Edaravone

Edaravone, a classical free-radical scavenger, is an organic substance capable of crossing the blood-brain barrier and offering protection to brain cells^[1]. Edaravone’s keto-enol tautomerism underpins its potent radical-scavenging activity, enabling Edaravone to neutralize both peroxyl radicals and peroxynitrite and thereby confer cell- and neuro-protective antioxidant effects^[2]. Edaravone can also be used to treat digestive diseases, including acute liver injury, liver fibrosis^[3].

In vitro, pretreatment with 500μM Edaravone to spiral ganglion neurons (SGNs) for 20min reversed glutamate-induced injury: cell numbers were restored, death was prevented, spindle morphology was preserved, and debris was cleared. When 500μM Edaravone was instead added at 2, 6, or 12h after the glutamate insult, protection declined with delay; administration within 2h (or sooner) gave maximal rescue, whereas later time points failed to reduce cell death effectively^[4]. Treating Hepa 1-6 hepatoma cells with Edaravone (1-100µM) for 24h under cystine deprivation dose-dependently suppressed cell death and markedly reduced lactate dehydrogenase (LDH) leakage^[5].

In vivo, in Sprague-Dawley rats subjected to middle cerebral artery occlusion (MCAO), intraperitoneal administration of Edaravone (3mg/kg) significantly reduced both infarct volume and post-ischemic hemorrhage, yielding a markedly lower hemorrhage-to-infarct ratio than in untreated controls (23.5% vs. 63.2%)^[6]. In seven-day-old Wistar rats, daily intraperitoneal Edaravone (20mg/kg) for 14 days starting at hydrocephalus induction attenuated astrocyte activation and conferred partial protection against apoptotic cell death^[7].

References:
[1] Huang M, Mo Y, Lei H, et al. Edaravone: A Possible Treatment for Acute Lung Injury. Int J Gen Med. 2024;17:3975-3986.
[2] Duranti E, Cordani N, Villa C. Edaravone: A Novel Possible Drug for Cancer Treatment?. Int J Mol Sci. 2024;25(3):1633.
[3] Lei H, Wang M, Huang M, et al. Edaravone in Digestive Diseases - A Narrative Review. Drug Des Devel Ther. 2025;19:5071-5084.
[4] Bai X, Zhang C, Chen A, et al. Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons. Neural Plast. 2016;2016:4034218.
[5] Homma T, Kobayashi S, Sato H, et al. Edaravone, a free radical scavenger, protects against ferroptotic cell death in vitro. Exp Cell Res. 2019;384(1):111592.
[6] Okamura K, Tsubokawa T, Johshita H, et al. Edaravone, a free radical scavenger, attenuates cerebral infarction and hemorrhagic infarction in rats with hyperglycemia. Neurol Res. 2014;36(1):65-69.
[7] Garcia CAB, Catalão CHR, Machado HR, et al. Edaravone reduces astrogliosis and apoptosis in young rats with kaolin-induced hydrocephalus. Childs Nerv Syst. 2017;33(3):419-428.

Edaravone是一种经典的自由基清除剂，作为有机小分子可穿越血脑屏障，为脑细胞提供保护^[1]。Edaravone的酮-烯醇互变异构特性使其能高效清除过氧自由基和过氧亚硝酸盐，从而发挥细胞及神经抗氧化保护作用^[2]。此外，Edaravone还可用于治疗包括急性肝损伤、肝纤维化在内的消化系统疾病^[3]。

在体外，提前用500μM的Edaravone处理螺旋神经节神经元（SGNs）20分钟，可完全逆转谷氨酸诱导的损伤：细胞数量恢复、死亡被抑制、梭形形态保持、碎片清除；若在谷氨酸损伤后2、6或12小时才给予500μM的Edaravone，则保护效果随延迟而减弱，2小时内（或更早）给药效果最好，更晚给药则无法有效减少细胞死亡^[4]。在胱氨酸剥夺条件下，用1-100μM的Edaravone处理Hepa 1-6肝癌细胞24小时，可剂量依赖性地抑制细胞死亡并显著减少乳酸脱氢酶（LDH）漏出^[5]。

在体内，大脑中动脉闭塞（MCAO）模型Sprague-Dawley大鼠腹腔注射Edaravone（3mg/kg）后，梗死体积和缺血后出血量均显著减少，出血/梗死比明显低于未处理对照（23.5% vs 63.2%）^[6]。在7日龄Wistar大鼠中，从脑积水诱导当天开始每日腹腔注射Edaravone（20mg/kg）连续14天，可显著抑制星形胶质细胞激活，并对凋亡性细胞死亡产生部分保护作用^[7]。