
   PubMed Web of Science ®Google Scholar
• Ming S, Yumei Z, Yi G, Chao X. Inhibition of nNOS reduces ischemic cell death through down-regulating calpain and caspase-3 after experimental stroke. Neurochem Int 2009;54(5–6):339–46.
   PubMed Web of Science ®Google Scholar
• Hisano K, Watanabe M, Morimoto Y. Protective effects of the free radical scavenger edaravone against glutamate neurotoxicity in nearly pure neuronal culture. J Anesth 2009;23(3):363–69.
   PubMed Web of Science ®Google Scholar
• Wu T, Xinsheng D, Wei W, Jin W. MCI-186 (3-Methyl-1-phenyl-2-pyrazolin-5-one) attenuated simulated ischemia/reperfusion injury in cultured rat hippocampal cells. Biol Pharm Bull 2006;29:1613–17.
   PubMed Web of Science ®Google Scholar
• Mian Z, Christie MW, Wenglang Y, Ping W. Microglial CD14 activated by iNOS contributes to neuroinflammation in cerebral ischemia. Brain Res 2013;1506(1):105–114.
   PubMedGoogle Scholar
• Masahiro B, Tetsuya M, Hideki K, et al. The radical scavenger edaravone prevents oxidative neurotoxicity induced by peroxynitrite and activated microglia. Neuropharmacology 2005;48(2):283–90.
   PubMed Web of Science ®Google Scholar
• Ning Z, Miki KK, Ryota T, et al. Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke 2005;36(10):2220–25.
   PubMed Web of Science ®Google Scholar
• Kono S, Deguchi K, Morimoto N, et al. Tissue plasminogen activator thrombolytic therapy for acute ischemic stroke in 4 hospital groups in Japan. J Stroke Cerebrovasc Dis 2013;22(3):190–96.
   PubMed Web of Science ®Google Scholar
• Kikuchi K, Kawahara K, Miyagi N, et al. Edaravone: A new therapeutic approach for the treatment of acute stroke. Med Hypotheses 2010;75:583–85.
   PubMed Web of Science ®Google Scholar
• Mayank C, Leszek K. MMP-9 inhibition: a therapeutic strategy in ischemic stroke. Mol Neurobiol 2014;49(1):563–73.
   PubMed Web of Science ®Google Scholar
• Guohua W, Zhenglin J, Yongcai L, et al. Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats. J Neurotrauma 2011;28(1):2123–34.
   PubMedGoogle Scholar
• Kenji I, Koji Y, Masato Y., et al. Effects of edaravone, a free radical scavenger, on serum levels of inflammatory biomarkers in acute brain infarction. J Stroke Cerebrovasc Dis 2012;21(2):102–107.
   PubMed Web of Science ®Google Scholar
• Violeta LP, Kentaro D, Toru Y, et al. Free radical scavenger edaravone administration protects against tissue plasminogen activator induced oxidative stress and blood brain barrier damage. Curr Neurovasc Res 2010;7(4):319–29.
   PubMed Web of Science ®Google Scholar
• Sergio A, Ángel C. Translational stroke research of the combination of thrombolysis and antioxidant therapy. Stroke 2011;4(7):1524–28.
   Google Scholar
• Sergio A, Anns M P, Angel C. Uric acid administration in patients with acute stroke: a novel approach to neuroprotection. Expert Rev Nrurotherapeutics 2008;8(2):259–70.
   PubMedGoogle Scholar
• Yoshida H, Yanai H, Namiki Y, et al. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev 2006;12(1):9–20.
   PubMedGoogle Scholar
• YuYo S, Yury MM, Dianer Y, et al. Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke. PLoS One 2014;9(6):1–12.
   Google Scholar
• Romanos E, Planas AM, Amaro S, Chamorro A. Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke. J Cerebr Blood F Met 2007;27(1):14–20.
   PubMed Web of Science ®Google Scholar
• Paul AL, Justin AZ. Ebselen, a seleno-organic antioxidant, is neuroprotective after embolic strokes in rabbits: synergism with low-dose tissue plasminogen activator. Stroke 2003;34(1):2013–2018.
   PubMedGoogle Scholar
• Deguchi K, Miyazaki K, Tian FF, et al. Modifying neurorepair and neuroregenerative factors with tPA and edaravone after transient middle cerebral artery occlusion in rat brain. Brain Res 2012;1436:168–77.
   PubMed Web of Science ®Google Scholar
• Lapchak PA, Zivin JA. The lipophilic multifunctional antioxidant edaravone (radicut) improves behavior following embolic strokes in rabbits: A combination therapy study with tissue plasminogen activator. Exp Neuro 2009;215(1):95–100.
   PubMed Web of Science ®Google Scholar
• Kono S, Deguchi K, Morimoto N, et al. Intravenous thrombolysis with neuroprotective therapy by edaravone for ischemic stroke patients older than 80 years of age. J Stroke Cerebrovasc Dis 2009;22(7):1175–83.
   Google Scholar
• Aliev G, Obrenovich ME, Reddy VP, et al. Antioxidant therapy in Alzheimer's Disease: theory and practice. Mini Rev Med Chem 2008;8(13):1395–06.
   PubMed Web of Science ®Google Scholar
• Fydrych A, Moir R D, Huang C, et al. Amyloid-targeted metal chelation, anti-oxidative stress, and antiinflammation as Potential Alzheimer's therapies. Currt Bioacti Compo 2008;4(3):140–49.
   Google Scholar
• Yufang Y, Kai G, Tuo M, et al. Protective effect of edaravone against Alzheimer's disease-relevant insults in neuroblastoma N2a cells. Neurosci Lett 2012;531(2):160–65.
   PubMed Web of Science ®Google Scholar
• Bing L, Dawei Y, Zhiying X. Edaravone prevents neurotoxicity of mutant L166P DJ-1 in Parkinson's disease. J Mol Neurosci 2013;51(2):539–49.
   PubMed Web of Science ®Google Scholar
• Shanshan Z, Guichun Y, Lijun C, et al. Neuroprotective effects of edaravone on cognitive deficit, oxidative stress and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats. Neurotoxicology 2013;38:136–45.
   PubMed Web of Science ®Google Scholar
• Hidefumi I, Reika W, Jianhua Z, et al. Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice. Exp Neurol 2008;213(2):448–55.
   PubMed Web of Science ®Google Scholar
• Yoshino H, Kimura A. Investigation of the therapeutic effects of edaravone, a free radical scavenger, on amyotrophic lateral sclerosis (Phase II study). Amyotroph Lateral Scler 2006;7(4):247–51.
   Web of Science ®Google Scholar
• Taniguchi M, Uchinami M, Doi K, et al. Edaravone reduces ischemia-reperfusion injury mediators in rat liver. J Surg Res 2006;137(1):69–74.
   PubMed Web of Science ®Google Scholar
• Okatani Y, Wakatsuki A, Enzan H, Miyahara Y. Edaravone protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat liver. Eur J Pharmacol 2003;465(1):163–70.
   PubMed Web of Science ®Google Scholar
• Takahashi G, Sakurai, M, Abe K, et al. MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia. Ann thorac Surg 2004;78(2):602–07.
   PubMed Web of Science ®Google Scholar
• Yamawaki M, Sasaki N, Shimoyama M, et al. Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit cardiomyocytes. Brit J Pharmacol 2004;142(3):618–26.
   PubMed Web of Science ®Google Scholar
• Hori K, Tsujii M, Iino T, et al. Protective effect of edaravone for tourniquet-induced ischemia-reperfusion injury on skeletal muscle in murine hindlimb. BMC Musculoskel Dis 2013;14:113.
   PubMedGoogle Scholar